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Introduction: Combining measures of key core domains (especially pain and function) into a composite endpoint that requires each patient to meet a threshold of improvement for each domain provides information on multiple aspects of osteoarthritis within individual patients. This pooled analysis of two phase 3 studies (NCT02697773, NCT02709486) explored single and composite endpoints for assessing within-patient improvement in knee or hip osteoarthritis symptoms following subcutaneous administration of tanezumab or placebo. Methods: Endpoints at week 16 included proportions of responders (C 30% improvement) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function, WOMAC Pain/Function composite, and weekly average pain; and patient acceptable symptom state (PASS) composite responders, minimal clinically important improvement (MCII) composite responders, IntroductionCombining measures of key core domains (especially pain and function) into a composite endpoint that requires each patient to meet a threshold of improvement for each domain provides information on multiple aspects of osteoarthritis within individual patients. This pooled analysis of two phase 3 studies (NCT02697773, NCT02709486) explored single and composite endpoints for assessing within-patient improvement in knee or hip osteoarthritis symptoms following subcutaneous administration of tanezumab or placebo.MethodsEndpoints at week 16 included proportions of responders (≥ 30% improvement) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function, WOMAC Pain/Function composite, and weekly average pain; and patient acceptable symptom state (PASS) composite responders, minimal clinically important improvement (MCII) composite responders, Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders, and sustained weekly average pain responders.ResultsPooled population comprised 1545 patients. Of patients who had a ≥ 30% improvement in WOMAC Pain and/or WOMAC Physical Function, 88.5% were WOMAC Pain/Function composite responders, 7.0% were WOMAC Pain (but not Function) responders, and 4.4% were WOMAC Function (but not Pain) responders. Of weekly average pain responders, 43.1% were PASS composite responders. Odds ratios (tanezumab 2.5 mg and 5 mg groups, respectively, vs placebo) were 1.75 and 1.86 (WOMAC Pain/Function composite responders), 1.41 and 1.65 (weekly average pain responders), 1.60 and 1.73 (PASS composite responders), 1.52 and 1.68 (MCII composite responders), 1.75 and 1.88 (OMERACT-OARSI responders), and 1.85 and 1.48 (sustained weekly average pain responders). Subgroup analyses suggested a greater magnitude of effect for patients with a knee index joint compared with hip on some endpoints.ConclusionResponders on single pain endpoints were in many cases also responders on function or composite endpoints. Separation of tanezumab from placebo was similar and consistent across single and composite endpoints.

AIM To assess the impact of pre-specified patient characteristics on efficacy and safety of subcutaneous tanezumab in patients with osteoarthritis (OA). METHODS Data were pooled from two (efficacy; N = 1545) or three (safety; N = 1754) phase 3 placebo-controlled trials. Change from baseline to week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and patient global assessment of OA (PGA-OA) scores was compared between tanezumab (2.5 and 5 mg) and placebo groups via analysis of covariance. Treatment-emergent adverse events (TEAEs) were summarised descriptively. Analyses were done in patient subgroups (men or women; age

The growing need for symptomatic treatment of post-traumatic neuropathic pain (PTNP) continues to be unmet. Studies evaluating the efficacy of pregabalin for reducing neuropathic pain following trauma and surgery yielded positive results over ≤ 8-week treatment. To assess the efficacy and tolerability of pregabalin over 3 months in patients with PTNP, a randomized, double-blind, placebo-controlled, parallel-group trial evaluated patients with PTNP at 101 centers in 11 countries—the longest, largest such trial. Adults diagnosed with PTNP were randomly assigned (1:1) to 15 weeks of pregabalin (flexibly dosed 150–600 mg/day) or matching placebo. Primary efficacy analysis was by mixed-model repeated measures comparing change from baseline to week 15 in weekly mean pain scores between active and placebo groups. Evaluable patients included 274 in the pregabalin group and 265 in the placebo group. Trauma was surgical in 49.6% of patients, non-surgical in the remainder. The primary efficacy analysis showed no statistically significant difference between pregabalin and placebo groups in the change from baseline to week 15 [mean difference, − 0.22 points (95% confidence interval, 0.54–0.10); p = 0.1823]. However, comparisons for key secondary outcome measures yielded p values

