Clinical Trials

Date: 2017-06-29

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in The Lancet Psychiatry

Company: Teva Pharmaceutical Industries (Israel)

Product: SD-809 - deutetrabenazine

Action mechanism:

• protein inhibitor/VMAT2 inhibitor. SD-809 (deutetrabenazine) is a small molecule inhibitor of vesicular monoamine 2 transporter, or VMAT2, that is designed to regulate the levels of dopamine in the brain. SD-809 is being developed for the treatment of chorea associated with Huntington’s disease. SD-809 (deutetrabenazine) is Auspex Pharmaceuticals's lead investigational product.
• SD-809 became part of Teva’s central nervous system (CNS) product portfolio with the acquisition of Auspex Pharmaceuticals in May 2015.
• The FDA granted Breakthrough Therapy Designation for SD-809 for the treatment of TD in November 2015

Disease: tardive dyskinesia

Therapeutic area: Neurological diseases - CNS diseases

Country: Czech Republic, Germany, Hungary, Poland, Slovakia, USA

Trial details:

• The AIM-TD was a phase III, randomized, double-blind, placebo-controlled, parallel group, fixed-dose study of 288 male and female adults with moderate to severe TD. All patients had a total motor AIMS = 6 at screening and were randomized at baseline in a 1:1:1:1 ratio to receive one of three fixed-dose regimens of deutetrabenazine (12 mg/day, 24 mg/day, 36 mg/day) or placebo. Patients underwent dose escalation during the initial 4 weeks, followed by an 8-week maintenance period and a 1-week washout. The purpose of this study is to determine whether fixed-doses of an investigational drug, SD-809 (deutetrabenazine), will reduce the severity of abnormal involuntary movements of tardive dyskinesia. (NCT02291861)

Latest news:

• • On June 29, 2017, Teva Pharmaceutical announced the publication of results from the Phase III study, AIM-TD (Addressing Involuntary Movements in Tardive Dyskinesia), in The Lancet Psychiatry. The study evaluated the safety, efficacy and tolerability of the investigational use of fixed-dose deutetrabenazine (SD-809) compared to placebo for the treatment of tardive dyskinesia (Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial).
• The AIM-TD study and publication was led by Principal Investigators Karen E. Anderson , M.D., Associate Professor of Psychiatry & Neurology at Georgetown MedStar University Hospital , and Hubert Fernandez , M.D., Professor of Neurology at the Center for Neurological Restoration at the Cleveland Clinic .
• • On September 22, 2016, Teva Pharmaceutical Industries announced SD-809 (deutetrabenazine) showed statistically significant results in the second Phase III registration trial studying the potential of SD-809 for the treatment of tardive dyskinesia (TD). These new results for the AIM-TD trial follow positive results from the ARM-TD trial announced in June 2015 . Both ARM-TD and AIM-TD were 12 week treatment studies.  . Teva expects to make a regulatory submission to the FDA by the end of 2016. In the AIM-TD trial, the primary endpoint was change in Abnormal Involuntary Movement Scale (AIMS) score from baseline to week 12 for three fixed doses of SD-809 as compared to placebo. Patients' abnormal movements were assessed by blinded central video rating. All doses improved AIMS scores compared to placebo and at week 12, the 24 mg and 36 mg dose groups of SD-809 demonstrated a significant change from baseline based on the modified intent-to-treat population. At week 12, the AIMS rating improved from baseline by -3.3 points for 36 mg (P=0.001), -3.2 points for 24 mg (P=0.003) and -2.1 for 12 mg (P=NS), compared to -1.4 in placebo. In addition to the primary endpoint, mean scores on the Clinical Global Impression of Change (CGI) improved by -0.5 for 36 mg (P=0.011) and by -0.6 for 24 mg (P=0.002) based on the modified intent-to-treat population. The CGI is a global assessment of the patient's abnormal movements made by the treating investigator. For the protocol-specified secondary endpoint of CGI, in which treatment success was defined as "much improved" or "very much improved" at Week 12 and missing data were counted as treatment failure, 24 mg was superior to placebo (P=0.014); the 36 mg dose was superior to placebo, but did not reach statistical significance (P=0.059). Teva will present a fuller analysis at a future medical meeting. During the 12-week treatment, SD-809 demonstrated a favorable safety and tolerability profile. The frequency of overall adverse events and adverse events leading to withdrawal were similar among all treatment groups. The safety profile of SD-809 was consistent with data from previously reported clinical trials.

Is general: Yes