Safety and Tolerability of Selisistat for the Treatment of Huntington’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (S47.004)
Citation Manager Formats
Make Comment
See Comments

Abstract
OBJECTIVE: To evaluate safety and tolerability of selisistat over 12 weeks in patients with Huntington’s Disease (HD). BACKGROUND: Selisistat is a first-in-class SirT1 inhibitor shown to be safe and well tolerated in healthy volunteers and HD patients in short-term studies. DESIGN/METHODS: This was a double-blind, placebo-controlled, international multi-centre study of selisistat in individuals with Stage I-III HD. Participants (30-70 yrs) with genetically confirmed HD, a Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score of >=5 and a Total Functional Capacity >=5 were randomized (1:1:1) to selisistat 50 or 200 mg or placebo once daily for 12 weeks. Safety and tolerability were evaluated by monitoring adverse events, vital signs, ECG and laboratory safety data throughout the study. Blood sampling for pharmacokinetics and soluble mutant huntingtin levels were collected throughout. RESULTS: A total of 144 patients were randomized and 125 patients (87%) completed the study. There were 9 serious adverse events, three in each treatment group, including one death in the placebo group. The most common adverse events were reversible increases in liver function tests without accompanying increases in bilirubin. All of these occurred in the selisistat groups; while most of these increases were <3×ULN, three events were classified as serious. No clinically relevant changes in the UHDRS readouts were observed during the relatively short treatment period. Levels of soluble mutant huntingtin in peripheral blood mononuclear cells showed borderline statistically significant (p=0.058 , p=0.075) increases of similar magnitude at 12 weeks compared to placebo in the 50mg and 200mg groups respectively, that reverted to levels consistent with the placebo group at follow-up. CONCLUSIONS: Apart from increases in liver function tests in a subset of patients, selisistat was safe and well tolerated, and a trend for modulation of the levels of soluble mutant huntingtin was observed. Study supported by: Siena Biotech SpA.
Disclosure: Dr. Reilmann has received personal compensation for activities with Novartis, Siena Biotech, Neursearch Inc., Ipsen, Teva Neuroscience, Lundbeck, and Medivation. Dr. Reilmann has received personal compensation for activities with the Journal of Huntington's Disease. Dr. Reilmann has received research support from the High-Q-Foundation, the Cure Huntington's Disease Initiative Foundation, the Deutsche Forschungsgemeinschaft, and the European Huntington's Disease Network. Dr. Squitieri has nothing to disclose. Dr. Priller has nothing to disclose. Dr. Saft has received personal compensation for activities with Temmler Pharma as a speaker. Dr. Saft has received research support from Neurosearch, Novartis and Siena Biotech. Dr. Mariotti has nothing to disclose. Dr. Suessmuth has nothing to disclose. Dr. Nemeth has nothing to disclose. Dr. Tabrizi has nothing to disclose. Dr. Quarrell has nothing to disclose. Dr. Craufurd has nothing to disclose. Dr. Rickards has nothing to disclose. Dr. Rosser has nothing to disclose. Dr. Borje has nothing to disclose. Dr. Michaela has nothing to disclose. Dr. Angieszka has nothing to disclose. Dr. Fischer has nothing to disclose. Dr. Macdonald has nothing to disclose. Dr. Munoz-Sanjuan has nothing to disclose. Dr. Pacifici has received personal compensation for activities with Science Applications International Corp. as a consultant. Dr. Frost has nothing to disclose. Dr. Farmer has nothing to disclose. Dr. Landwehrmeyer has received personal compensation for activities with Siena Biotech SPA and AOP Orphan. Dr. Landwehrmeyer has received research support from the European Commission, CHDI Foundation, Medivation, NeuroSearch, Novartis, Medesis, and Amarin. Dr. Westerberg has nothing to disclose.
Thursday, May 1 2014, 1:00 pm-2:45 pm
- Copyright © 2014 by AAN Enterprises, Inc.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Nicole Sur and Dr. Mausaminben Hathidara
► Watch
Related Articles
- No related articles found.