Background:Tanezumab is a monoclonal antibody directed against nerve growth factor. It is in development for the treatment of moderate to severe chronic pain associated with osteoarthritis (OA) in adult patients for whom other treatments are ineffective or not appropriate. Phase 3 clinical trials have demonstrated the efficacy of subcutaneous tanezumab versus placebo for pain and function outcomes over various timepoints. Largely similar change from baseline was demonstrated in an oral nonsteroidal anti-inflammatory drug (NSAID)-controlled study.1,2,3,4 The efficacy of some other OA therapies can be dampened in patients with depression, anxiety, or insomnia.5,6,7Objectives:A post-hoc analysis to explore the efficacy of subcutaneous tanezumab after 16 weeks treatment, as compared to oral NSAID, in patients with OA and a history of depression, anxiety, or insomnia at baseline.Methods:Subgroup analysis of data from a randomized, double-blind, double-dummy, active-controlled phase 3 study of subcutaneous tanezumab (2.5 mg or 5 mg every 8 weeks) vs twice daily oral NSAID in patients (≥18 years) with radiographically-confirmed moderate to severe hip or knee OA (Kellgren-Lawrence grade ≥2; NCT02528188).4 Co-primary efficacy endpoints were change from baseline to week 16 in Western Ontario and McMaster Universities OA Index (WOMAC*) Pain and Physical Function subscale scores (both ≥5/10 at randomisation; increasing score indicates increasing pain/disability), and Patient’s Global Assessment of OA (PGA-OA, ≥3/5 at randomisation; increasing score indicates poorer condition). Enrolled patients had a history of inadequate pain relief with acetaminophen; inadequate pain relief with/intolerance to/contraindication to tramadol or opioids; or an unwillingness to take opioids. Patients were on a stable dose of NSAID for ≥30 days before screening. Data are presented as least squares (LS) mean change from baseline to week 16 for the whole population and for subgroups of patients with/without a history of depression, anxiety, or insomnia at baseline. Exploratory statistical analysis was conducted by analysis of covariance. P values were not adjusted for multiplicity. This exploratory post-hoc analysis was not part of the pre-specified hypothesis testing plan or included in any sample size calculations; therefore, comparisons between treatment arms or patient subgroups should be interpreted with caution.Results:Overall, 2996 patients were randomized and received at least one dose of study treatment (subcutaneous tanezumab 2.5 mg: n=1002; subcutaneous tanezumab 5 mg: n=998; oral NSAID: n=996). In this population (comprising patients with or without a history of anxiety, depression or insomnia), all treatments were associated with notable and largely similar magnitude improvements in WOMAC Pain, WOMAC Physical Function, and PGA-OA at week 16 (Figure 1). Across treatment groups, differences in LS mean change from baseline in patients with and without a history of depression, anxiety or insomnia ranged between 0 - 0.34 for WOMAC Pain and Physical Function and 0 - 0.19 for PGA-OA.Conclusion:Patients with a history of depression, anxiety, or insomnia did not appear to experience dampened improvements in pain or function with tanezumab or NSAID, as compared to those without.References:[1]Schnitzer T, et al. JAMA. 2019;322(1):37-48;[2]Berenbaum F, et al. Ann Rheum Dis. 2020;79(6):800-10;[3]Schnitzer T, et al. Semin Arthritis Rheum. 2020;50(3):387-93;[4]Hochberg M, et al. Arthritis Rheumatol. In Press;[5]Sharma A, et al. Open Access Rheumatol. 2016;31(8):103-13;[6]Mallen C, et al. PLoS Med. 2017;14(4):e1002273;[7]Campbell C, et al. Arthritis Care Res. 2015;67(10):1387-96.Acknowledgements:Study sponsored by Pfizer and Eli Lilly and Company. Editorial support was provided by Jennifer Bodkin of Engage Scientific Solutions and funded by Pfizer and Eli Lilly and Company.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB, Theresa Mallick-Searle Speakers bureau: Allergan, Abbvie, Eli Lilly and Company, Salix, Consultant of: Pfizer, Eli Lilly and Company, Elizabeth Johnston Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Dominique Menuet Employee of: Pfizer, Ruoyong Yang Employee of: Pfizer, Robert J Fountaine Shareholder of: Pfizer, Employee of: Pfizer.

Background Limited information exists on the efficacy of pregabalin in Chinese patients with diabetic peripheral neuropathy (pDPN). Methods An 11-week, double-blind, placebo-controlled trial in Chinese pDPN patients randomized (1:1) to pregabalin 300 mg/day or placebo. Primary efficacy endpoint was change from baseline in mean daily pain score (0 = no pain;10 = worst possible pain). Secondary efficacy endpoints included overall weekly mean pain score, responder status, impression of change, pain intensity, and sleep. Subgroup analysis assessed change in pain in patients with severe (≥7) baseline pain. Adverse events (AEs) were reported. ClinicalTrials.gov Identifier:NCT01332149. Results In total, 620 patients were randomized and treated (313, pregabalin; 307, placebo). Improvement in mean pain score with pregabalin versus placebo was not significant (mean treatment difference –0.28;P=0.0559). Post-hoc sensitivity analyses, excluding one patient due to GCP non-compliance, showed pregabalin significantly improved mean pain score when excluding the patient (–0.30;P=0.0448) or the associated site (–0.38;P=0.0142). Pregabalin significantly improved overall weekly mean pain score (P=0.0164) and ≥50% responders at endpoint (P=0.0384). Improvement in ≥30% responders, impression of change, pain intensity, and sleep were not significant. In the severe subpopulation, pregabalin significantly improved mean pain score versus placebo (–0.79;P=0.0040). The most commonly reported AE was dizziness (9.6% vs 3.9% with placebo). Conclusions Pregabalin did not significantly improve the primary measure of pain. Significant reductions in mean pain score were observed when excluding the GCP–non-compliant patient or site and in the severe subpopulation. Pregabalin was well tolerated in Chinese pDPN patients.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1 month

To evaluate pregabalin's efficacy and safety versus placebo to reduce pain in patients with diabetic peripheral neuropathy (DPN) using a concomitant nonsteroidal anti-inflammatory drug.In a randomized, double-masked, 14-week, 2-period, crossover study, patients with painful DPN using a nonsteroidal anti-inflammatory drug for non-DPN-related pain received 150 to 300 mg/d pregabalin or placebo (period 1); 14-day washout; then, the opposite therapy (period 2). Endpoints included weekly change in DPN pain score, sleep interference, adverse events, and patient-reported outcomes.Patients with similar baseline characteristics were randomized (period 1) to 1 of the 2 following possible sequences: pregabalin→placebo (n=154) or placebo→pregabalin (n=147). Results of the primary efficacy measure, mean weekly DPN pain at endpoint, showed no significant difference between pregabalin and placebo. However, 1 sensitivity analysis (mixed-model repeated measures) found greater pain score reductions with pregabalin than placebo at weeks 2 to 4 and overall (all P0.05). One secondary endpoint analysis, mean treatment difference in DPN-related sleep interference, favored pregabalin over placebo (P=0.0009). Other sensitivity and secondary analyses were nonsignificant. Treatment-emergent adverse events were consistent with the known safety profile of pregabalin.Pregabalin (vs. placebo) showed overall improvements in sleep, pain reduction in 1 sensitivity analysis, and was well tolerated. Potential factors that may have confounded the ability to detect a treatment difference in DPN pain reduction (high placebo response, carryover effect, short washout period, or pregabalin dose) are discussed in the context of future studies.

