A randomized,double‐blind,placebo‐controlled trial evaluating cysteamine in Huntington's disease

Background : Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease. Methods : Ninety‐six patients with early‐stage Huntington's disease were randomized to 1200 mg delayed‐release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed‐effects model for repeated measures was used to assess treatment effect, expressed as the least‐squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo. Results : At 18 months, the treatment effect was not statistically significant — least‐squares mean difference, ‐1.5 ± 1.71 (P = 0.385) — although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated. Conclusions : Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington's disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society     

A randomized,double‐blind,placebo‐controlled trial of pridopidine in Huntington's disease

We examined the effects of 3 dosages of pridopidine, a dopamine‐stabilizing compound, on motor function and other features of Huntington's disease, with additional evaluation of its safety and tolerability. This was a randomized, double‐blind, placebo‐controlled trial in outpatient neurology clinics at 27 sites in the United States and Canada. Two hundred twenty‐seven subjects enrolled from October 24, 2009, to May 10, 2010. The intervention was pridopidine, either 20 (n=56), 45 (n=55), or 90 (n=58) mg daily for 12 weeks or matching placebo (n=58). The primary outcome measure was the change from baseline to week 12 in the Modified Motor Score, a subset of the Unified Huntington's Disease Rating Scale Total Motor Score. Measures of safety and tolerability included adverse events and trial completion on the assigned dosage. After 12 weeks, the treatment effect (relative to placebo, where negative values indicate improvement) of pridopidine 90 mg/day on the Modified Motor Score was ?1.2 points (95% confidence interval [CI], ?2.5 to 0.1 points; P = .08). The effect on the Total Motor Score was ?2.8 points (95% CI, ?5.4 to ?0.1 points; nominal P = .04). No significant effects were seen in secondary outcome measures with any of the active dosages. Pridopidine was generally well tolerated. Although the primary analysis did not demonstrate a statistically significant treatment effect, the overall results suggest that pridopidine may improve motor function in Huntington's disease. The 90 mg/day dosage appears worthy of further study. Pridopidine was well tolerated. © 2013 International Parkinson and Movement Disorder Society     

A randomized,double‐blind,placebo‐controlled trial of camicinal in Parkinson's disease

Background : Delayed gastric emptying may impair l ‐dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l ‐dopa and symptoms of PD. Methods : Phase II, double‐blind, placebo‐controlled trial. Participants were randomized to receive camicinal 50 mg once‐daily (n = 38) or placebo (n = 20) for 7 to 9 days. Results: l ‐dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l ‐dopa concentration was reduced, indicating more rapid absorption of l ‐dopa. Camicinal resulted in significant reduction in OFF time (–2.31 hours; 95% confidence interval: –3.71, –0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS‐UPDRS score (–12.5; 95% confidence interval: –19.67, ‐5.29). Camicinal treatment was generally well tolerated. Conclusions : PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l ‐dopa. This study provides evidence of an improvement of the motor response to l ‐dopa in people with PD treated with camicinal 50 mg once‐daily compared with placebo, which will require further evaluation. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Efficacy,tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new‐onset epilepsy: A randomized double‐blind clinical trial

Purpose: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new‐onset epilepsy. Methods: Randomized, double‐blind, 28‐day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new‐onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure. Results: At day 28, the estimated seizure‐free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment‐related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047). Conclusion: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new‐onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new‐onset epilepsy requiring rapid treatment initiation.     

Lacosamide as adjunctive therapy for partial‐onset seizures: A randomized controlled trial

Purpose: To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day) as adjunctive treatment in patients with uncontrolled partial‐onset seizures taking one to three concomitant antiepileptic drugs (AEDs). Methods: This multicenter, double‐blind, placebo‐controlled trial randomized patients 1:2:1 to placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8‐week baseline period, patients began treatment with placebo or lacosamide 100 mg/day, were force‐titrated weekly (100 mg/day increments) to the target dose, and entered a 12‐week maintenance period. Results: A total of 405 patients were randomized and received trial medication. Most (82.1%) were taking two to three concomitant AEDs. Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention‐to‐treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p < 0.001; ITT). Patients randomized to lacosamide showed large reductions in secondarily generalized tonic–clonic seizures, with median percent reductions in seizure frequency of 59.4% for lacosamide 400 mg/day and 93.0% for lacosamide 600 mg/day compared to 14.3% for placebo, and responder rates of 56.0% and 70.2% compared to placebo (33.3%). Dose‐related adverse events included dizziness, nausea, and vomiting. Discussion: Adjunctive treatment with lacosamide 400 and 600 mg/day reduced seizure frequency for patients with uncontrolled partial‐onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy and tolerability; lacosamide 600 mg/day may provide additional benefit for some patients as suggested by secondary efficacy analyses, including response in patients with secondarily generalized tonic–clonic seizures.