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Purpose/aim: AbobotulinumtoxinA (Dysport®, Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA) is an acetylcholine release inhibitor and a neuromuscular blocking agent. The United States prescribing information for abobotulinumtoxinA previously indicated only one dilution for cervical dystonia: 500 U/1 mL. Clinical trial data supporting a larger volume with a 500 U/2 mL dilution would offer clinicians flexibility with injection volume to better meet patient needs., Materials and Methods: We conducted a 12-week, phase 3b, multicenter, randomized, double-blind, placebo-controlled trial (NCT01753310). Adult subjects with a primary diagnosis of cervical dystonia were randomized (2:1) to receive a single injection of either abobotulinumtoxinA, 500 U/2 mL dilution, or placebo. The primary efficacy endpoint was changed from baseline in Toronto Western Spasmodic Torticollis Rating Scale total score at Week 4., Results: A total of 134 subjects (abobotulinumtoxinA, n = 89; placebo, n = 45) were randomized (intent-to-treat population) and 129 (abobotulinumtoxinA, n = 84; placebo, n = 45) completed the Week 4 primary endpoint evaluation (modified intent-to-treat population). In the modified intent-to-treat population, subjects receiving abobotulinumtoxinA experienced significantly greater changes from baseline versus placebo on the primary endpoint (weighted overall treatment difference -8.3, P < 0.001). The most common treatment-emergent adverse events (TEAEs) were dysphagia, muscle weakness, neck pain and headache. Overall, TEAEs were consistent with those reported in the abobotulinumtoxinA prescribing information (1 mL dilution) for cervical dystonia patients., Conclusions: This trial provides evidence that a 500 U/2 mL dilution is an effective treatment for cervical dystonia and exhibits a safety profile consistent with the known safety profile of abobotulinumtoxinA.

Tremor is a common symptom of Parkinson's disease (PD). The underlying pathophysiology of parkinsonian rest tremor is not well understood. Rest tremor is less responsive to dopaminergic therapy than are symptoms of bradykinesia and rigidity. This paper reviews the effects of 1 mg daily oral rasagiline, as monotherapy and as adjunct therapy, on parkinsonian tremor. A literature search of the EMBASE database was conducted to identify relevant articles in English published between 2000 and October, 2012 using the search terms "rasagiline," or "Azilect®," or "Agilect®," and refined using the terms "Parkinson's disease" and "clinical trial." Of 22 identified publications, two large placebo-controlled trials of rasagiline monotherapy (TEMPO and ADAGIO) and two large placebo-controlled trials of rasagiline as adjunctive therapy with levodopa (PRESTO and LARGO) specifically evaluated the effect of rasagiline on tremor using the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. Prospective and post-hoc analyses from these phase III studies show rasagiline monotherapy significantly improved tremor symptoms in early PD, independent of disease duration, compared with placebo. In levodopa-treated patients with motor fluctuations who were already receiving optimized dopaminergic treatment, the addition of rasagiline adjunct therapy significantly improved tremor symptoms. Significant improvement was evident as early as 10 weeks from treatment initiation. Tremor symptoms also improved in a subset of patients with severe tremor when rasagiline was added to their existing PD treatment regimen. These data suggest that rasagiline used as monotherapy and as adjunctive therapy is effective for reducing tremor severity in patients with PD.

Objective: Assess motor function and quality of life (QoL) in Parkinson's disease (PD) subjects with end-of-dose wearing off (EODWO), comparing immediate and delayed switch (IS, DEL) to levodopa/carbidopa/entacapone (LCE)., Background: LCE treatment improves motor function in PD patients with EODWO. Correlations with QoL have not been previously assessed., Methods: A 16-week, prospective, randomized, multicenter, open-label study in PD subjects on stable levodopa/carbidopa (LC) doses with EODWO. The IS subjects switched to LCE at baseline; DEL subjects at week 4. The primary efficacy variable was UPDRS III score (baseline to week 4). QoL measurements (PDQUALIF, PDQ-39) were assessed at baseline, weeks 4, 8, and study endpoint., Results: The intent-to-treat population comprised 350/359 patients (IS, n = 177; DEL, n = 173). A significant decrease in UPDRS III scores at week 4 was observed (IS, 3.7U, p < .0001; DEL, 1.8U, p = .0018). Group differences favored IS (1.9U, p = .0148). At week 8, IS subjects had significant total score decreases in PDQUALIF (2.5U, p = .0133) and PDQ-39 (5.8U, p = .0001). In the mobility and activities of daily living PDQ-39 subdomains, IS subjects had significantly larger week 4 decreases (versus DEL p = .0331 and p = .0125, respectively). Adverse events included diarrhea (14.5%), nausea (12.3%), and dizziness (8.4%)., Conclusion: The IS provided greater motor improvement at week 4 and improved QoL at week 8.

Disease modification or slowing the progression of any neurodegenerative disorder represents a dire unmet need. There have been trials for several decades specifically designed to help evaluate whether a specific therapy might be able to slow the progression of Parkinson's disease (PD) or be disease modifying. Trials evaluating the use of coenzyme Q10, pramipexole, and levodopa suggest that these medications offer symptomatic benefit uniquely, while other studies reveal that rasagiline and selegiline may be disease modifying. This review will discuss in detail the design and results of clinical trials for varied medical therapies that were specifically undertaken to discern whether a particular treatment might be disease modifying in the treatment of PD.

This study was designed to follow the long-term efficacy, safety, and tolerability of rasagiline for Parkinson's disease (PD) with data collected from all patients who had ever taken rasagiline during the 12-month TEMPO monotherapy trial (N = 398) and subsequent open-label extension. Patients were followed for up to 6.5 years with a mean of 3.5 +/- 2.1 years. After 12 months, additional PD medications were added as required. Of patients remaining in the trial at 2 years, 46% were maintained on rasagiline monotherapy. The majority of patients received a dopamine agonist prior to levodopa as the first additional dopaminergic agent. Analysis using a Kaplan-Meier method indicated that by 5.4 years only 25% of patients progressed to Hoehn & Yahr stage III. Rasagiline was well tolerated, with 11.3% of patients (45/398) withdrawing because of an adverse event. Rasagiline therapy for PD was effective, well tolerated, and safe in this long-term trial.

Response rate (RR) and mean improvement (MI) in the pain subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-PS) from two placebo-controlled studies and one comparator-controlled study were evaluated to examine the effect of rimabotulinumtoxinB (BoNT-B) on cervical dystonia (CD) pain. Subjects receiving either of two doses of BoNT-B in the AN072-301 trial had an RR of 66% and 58% compared with 23% for placebo (p < .05). Subjects receiving BoNT-B in the AN072-302 trial had an RR of 49% compared with 19% for placebo (p < .05). Subjects receiving BoNT-B in the AN072-402 comparator-controlled trial had a significantly higher RR than those treated with BoNT-A (59% vs. 36%; p < .05). Additionally, subjects treated with BoNT-B in these placebo-controlled trials had significantly larger MIs than those treated with placebo (4.3 and 3.7 vs. 0.5 for AN072-301 and 3.6 vs. 0.1 for AN072-302; p < .05). Subjects treated with BoNT-B in the comparator-controlled trial demonstrated a numerically larger MI than those treated with BoNT-A (2.6 vs. 1.8; p = .1651). These results support the consideration of BoNT-B as an effective first-line botulinum toxin treatment for patients with CD who list pain as a primary complaint.