Background:Tanezumab, a monoclonal antibody against nerve growth factor, was recently evaluated in an 80 week placebo and tramadol-controlled trial in patients with chronic low back pain (CLBP) and a history of inadequate response to standard-of-care analgesics (NSAIDs, opioids, etc). Primary endpoint was change in Low Back Pain Intensity (LBPI) at week 16 vs placebo. Key secondary endpoints were the proportion of patients with ≥50% improvement in LBPI at week 16, change in Roland Morris Disability Questionnaire score at week 16, and change in LBPI at week 2 (all vs placebo). Tanezumab 10mg met the primary and all key secondary endpoints. Tanezumab 5mg did not meet the primary endpoint, but improved 2 of 3 key secondary endpoints. Due to the primary endpoint result and the statistical gate-keeping approach to control for multiple comparisons, a conclusion of superiority over placebo could not be made for the 5mg dose.Objectives:To further characterize tanezumab’s effects on pain and function in this trial through analysis of Brief Pain Inventory-short form (BPI-sf) scores.Methods:Patients received placebo (n=406), subcutaneous (SC) tanezumab 5mg (every 8 weeks; n=407), SC tanezumab 10mg (every 8 weeks; n=407) or oral tramadol prolonged-release (100-300mg/day; n=605). Pre-specified secondary endpoints included BPI-sf worst pain, average pain, the overall pain interference index, and selected individual domains of the index (general activity, walking ability, sleep, and normal work). Least squares (LS) mean (standard error [SE]) changes from baseline in BPI-sf scores were compared between groups (unadjusted for multiplicity) at week 16 using an analysis of covariance model. Scores range from 0-10 with higher scores indicating greater pain severity or functional impairment.Results:LS mean (SE) differences from placebo for worst pain were -0.52 (0.19) for tanezumab 5mg (p≤0.01), -0.54 (0.19) for tanezumab 10mg (≤0.01), and -0.24 (0.17) for tramadol (p=0.17). LS mean (SE) differences from placebo for average pain were -0.37 (0.18) for tanezumab 5mg (p=0.04), -0.46 (0.18) for tanezumab 10mg (≤0.01), and -0.17 (0.16) for tramadol (p=0.29). LS mean (SE) differences from placebo for the pain interference index were -0.41 (0.18) for tanezumab 5mg (p=0.03), -0.58 (0.18) for tanezumab 10mg (≤0.01), and -0.15 (0.17) for tramadol (p=0.39). Effects of tanezumab were not statistically different (p>0.05) from tramadol for worst pain, average pain, and the pain interference index, with exception of the pain interference index for tanezumab 10mg (p=0.01). Mean dose of tramadol was 203mg/day at week 16.Tanezumab 10mg significantly (pConclusion:Tanezumab 5mg and 10mg significantly improved worst pain, average pain, and overall pain interference index scores vs placebo in patients with CLBP. Tanezumab 10mg also significantly improved the overall pain interference index vs tramadol. Tanezumab 5mg significantly improved most individual domains of the pain interference index vs placebo, while tanezumab 10mg significantly improved all domains assessed vs placebo and vs tramadol.Disclosure of Interests:John Markman Consultant of: Consultant: Trigemina, Editas Medicine, and Plasma Surgical; Advisory board: Clexio Biosciences, Flexion Therapeutics, Quark Pharmaceuticals, Quartet Medicine, Collegium Pharmaceutical, Purdue Pharma, Biogen, Novartis, Aptinyx, Nektar, Allergan, Grünenthal, Eli Lilly and Company, Depomed, Janssen Pharmaceuticals, Teva Pharmaceutical Industries, KemPharm, Abbott Laboratories, Plasma Surgical, Chromocell, Convergence Pharmaceuticals, Inspirion, Pfizer, Sanofi, Daiichi Sankyo, and Trevena; Data safety monitoring boards for Novartis and Allergan, Serge Perrot Consultant of: Grunenthal, Pfizer, Lilly, MSD, Sanofi, Menarini, Seiji Ohtori: None declared, Thomas Schnitzer Consultant of: Pfizer, Lilly, AstraZeneca, GSK, Said Beydoun Grant/research support from: Argenx, Catalyst Pharma, Mallinckrodt, Pfizer, UCB, Consultant of: Alexion, Akcea, Alnylam, CSL, Takeda, Mitsubishi Tanabe, Speakers bureau: Alexion, Akcea, Alnylam, CSL, Takeda, Mitsubishi Tanabe, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ruoyong Yang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Candace Bramson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Christine West Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ken Verburg Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

To summarize the efficacy and examine the safety and tolerability of pregabalin in patients with central neuropathic pain due to spinal cord injury (SCI).Data were pooled from two 12 to 16 week, placebo-controlled trials of pregabalin in patients with neuropathic pain due to SCI. Pain diaries were used to rate pain from 0 = no pain to 10 = worst possible pain. Efficacy measures included: mean change in pain from baseline to endpoint; duration adjusted average change (DAAC) in pain; the percentage of patients with ≥30% or ≥50% reductions in pain score from baseline to endpoint; and Patient Global Impression of Change (PGIC) score at endpoint. Adverse events (AEs) were also compared between treatment groups.In total 174 patients received placebo and 182 received pregabalin. Mean change in pain from baseline to endpoint was improved in the pregabalin group compared with placebo (placebo-adjusted difference = -0.79; 95% CI = -1.15, -0.43; p0.001; baseline-observation-carried-forward). DAAC in pain was improved in patients receiving pregabalin compared with placebo (p0.001). The percentage of patients achieving ≥30% and ≥50% reductions in pain from baseline to endpoint was greater in the pregabalin arm compared with placebo (placebo: 30% = 22.5%, 50% = 11.6: pregabalin 30% = 35.6%, 50% = 22.4%) (all p0.01). PGIC scores at endpoint were significantly better in the pregabalin arm compared with placebo (p0.05). Treatment-related AEs, most commonly somnolence, dizziness, dry mouth, fatigue, edema, blurred vision, and constipation occurred more frequently in patients treated with pregabalin than placebo. The majority of AEs were mild to moderate in severity.Pregabalin reduced neuropathic pain due to SCI over a 12 to 16 week treatment period. Treatment-related AEs were mostly mild to moderate in severity and are consistent with the known safety profile of pregabalin. These findings should not be extrapolated to longer durations of treatment or other patient populations.

