Clinical Trials

Date: 2017-06-08

Type of information: Initiation of the trial

phase: 3

Announcement: initiation of the trial

Company: Alkermes (Ireland)

Product: ALKS 3831

Action mechanism:

• ALKS 3831, a proprietary drug compound for the treatment of schizophrenia, is the combination of ALKS 33, a potent opioid modulator, and the established antipsychotic agent, olanzapine. Weight gain is a common and clinically relevant side effect of atypical antipsychotic medications, and olanzapine has one of the highest incidences and greatest amounts of weight gain among the widely prescribed products in this class of drugs.1 The weight gain side effect from atypical antipsychotics may be associated with the onset or exacerbation of diabetes and dyslipidemia, which are known risk factors for cardiovascular disease and mortality.
• In preclinical models, an ALKS 3831 regimen was shown to mitigate olanzapine-induced weight gain without affecting olanzapine's ability to demonstrate efficacy in a standard preclinical model used to assess antipsychotic activity. In another preclinical study, ALKS 3831 was shown to attenuate olanzapine-induced weight gain and abdominal adipose accretion.

Disease: schizophrenia

Therapeutic area: CNS diseases - Mental diseases

Country: USA

Trial details:

• The ENLIGHTEN clinical development program for ALKS 3831 is comprised of two key studies: a study evaluating the antipsychotic efficacy of ALKS 3831 compared to placebo over four weeks and a study assessing weight gain with ALKS 3831 compared to olanzapine in patients with schizophrenia over six months. The program also includes supportive studies to evaluate the pharmacokinetic and metabolic profile of ALKS 3831, as well as long-term safety.
• ENLIGHTEN-1, the first of two key phase 3 studies in the ENLIGHTEN clinical development program for ALKS 3831, is a multinational, randomized, double-blind study designed to evaluate the antipsychotic efficacy of ALKS 3831 compared to placebo over four weeks in patients experiencing an acute exacerbation of schizophrenia. The study also includes a comparator arm of olanzapine, an established atypical antipsychotic agent with proven efficacy but also metabolic liabilities, including significant weight gain. (NCT02634346)
• ENLIGHTEN-2 is a multicenter, randomized, double-blind phase 3 study comparing weight gain of ALKS 3831 to olanzapine in approximately 540 patients with stable schizophrenia over six months. Safety and tolerability will also be evaluated in the study. All participants in the double-blind portion of the study will be eligible to continue in an open-label safety study of ALKS 3831 for an additional 12 months. The objective of the extension phase of the study is to assess the safety and long-term tolerability of once-daily, oral ALKS 3831. (NCT02694328 )
• The clinical data from the ENLIGHTEN-1 and ENLIGHTEN-2 studies, if successful, will form the basis of a New Drug Application (NDA) to be submitted to the  FDA for ALKS 3831 for the treatment of schizophrenia.

Latest news:

• • On June 8, 2017, Alkermes announced the initiation of ENLIGHTEN-Early, a supportive study in the ENLIGHTEN clinical development program for ALKS 3831. This study will evaluate the weight gain profile of ALKS 3831 over a 12-week treatment period compared to olanzapine in young adult patients with schizophrenia, schizophreniform or bipolar I disorder who are early in their illness. ALKS 3831 is designed to provide the strong antipsychotic efficacy of olanzapine and a differentiated safety profile with favorable weight and metabolic properties.
• • On May 1, 2017, Alkermes announced completion of patient enrollment in ENLIGHTEN-1, the first of two key phase 3 studies in the ENLIGHTEN clinical development program for ALKS 3831, an oral atypical antipsychotic drug candidate for the treatment of schizophrenia. Topline results from the study are expected in mid-2017.
• ENLIGHTEN-2, the second key study from the ENLIGHTEN development program for ALKS 3831, is ongoing and enrolling patients with data expected mid-2018.
• • On February 10, 2016, Alkermes announced the initiation of ENLIGHTEN-2, the second of two core phase 3 studies for ALKS 3831, an investigational, novel, oral atypical antipsychotic drug candidate designed to be a broad-spectrum treatment for schizophrenia. ENLIGHTEN-2 will evaluate the weight gain profile of ALKS 3831 in patients with schizophrenia over a six-month treatment period compared to olanzapine.
• • On December 16, 2015, Alkermes announced the initiation of  the ENLIGHTEN pivotal program for ALKS 3831. The ENLIGHTEN pivotal program for ALKS 3831 is comprised of two key studies. ENLIGHTEN-1, a multicenter, randomized, double-blind phase 3 study to evaluate the antipsychotic efficacy of ALKS 3831 compared to placebo over four weeks in approximately 390 patients experiencing acute exacerbation of schizophrenia, is now underway and enrolling patients. The study will also include an olanzapine comparator arm. ENLIGHTEN-2, a phase 3 study assessing weight gain with ALKS 3831 compared to olanzapine in patients with schizophrenia over six months, is expected to initiate in Q1 2016. The program will also include supportive studies to evaluate the pharmacokinetic and metabolic profile of ALKS 3831, as well as long-term safety. Alkermes expects to use safety and efficacy data from the ENLIGHTEN pivotal program to serve as the basis for a New Drug Application (NDA) to be submitted to the FDA, pending study results.

Is general: Yes