BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder, 
characterised by motor, cognitive, and behavioural deficits. Pridopidine belongs 
to a new class of compounds known as dopaminergic stabilisers, and results from 
a small phase 2 study in patients with Huntington's disease suggested that this 
drug might improve voluntary motor function. We aimed to assess further the 
effects of pridopidine in patients with Huntington's disease.
METHODS: We undertook a 6 month, randomised, double-blind, placebo-controlled 
trial to assess the efficacy of pridopidine in the treatment of motor deficits 
in patients with Huntington's disease. Our primary endpoint was change in the 
modified motor score (mMS; derived from the unified Huntington's disease rating 
scale) at 26 weeks. We recruited patients with Huntington's disease from 32 
European centres; patients were aged 30 years or older and had an mMS of 10 
points or greater at baseline. Patients were randomly assigned (1:1:1) to 
receive placebo, 45 mg per day pridopidine, or 90 mg per day pridopidine by use 
of centralised computer-generated codes. Patients and investigators were masked 
to treatment assignment. We also assessed the safety and tolerability profile of 
pridopidine. For our primary analysis, all patients were eligible for inclusion 
in our full analysis set, in which we used the last observation carried forward 
method for missing values. We used an analysis of covariance model and the 
Bonferroni method to adjust for multiple comparisons. We used a prespecified 
per-protocol population as our sensitivity analysis. The α level was 0·025 for 
our primary analysis and 0·05 overall. This trial is registered with 
ClinicalTrials.gov, number NCT00665223.
FINDINGS: At 26 weeks, in our full analysis set the difference in mean mMS was 
-0·99 points (97·5% CI -2·08 to 0·10, p=0·042) in patients who received 90 mg 
per day pridopidine (n=145) versus those who received placebo (n=144), and -0·36 
points (-1·44 to 0·72, p=0·456) in those who received 45 mg per day pridopidine 
(n=148) versus those who received placebo. At the 90 mg per day dose, in our 
per-protocol population (n=114), the reduction in the mMS was of -1·29 points 
(-2·47 to -0·12; p=0·014) compared with placebo (n=120). We did not identify any 
changes in non-motor endpoints at either dose. Pridopidine was well tolerated 
and had an adverse event profile similar to that of placebo.
INTERPRETATION: This study did not provide evidence of efficacy as measured by 
the mMS, but a potential effect of pridopidine on the motor phenotype of 
Huntington's disease merits further investigation. Pridopidine up to 90 mg per 
day was well tolerated in patients with Huntington's disease.
FUNDING: NeuroSearch A/S.