To assess efficacy and safety of once-daily controlled-release (CR) formulation of pregabalin in patients with postherpetic neuralgia.An enriched enrollment, randomized withdrawal trial, with 6-week single-blind pregabalin treatment phase and 13-week double-blind phase, where patients with ≥50% decrease in mean pain score at single-blind end point from baseline were randomized (1:1) to pregabalin CR (82.5 to 660 mg/d) or placebo. Primary efficacy outcome was time to loss of therapeutic response (LTR) (30% decrease in weekly mean pain score from single-blind baseline or discontinuation due to adverse event or lack of efficacy). Secondary efficacy outcomes included change in weekly mean pain score (1-wk recall period) at double-blind end point.In total, 801 patients were randomized and treated in the single-blind phase, and 413 in the double-blind phase (208, pregabalin CR; 205, placebo). Pregabalin CR significantly increased time to LTR versus placebo (Kaplan-Meier analysis) with significantly fewer LTR events with pregabalin CR than with placebo (29 [13.9%] vs. 63 [30.7%]; P0.0001). Median time to LTR was not estimable. Pregabalin CR significantly improved weekly mean pain score versus placebo: LS mean difference (95% CI) of -1.11 (-1.47, -0.75) and -1.00 (-1.34, -0.65) (P0.0001) from single-blind baseline and double-blind baseline, respectively. Most commonly reported adverse events in the single-blind phase were dizziness, somnolence, and peripheral edema. Pregabalin CR was well tolerated.Time to LTR was significantly longer with pregabalin CR than with placebo. Safety profile of pregabalin CR was comparable to that reported for the immediate-release formulation in patients with postherpetic neuralgia.

Limited information exists regarding the efficacy of pregabalin in Chinese patients with painful diabetic peripheral neuropathy (pDPN).An 11-week double-blind placebo-controlled trial was performed in Chinese pDPN patients randomized (1 : 1) to 300 mg/day pregabalin or placebo. The primary outcome was change from baseline to endpoint in mean pain score (MPS; 0, no pain; 10, worst possible pain; using the mean of the last seven daily pain scores). Secondary outcomes included weekly MPS and responder status (MPS reduced by ≥30% or ≥50% vs baseline). Subgroup analysis assessed patients with severe (≥7) baseline MPS. Adverse events (AEs) were reported.In all, 620 patients were randomized (pregabalin, n = 313; placebo, n = 307). Improvement in MPS with pregabalin versus placebo was not significant (P = 0.0559). Post hoc sensitivity analyses, excluding one patient/site due to Good Clinical Practice (GCP) non-compliance, showed pregabalin significantly improved MPS when excluding the patient (P = 0.0448) or site (P = 0.0142). Pregabalin significantly improved weekly MPS (P = 0.0164) and ≥50% responders at endpoint (P = 0.0384). Improvement in proportion of ≥30% responders, impression of change, pain intensity, and sleep did not differ significantly between the treatment groups. In the severe pDPN subpopulation, pregabalin significantly improved MPS versus placebo (P = 0.0040). The most commonly reported AE was dizziness (9.6% vs 3.9% with placebo).Pregabalin did not significantly improve the primary measure of pain in the trial. Significant reductions in MPS were observed when excluding the GCP non-compliant patient/site and in the severe pDPN subpopulation. Pregabalin was well tolerated in Chinese pDPN patients.

When designing a phase III superiority trial, we often compute the sample size to detect a treatment effect observed in a previous trial. In this article, we propose to take into account uncertainties around the estimated treatment effect and the estimated variability in patients’ responses jointly. We argue that it will be better to base the sample size decision for a confirmatory trial on the probability that the trial will produce a positive outcome than the traditional statistical power. We show that sample sizes computed under the traditional method are often too small to yield a desirable success probability. We extend this argument to the “conditional probability” concept that is often the basis for futility decision and sample size reestimation in an adaptive design. We argue that in the latter case, the concept of predictive power is likely to provide a more realistic measure on the prospect of the trial. In our opinion, a trialist should be concerned when the required sample size for a confirmat...

Higher dose ziprasidone has been associated with improved treatment outcomes in patients with schizophrenia or schizoaffective disorder. This study examines the relationship of ziprasidone dose and all-cause discontinuation in randomized clinical trials in patients with an acute exacerbation of schizophrenia or schizoaffective disorder.Data were analyzed for the first 28 days from 4 pivotal, randomized, double-blind, fixed-dose ziprasidone trials. Patients in these trials had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder where ziprasidone was administered twice daily with food. Data were analyzed to examine the association between ziprasidone dose and all-cause discontinuation due to lack of efficacy, adverse events, or because of other reasons, relative to placebo. Differences in discontinuation were evaluated using Cox proportional hazard models and number needed to treat (NNT).All-cause discontinuation for ziprasidone ranged from a low of 26.9% for the 160 mg/d dose group, to 40.9% for the 40 mg/d and 45.5% for the 80 mg/d groups, compared with 49.5% for placebo. The NNTs for avoiding 1 additional all-cause discontinuation compared with placebo were 12 (40 mg/d; n=186), 25 (80 mg/d; n=154), 9 (120 mg/d; n=125), and 4 (160 mg/d; n=104). The 120 mg/d and 160 mg/d groups were the only ziprasidone regimens associated with significantly lower all-cause discontinuation rates versus placebo in both the survival analysis (p=0.031 and0.0001, respectively) and in examination of the NNT. The 160 mg/d group was associated with lower all-cause discontinuation rates versus lower-dose ziprasidone regimens (p=0.0158 for versus 40 mg/d, p=0.002 for versus 80 mg/d). Efficacy accounted for 51% of all medication discontinuations across ziprasidone groups, compared with 62% for placebo. Findings for overall discontinuation due to lack of efficacy are consistent with results for all-cause discontinuation.Consistent with previous reports, higher doses of ziprasidone (120-160 mg/d, dosed twice daily with meals) are associated with significantly lower all-cause discontinuation rates and more favorable NNTs versus placebo. This was primarily driven by lower rates of discontinuation due to lack of efficacy.

