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Background Observational studies of switching from branded to generic formulations of the same drug substance often lack appropriate comparators for the subjects who switched. Three generic formulations were deemed equivalent to Concerta: an authorized generic (AG) identical except for external packaging, and two other generics (EG). Objective Compare the incidence of a combined endpoint (switching back to Concerta, changing the use of immediate release methylphenidate (MPH), stopping all long-acting methylphenidate, or starting a new medication) among people switched from Concerta to the AG versus the EG. Methods Cohort study from the Truven CCAE database of people aged 6 to 65 diagnosed with ADHD, treated with Concerta, and switched to the EG or to the AG formulation. Results In the EG arm 24.6% and in the AG arm 19.7% of subjects switched back to Concerta. The proportion of subjects meeting the combined endpoint was 39.5% in the EG arm, 32.9% in the AG arm, a crude risk ratio of 1.20 (95% CI 0.94, 1.54). After adjustment by propensity score stratification, the adjusted odds ratio (OR) was 1.23 (95% CI 0.90, 1.70). In an unplanned analysis using a different method of adjustment, the adjusted OR was 1.00 (95% CI 0.69, 1.44). Discussion This study did not detect a difference between the proportion of people who met the study endpoint in the two study arms, i.e. between those who switched to a generic formulation that was identical to Concerta except for external packaging and those who switched to the comparison generics. The high incidence of the combined endpoint in the AG arm demonstrates the need for an appropriate comparator in studies of this type. Trial registration ClinicalTrials.gov NCT02730572

This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of a new chewable, rapidly-disintegrating mebendazole (MBZ) 500 mg tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment. Pediatric patients (1–15 years; N = 295; from Ethiopia and Rwanda) excreting A. lumbricoides and/or T. trichiura eggs were enrolled. The study had a screening phase (3 days), a double-blind treatment phase (DBP, 19 days), and an open-label phase (OLP, 7 days). Patients received MBZ or placebo on day 1 of DBP and open-label MBZ on day 19 ± 2 after stool sample collection. Cure rates (primary endpoint), defined as species-specific egg count of 0 at the end of DBP, were significantly higher in the MBZ group than placebo for A. lumbricoides (83.7% [72/86; 95% CI: 74.2%; 90.8%] versus 11.1% [9/81; 95% CI: 5.2%; 20.1%], P < 0.001) and for T. trichiura (33.9% [42/124; 95% CI: 25.6%; 42.9%] versus 7.6% [9/119; 95% CI: 3.5%; 13.9%], P < 0.001). Egg reduction rates (secondary endpoint) were significantly higher in the MBZ group than placebo for A. lumbricoides (97.9% [95% CI: 94.4; 99.9] versus 19.2% [95% CI: −5.9; 41.5]; P < 0.001) and T. trichiura (59.7% [95% CI: 33.9; 78.8] versus 10.5% [95% CI: −16.8; 32.9]; P = 0.003). Treatment-emergent adverse events (TEAEs) in MBZ group occurred in 6.3% (9/144) of patients during DBP and 2.5% (7/278) during OLP. No deaths, serious TEAEs, or TEAEs leading to discontinuations were reported. A 500 mg chewable MBZ tablet was more efficacious than placebo for the treatment of A. lumbricoides and T. trichiura infections in pediatric patients, and no safety concerns were identified.

Background A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer’s disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome. Methods Randomized patients (N = 2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints. Results Overall, 496 (24.3 %) patients were memantine users and were older (mean (SD), 74.0 (8.76) vs 72.8 (8.76), p = 0.008), with lower MMSE scores (18.2 (4.16) vs 19.2 (4.02), p p n = 1549) were lower for galantamine (1.39) vs placebo-treated patients (4.15). In memantine users, mortality rates were similar for placebo-treated (4.49) and galantamine-treated patients (5.57). In memantine nonusers at 24 months, the decline in MMSE scores (effect size (95 % CI) 0.25 (0.14; 0.36)) and DAD scores (0.17 (0.06; 0.28)) from baseline was lower in galantamine patients vs placebo patients. The absence of these benefits in memantine users could not be explained by baseline age, MMSE, or DAD scores. Conclusion This post-hoc analysis shows that the beneficial effects of galantamine at 2 years post treatment were not observed in patients who had been placed on background memantine. The reasons for memantine treatment and the possibility of interaction between memantine and galantamine merit further investigation. Trial registration ClinicalTrials.gov NCT00679627. Registered 15 May 2008.

Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, Davis B, Richards HM. Neuropsychiatr Dis Trea. 2014;10:391–401. On page 393, Figure 1, “Maintenance period (month 6to 24)” should be “Maintenance period (month 4 to 24)”;“– Gal at stable dose (at least 18 mg/day) as achieved on day 84c” should be “– Gal at stable dose (at least 16 mg/day) as achieved on day 84c”. Read the original article

Klaus Hager,1 Alan S Baseman,2 Jeffrey S Nye,2 H Robert Brashear,2 John Han,2 Mary Sano,3 Bonnie Davis,4 Henry M Richards2 1Clinic for Medicine of the Elderly, Hannover, Germany; 2Janssen Research and Development, LLC, Raritan, NJ, USA; 3The Mount Sinai Medical Center, New York, NY, USA; 4Synaptec Inc., Palm Beach Gardens, FL, USA Background: Currently available treatments for Alzheimer's disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. Methods: In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the 'last observation carried forward' approach, in an analysis of covariance model. Results: In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (-2.14 [4.34]) compared with the galantamine group (-1.41 [4.05]) (P