Introduction:The long-term efficacy and tolerability of treatment with ziprasidone following a switch from prior antipsychotics was evaluated in outpatients with schizophrenia or schizoaffective disorder in three open-label, flexible-dose, 1-year extension studies.Methods:These studies enrolled completers of 6-week trials in which subjects were switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone. Identical study designs and the small number of patients entering the extensions supported pooling of the data.Results:Of 185 pooled subjects entering the extension studies, 72 completed 58 weeks of treatment. Median treatment duration was 34.6 weeks; median dose was 120 mg/day at endpoint. The intent-to-treat population showed significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores (−4.3 [P≤.01]), PANSS negative scores (−2.4 [P≤.0001]), and Clinical Global Impression of severity score (−0.3 [P≤.001]). Completers showed significant improvement in mean PANSS total scores (−10.2 [PPPPConclusion:Ziprasidone was well tolerated, and patients demonstrated significant improvement in metabolic parameters and in all movement disorder assessments. Insomnia and somnolence were the only adverse events with an incidence >10% in pooled subjects. No subject had a corrected QT interval ≥500 msec.

To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone, three 52-week, open-label extension studies of ziprasidone in outpatients (N=185) with schizophrenia or schizoaffective disorder successfully completing one of three, 6-week switch studies were carried out. Pre-switch treatment consisted of risperidone (n=43), olanzapine (n=71), or conventional antipsychotic agents (n=71). The maximum length of exposure to ziprasidone was 58 weeks. Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6, 19, 32, 45, and 58. Weight was measured at baseline and during each follow-up visit; height was recorded at baseline for the purpose of body mass index (BMI) calculation. Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global Impression-Severity scale which were obtained at baseline and major follow-up points. Clinically significant sustained improvements in weight, BMI, total cholesterol, and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine. Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters. Mean reductions in weight from baseline to study endpoint were 9.8 kg (p

Objective To explore time to first response and time to first persistent response of sertraline versus placebo and compare these parameters between children (6-11 years old, n = 177) and adolescents (12-17 years old, n = 199) with major depressive disorder. Method A 10-week placebo-controlled treatment was followed by a 24-week open-label sertraline treatment. The double-blind studies were not powered to detect efficacy differences between age groups. A post hoc analysis explored time to first response and first persistent response using the Children's Depression Rating Scale-Revised and Clinical Global Impressions-Improvement predefined criteria. Results There were no statistically significant differences in time to first response or first persistent response between sertraline and placebo in children, except for time to first response on Clinical Global Impressions-Improvement. Sertraline had a significantly faster time to first persistent response in adolescents compared to placebo. Within treatment groups, children had a significantly faster time to first response than adolescents, whether treated with placebo or sertraline, but not on time to first persistent response. Both age groups showed similar improvement over 34 weeks of treatment. Conclusion In the double-blind studies, children and adolescents had different patterns of response with sertraline vs. placebo. J. Am. Acad. Child Adolesc. Psychiatry , 2006;45(10):1162-1170.

Clinical trials of social anxiety disorder (SAD) have largely focused on the effect of treatment on symptoms of fear and avoidance, while neglecting the third clinically relevant dimension, physiological arousal. Data were combined from two previously reported placebo-controlled trials of sertraline in the treatment of moderate-to-severe generalized SAD. Efficacy was evaluated using the Brief Social Phobia Scale (BSPS). Three hundred forty-six subjects were randomized to 12-13 weeks of treatment with sertraline and 273 subjects to placebo. Following treatment, significant improvement was noted in favor of sertraline on the full BSPS (P < .001), as well as on each of the individual BSPS subscales: fear (P = .001); avoidance (P < .0001); and physiological arousal (P < .0001). Of the physiological symptoms assessed, the treatment advantage with sertraline was maintained for blushing (P < .003) and palpitations (P < .03), but not for trembling and sweating. These results confirm the efficacy of treatment with a selective serotonin reuptake inhibitor (SSRI), sertraline, across the spectrum of fear, avoidance, and physiological arousal in generalized SAD (GSAD). Among common physiological symptoms in this population, blushing and palpitations appear more treatment responsive than trembling and sweating to acute treatment with sertraline.

Neil K Singla,1 Jacques E Chelly,2 David R Lionberger,3 Joseph Gimbel,4 Luis Sanin,5 Jonathan Sporn,5 Ruoyong Yang,5 Raymond Cheung,5 Lloyd Knapp,6 Bruce Parsons5 1Lotus Clinical Research, Pasadena, CA, USA; 2Division of Acute Interventional Perioperative Pain, Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 3Department of Orthopedic Surgery, Baylor College of Medicine, Houston, TX, USA; 4Arizona Research Center, Phoenix, AZ, USA; 5Pfizer Inc., New York, NY, USA; 6Pfizer Inc., New London, CT, USA Purpose: To evaluate the efficacy and safety of pregabalin (150 or 300 mg/d) as an adjunctive therapy for the treatment of postoperative pain. Patients and methods: This study reports findings from three separate, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive pregabalin for the treatment of postoperative pain. Patients underwent one of three categories of surgical procedures (one procedure per study): elective inguinal hernia repair (post-IHR); elective total knee arthroplasty (post-TKA); or total abdominal hysterectomy (posthysterectomy). The primary endpoint in each trial, mean worst pain over the past 24 hours, was assessed 24 hours post-IHR and posthysterectomy, and 48 hours post-TKA. Patients rated their pain on a scale from 0 to 10, with higher scores indicating greater pain severity. Results: In total, 425 (post-IHR), 307 (post-TKA), and 501 (posthysterectomy) patients were randomized to treatment. There were no statistically significant differences between the pregabalin and placebo groups with respect to the primary endpoint in any of the three trials. The least squares mean difference in worst pain, between 300 mg/d pregabalin and placebo, was -0.7 (95% confidence interval [CI] =-1.4, -0.1; Hochberg adjusted P=0.067) post-IHR; -0.34 (95% CI =-1.07, 0.39; P=0.362) post-TKA; and -0.2 (95% CI =-0.66, 0.31; P=0.471) posthysterectomy. Conclusion: There were no significant differences between pregabalin and placebo with respect to the primary pain intensity measure in each of the three clinical trials. These studies encompass a large dataset (1,233 patients in total), and their results should be considered when assessing pregabalin's effectiveness in postoperative pain. Further studies are required to determine the potential pain-reducing benefit of pregabalin in the postoperative setting. Keywords: arthroplasty, herniorrhaphy, hysterectomy, postoperative pain, pregabalin

Objective: To assess the efficacy and tolerability of pregabalin for the treatment of central neuropathic pain after spinal cord injury (SCI). Methods: Patients with chronic, below-level, neuropathic pain due to SCI were randomized to receive 150 to 600 mg/d pregabalin (n = 108) or matching placebo (n = 112) for 17 weeks. Pain was classified in relation to the neurologic level of injury, defined as the most caudal spinal cord segment with normal sensory and motor function, as above, at, or below level. The primary outcome measure was duration-adjusted average change in pain. Key secondary outcome measures included the change in mean pain score from baseline to end point, the percentage of patients with ≥30% reduction in mean pain score at end point, Patient Global Impression of Change scores at end point, and the change in mean pain-related sleep interference score from baseline to end point. Additional outcome measures included the Medical Outcomes Study–Sleep Scale and the Hospital Anxiety and Depression Scale. Results: Pregabalin treatment resulted in statistically significant improvements over placebo for all primary and key secondary outcome measures. Significant pain improvement was evident as early as week 1 and was sustained throughout the treatment period. Adverse events were consistent with the known safety profile of pregabalin and were mostly mild to moderate in severity. Somnolence and dizziness were most frequently reported. Conclusions: This study demonstrates that pregabalin is effective and well tolerated in patients with neuropathic pain due to SCI. Classification of evidence: This study provides Class I evidence that pregabalin, 150 to 600 mg/d, is effective in reducing duration-adjusted average change in pain compared with baseline in patients with SCI over a 16-week period ( p = 0.003, 95% confidence interval = −0.98, −0.20).

We apply Bayesian approach, through noninformative priors, to analyze a Random Coefficient Regression (RCR) model. The Fisher information matrix, the Jeffreys prior and reference priors are derived for this model. Then, we prove that the corresponding posteriors are proper when the number of full rank design matrices are greater than or equal to twice the number of regression coefficient parameters plus 1 and that the posterior means for all parameters exist if one more additional full rank design matrix is available. A hybrid Markov chain sampling scheme is developed for computing the Bayesian estimators for parameters of interest. A small-scale simulation study is conducted for comparing the performance of different noninformative priors. A real data example is also provided and the data are analyzed by a non-Bayesian method as well as Bayesian methods with noninformative priors.

Two randomized, double-blind, placebo-controlled, 6-week studies comparing ziprasidone versus placebo for treatment of bipolar depression (BPD) failed to meet their primary study objectives, indicating that either ziprasidone is ineffective in the treatment of BPD or the study failed. Adult outpatients with bipolar I depression with 17-item Hamilton Rating Scale for Depression total score more than 20 at screening and baseline received either ziprasidone 40 to 80 mg/d, 120 to 160 mg/d, or placebo (study 1), or ziprasidone 40 to 160 mg/d or placebo (study 2). Primary efficacy measure in both studies was change from baseline in Montgomery-Asberg Depression Rating Scale total scores at week 6 (end of the study). Mixed-model repeated-measures methodology was used to analyze the primary efficacy measure in both studies. Secondary efficacy measures in both studies included Hamilton Rating Scale for Depression total score and Clinical Global Impression-Improvement score. Post hoc analyses were conducted for both studies to examine potential reasons for study failure. In both, ziprasidone treatment groups failed to separate statistically from placebo for change from baseline Montgomery-Asberg Depression Rating Scale score at week 6. Response rates were 49%, 53%, and 46% for placebo, ziprasidone 40 to 80 mg/d, and ziprasidone 120 to 160 mg/d, respectively (study 1), and 51% and 53% for placebo and ziprasidone 40 to 160 mg/d, respectively (study 2). Ziprasidone 40 to 160 mg/d did not show superiority over placebo at week 6 in the treatment of BPD. Post hoc analyses revealed serious inconsistencies in subject rating that may have limited the ability to detect a difference between drug and placebo response. Rating reliability warrants further investigation to improve clinical trial methodology in psychiatry.

The aim of this study was to evaluate the safety and efficacy of sertraline in children and adolescents who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for posttraumatic stress disorder (PTSD).Children and adolescents (6-17 years old) meeting DSM-IV criteria for PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200 mg/day) or placebo. The primary efficacy measure was the University of California, Los Angeles Post-Traumatic Stress Disorder Index for DSM-IV (UCLA PTSD-I).A total of 131 patients met entry criteria and were randomized to sertraline (n = 67; female, 59.7%; mean age, 10.8; mean UCLA PTSD-I score, 43.8 ± 8.5) or placebo (n = 62; female, 61.3%; mean age, 11.2; mean UCLA PTSD-I score, 42.1 ± 8.8). There was no difference between sertraline and placebo in least squares (LS) mean change in the UCLA PTSD-I score, either on a completer analysis (-20.4 ± 2.1 vs. -22.8 ± 2.1; p = 0.373) or on an last observation carried forward (LOCF) end point analysis (-17.7 ± 1.9 vs. -20.8 ± 2.1; p = 0.201). Attrition was higher on sertraline (29.9%) compared to placebo (17.7%). Discontinuation due to adverse events occurred in a 7.5% treated with sertraline and 3.2% treated with placebo.Sertraline was a generally safe treatment in children and adolescents with PTSD, but did not demonstrate efficacy when compared to placebo during 10 weeks of treatment. ClinicalTrials.gov Identifier: NCT00150306.

We compared the efficacy and safety of ziprasidone and aripiprazole in the treatment of acutely ill patients with schizophrenia. Patients were randomized to receive double-blind treatment with ziprasidone (80-160 mg/day), or aripiprazole (10-30 mg/day) for up to 4 weeks. Primary efficacy measures were the Clinical Global Impression of Severity scale (CGI-S) and Brief Psychiatric Rating Scale (BPRSd) total (derived from the Positive and Negative Syndrome Scale). Noninferiority for ziprasidone (N=125) relative to aripiprazole (N=128) was established for CGI-S score (P=0.007), but was not confirmed for BPRSd total score (P=0.248). Effect sizes for within-group improvement, however, were robust for both ziprasidone and aripiprazole (effect size range 1.0-1.1 for CGI-S; and range 1.1-1.2 for BPRSd total). A mixed model repeated measures analysis of BPRSd total score favored ziprasidone at day 4 compared with aripiprazole (P=0.04), with no significant differences between treatment groups at other visits (P=0.001 for interaction between treatment and visit). No statistically significant difference was found in CGI-S score between groups across all visits. Our findings suggest that ziprasidone and aripiprazole exhibit similar efficacy and tolerability profiles in the treatment of acute schizophrenia. Differences between the two drugs in the onset of therapeutic effect warrant further investigation.

Objective The pediatric version of the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) was developed to aid in the assessment of an important aspect of life experience in children and adolescents. Method The reliability and validity of the PQ-LES-Q was tested using data from a sample of 376 outpatient children (6-11 years old) and adolescents (12-17 years old) with major depressive disorder. Results The internal consistency coefficients at screening, baseline, and endpoint were high (0.87, 0.90, 0.89, respectively) as was the 1-week test-retest intraclass correlation coefficient of reliability (0.78). The correlations of the PQ-LES-Q total score with concurrent measures of severity of illness were in the moderate range (e.g., Global Clinical Impression of Severity, −0.40; Children's Global Assessment Scale, 0.36; Children's Depression Rating Scale total score, −0.45), as were the correlations with measures of change between baseline and endpoint (e.g., Clinical Global Impression of Severity, −0.34; Children's Global Assessment Scale, 0.33; Children's Depression Rating Scale total score, −0.45). Conclusions These findings support the use of the PQ-LES-Q as an additional measure of current clinical status and outcome because it taps dimensions that are not covered by the commonly used global severity of illness or symptomatic measures.

The aim of this study was to assess the long-term safety, tolerability, and efficacy of sertraline 50-200 mg once-daily in children (6-11 year olds) and adolescents (12-18 year olds) with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of major depressive disorder (MDD).This study consisted of a 24-week open-label observational study of children and adolescents who had completed either of two 10-week double-blind, placebo-controlled trials. The Children's Depression Rating Scale-Revised (CDRS-R) was the primary measure of efficacy.Two hundred ninety nine (299) patients completed the acute studies and were eligible for the extension study. Of these, 226 enrolled, but 5 did not receive treatment. Of 221 patients (107 children and 114 adolescents), 62.4% completed the study. The endpoint mean daily dose was 109.9 mg/day. The mean decrease in CDRS-R score from double-blind baseline was 34.8 points (p0.001), with patients showing continued improvement in CDRS-R scores regardless of which treatment they received in the double-blind studies. At endpoint, 86% of patients met CDRS-R responder and 58% CDRS-R remitter criteria.Sertraline appears to be well tolerated and safe over 24 weeks of treatment in children and adolescents with MDD. Children and adolescents treated with sertraline appear to have increased improvement over that seen in the first 10 weeks of treatment. These findings need confirmation in placebo-controlled studies.

We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms. This multicentre, 12-week, double-blind study randomly assigned subjects with predominantly negative-symptom schizophrenia [i.e. Positive and Negative Syndrome Scale (PANSS) Negative Subscale score >or=6 points greater than Positive Subscale score] to ziprasidone (40-80 mg b.i.d.; n=60) or amisulpride (50-100 mg b.i.d.; n=63). The primary efficacy variable was the change from baseline in PANSS Negative Subscale score. Secondary efficacy variables included change in scores for PANSS Total, Global Assessment of Functioning, Brief Psychiatric Rating Scale derived from PANSS Total and Core, Clinical Global Impression (CGI)-Severity and CGI-Improvement. For the change in PANSS Negative Subscale score, a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline, with equivalence claimed if the lower limit of the 95% confidence interval of the ratio exceeded 0.60. Mean daily dose, adjusted for differential numbers of subjects and differential days between visits, was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects, evaluable subjects (subjects with >or=4 weeks of double-blind treatment and no protocol deviations) and completers in both treatment groups. Ziprasidone demonstrated efficacy comparable to amisulpride in improving negative symptoms and global psychopathology. The groups demonstrated comparable improvements in secondary efficacy variables. Both agents were generally well tolerated, with comparably low incidences of movement disorders. In subjects with negative symptom-prominent schizophrenia, ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity.

Objective: To examine the change in Framingham risk score (FRS) arising from short-term treatment with ziprasidone or olanzapine. Method: Hospitalized adults with a primary DSM-IV diagnosis of schizophrenia or schizo-affective disorder were randomly assigned to 6 weeks of double-blind treatment with ziprasidone or olanzapine from November 21, 1998 to September 28, 2000. Data on fasting lipid levels were collected at screening and endpoint, and blood pressure was measured at screening and baseline and weekly until week 6 of treatment (or last visit). FRS for patients aged ≥30 years was calculated using an algorithm derived from the Framingham Heart Study. Baseline-to-endpoint least-squares mean changes in age-adjusted FRS by gender were compared using analysis of covariance (baseline adjusted). Results: Men who received olanzapine demonstrated a mean increase in their total cholesterol levels (+18.5 mg/dL; N = 53) and low-density lipoprotein cholesterol levels (+13.0 mg/dL; N = 45), whereas men who received ziprasidone demonstrated a mean decrease in their total cholesterol levels (−8.5 mg/dL; N = 44) and low-density lipoprotein cholesterol levels (−7.2 mg/dL; N = 40) (p = .0006 and p = .004, respectively). Additionally, men who received olanzapine showed an increase in baseline FRS (+7.69%; N = 53), whereas men who received ziprasidone showed a decrease in baseline FRS (−11.06%; N = 42) (p = .09). In women, treatment differences in FSR numerically favored ziprasidone but were not statistically significant. Neither treatment had a significant effect on blood pressure. Conclusion: In short-term treatment, olanza-pine was associated with a significant worsening of lipid profile compared with ziprasidone, with a consequent increase in FRS versus ziprasidone. These findings, coupled with the significant weight gain in patients treated with olanzapine versus ziprasidone, warrant investigation in longer-term trials.

The efficacy, safety, and tolerability of selective serotonin reuptake inhibitors (SSRIs) in the treatment of adults with major depressive disorder (MDD) are well established. Comparatively few data are available on the effects of SSRIs in depressed children and adolescents.To evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD.Two multicenter randomized, double-blind, placebo-controlled trials were conducted at 53 hospital, general practice, and academic centers in the United States, India, Canada, Costa Rica, and Mexico between December 1999 and May 2001 and were pooled a priori.Three hundred seventy-six children and adolescents aged 6 to 17 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined MDD of at least moderate severity.Patients were randomly assigned to receive a flexible dosage (50-200 mg/d) of sertraline (n = 189) or matching placebo tablets (n = 187) for 10 weeks.Change from baseline in the Children's Depression Rating Scale-Revised (CDRS-R) Best Description of Child total score and reported adverse events.Sertraline-treated patients experienced statistically significantly greater improvement than placebo patients on the CDRS-R total score (mean change at week 10, -30.24 vs -25.83, respectively; P =.001; overall mean change, -22.84 vs -20.19, respectively; P =.007). Based on a 40% decrease in the adjusted CDRS-R total score at study end point, 69% of sertraline-treated patients compared with 59% of placebo patients were considered responders (P =.05). Sertraline treatment was generally well tolerated. Seventeen sertraline-treated patients (9%) and 5 placebo patients (3%) prematurely discontinued the study because of adverse events. Adverse events that occurred in at least 5% of sertraline-treated patients and with an incidence of at least twice that in placebo patients included diarrhea, vomiting, anorexia, and agitation.The results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD.

ContextThe efficacy, safety, and tolerability of selective serotonin reuptake inhibitors (SSRIs) in the treatment of adults with major depressive disorder (MDD) are well established. Comparatively few data are available on the effects of SSRIs in depressed children and adolescents.ObjectiveTo evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD.Design and SettingTwo multicenter randomized, double-blind, placebo-controlled trials were conducted at 53 hospital, general practice, and academic centers in the United States, India, Canada, Costa Rica, and Mexico between December 1999 and May 2001 and were pooled a priori.ParticipantsThree hundred seventy-six children and adolescents aged 6 to 17 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–defined MDD of at least moderate severity.InterventionPatients were randomly assigned to receive a flexible dosage (50-200 mg/d) of sertraline (n = 189) or matching placebo tablets (n = 187) for 10 weeks.Main Outcome MeasuresChange from baseline in the Children's Depression Rating Scale–Revised (CDRS-R) Best Description of Child total score and reported adverse events.ResultsSertraline-treated patients experienced statistically significantly greater improvement than placebo patients on the CDRS-R total score (mean change at week 10, –30.24 vs –25.83, respectively; P = .001; overall mean change, –22.84 vs –20.19, respectively; P = .007). Based on a 40% decrease in the adjusted CDRS-R total score at study end point, 69% of sertraline-treated patients compared with 59% of placebo patients were considered responders (P = .05). Sertraline treatment was generally well tolerated. Seventeen sertraline-treated patients (9%) and 5 placebo patients (3%) prematurely discontinued the study because of adverse events. Adverse events that occurred in at least 5% of sertraline-treated patients and with an incidence of at least twice that in placebo patients included diarrhea, vomiting, anorexia, and agitation.ConclusionThe results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD.

Introduction Improvements are needed in the management of cancer-induced bone pain (CIBP). The objective of this study was to assess the efficacy and safety of pregabalin compared with placebo in the adjunctive treatment of patients with moderate to severe CIBP who were receiving opioids. Methods In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, 152 adults diagnosed with a malignant, solid tumor with metastases to bone were randomized to flexible-dose pregabalin (100, 150, 300, or 600 mg/day) or placebo, as add-on to stable opioid analgesic therapy, which was optimized prior to the start of the study. The primary efficacy endpoint was the duration-adjusted average change (DAAC) from baseline in the daily worst pain at the reference site (measured by 11-point numeric rating scale [NRS]) during the fixed-dosage phase. The study was terminated early following an interim analysis that indicated an increase in sample size would be needed to satisfy statistical assumptions for the primary endpoint. Given the early termination of the study, only descriptive analyses were performed. Results The mean (standard deviation) DAAC from baseline in NRS score for the primary endpoint favored pregabalin treatment: −1.53 (1.81) in the pregabalin group and −1.23 (1.74) in the placebo group. Mean DAAC for average pain and sleep interference (NRS) also favored pregabalin. More patients treated with pregabalin reported improvement (“very much improved,” “much improved,” or “minimally improved”) based on Patient Global Impression of Change: 81.4% compared with 70.0% in the placebo group. Conclusion Data from this study indicate that pregabalin use may reduce metastatic bone pain. Due to the incomplete analysis, further study of pregabalin in the management of CIBP is required.