A Study of ALKS 3831 in Adults With Schizophrenia

A Phase 2, Randomized, Multicenter, Safety, Tolerability, and Dose-Ranging Study of Samidorphan, a Component of ALKS 3831, in Adults With Schizophrenia Treated With Olanzapine

This is a Phase 2, randomized, placebo-controlled multicenter study, which will be conducted in 2 parts. The study duration for each subject will be approximately 33 weeks and will include 25 study visits.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Samidorphan (Low Dose); Drug: Olanzapine; Drug: Samidorphan (Medium Dose); Drug: Samidorphan (High Dose); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 347
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Alkermes Investigational Site
  • Kazanlak, Bulgaria, 6100
    • Alkermes Investigational Site
  • Lovech, Bulgaria, 5500
    • Alkermes Investigational Site
  • Novi Iskar, Bulgaria, 1280
    • Alkermes Investigational Site
  • Pazardzhik, Bulgaria, 4400
    • Alkermes Investigational Site
  • Sofia, Bulgaria, 1606
    • Alkermes Investigational Site
  • Tserova Koria, Bulgaria, 8260
    • Alkermes Investigational Site
  • Varna, Bulgaria, 9020
    • Alkermes Investigational Site
  • Vratsa, Bulgaria, 3000
    • Alkermes Investigational Site
• Czechia
  • Brno-mesto, Czechia
    • Alkermes Investigational Site
  • Praha, Czechia
    • Alkermes Investigational Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Alkermes Investigational Site
  • California
    • Anaheim, California, United States, 92805
      • Alkermes Investigational Site
    • Costa Mesa, California, United States, 92626
      • Alkermes Investigational Site
    • Culver City, California, United States, 90230
      • Alkermes Investigational Site
    • Escondido, California, United States, 92025
      • Alkermes Investigational Site
    • Garden Grove, California, United States, 92845
      • Alkermes Investigational Site
    • National City, California, United States, 91950
      • Alkermes Investigational Site
    • Oakland, California, United States, 94612
      • Alkermes Investigational Site
    • Oceanside, California, United States, 92056
      • Alkermes Investigational Site
    • Orange, California, United States, 92868
      • Alkermes Investigational Site
    • Pico Rivera, California, United States, 90660
      • Alkermes Investigational Site
    • San Diego, California, United States, 92103
      • Alkermes Investigational Site
    • Torrance, California, United States, 90502
      • Alkermes Investigational Site
  • Connecticut
    • New Britain, Connecticut, United States, 06052
      • Alkermes Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Alkermes Investigational Site
  • Florida
    • Bradenton, Florida, United States, 34208
      • Alkermes Investigational Site
    • Fort Lauderdale, Florida, United States, 33308
      • Alkermes Investigational Site
    • Gainesville, Florida, United States, 32607
      • Alkermes Investigational Site
    • Kissimmee, Florida, United States, 34741
      • Alkermes Investigational Site
    • Leesburg, Florida, United States, 34748
      • Alkermes Investigational Site
    • Oakland Park, Florida, United States, 33334
      • Alkermes Investigational Site
    • Orlando, Florida, United States, 32810
      • Alkermes Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Alkermes Investigational Site
    • Decatur, Georgia, United States, 30030
      • Alkermes Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Alkermes Investigational Site
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Alkermes Investigational Site
    • Shreveport, Louisiana, United States, 71101
      • Alkermes Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Alkermes Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Alkermes Investigational Site
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Alkermes Investigational Site
    • Saint Louis, Missouri, United States, 63118
      • Alkermes Investigational Site
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Alkermes Investigational Site
    • Neptune, New Jersey, United States, 07754
      • Alkermes Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Alkermes Investigational Site
    • Mason, Ohio, United States, 45040
      • Alkermes Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Alkermes Investigational Site
    • Oklahoma City, Oklahoma, United States, 73116
      • Alkermes Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • Alkermes Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Alkermes Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Alkermes Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Alkermes Investigational Site
    • Austin, Texas, United States, 78754
      • Alkermes Investigational Site
    • Dallas, Texas, United States, 75231
      • Alkermes Investigational Site
    • Dallas, Texas, United States, 75243
      • Alkermes Investigational Site
    • DeSoto, Texas, United States, 75115
      • Alkermes Investigational Site
    • Houston, Texas, United States, 77007
      • Alkermes Investigational Site
    • Houston, Texas, United States, 77008
      • Alkermes Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Alkermes Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • Alkermes Investigational Site
    • Richland, Washington, United States, 99362
      • Alkermes Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 50 years, inclusive
• Body mass index (BMI) of 17-30 kg/m2, inclusive
• Diagnosis of schizophrenia that is clinically stable

Exclusion Criteria:

• Initiated 1st antipsychotic treatment within the past 12 months and/or has had symptoms lasting <2 years
• Current diagnosis of alcohol or drug use disorder, moderate or severe
• Clinically significant or unstable medical illness, condition, or disorder
• Pregnant or breastfeeding
• Significant changes in diet or exercise regimen or plans to join a weight management program during the study
• Opioid medications taken within 14 days and/or need to take opioid medication during the study period
• History of hypersensitivity to or intolerance of olanzapine
• Use of olanzapine, clozapine, mesoridazine, chlorpromazine, or thioridazine for more than 1 week during the past year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose; Olanzapine + low dose samidorphan tablets taken once daily	Drug: Samidorphan (Low Dose); Tablets taken once daily; Other Names: Low dose samidorphan (ALKS 33); Drug: Olanzapine; Tablets taken once daily
Experimental: Medium Dose; Olanzapine + medium dose samidorphan tablets taken once daily	Drug: Olanzapine; Tablets taken once daily; Drug: Samidorphan (Medium Dose); Tablets taken once daily; Other Names: Medium dose samidorphan (ALKS 33)
Experimental: High Dose; Olanzapine + high dose samidorphan tablets taken once daily	Drug: Olanzapine; Tablets taken once daily; Drug: Samidorphan (High Dose); Tablets taken once daily; Other Names: High dose samidorphan (ALKS 33)
Placebo Comparator: Placebo; Olanzapine + placebo tablets taken once daily	Drug: Olanzapine; Tablets taken once daily; Drug: Placebo; Tablets taken once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Total Positive and Negative Syndrome Scale (PANSS) Score	Change from baseline (Day 8) to Day 92 (end of study Part A). The PANSS is a 30-item scale measuring severity of schizophrenia symptoms. Symptom severity for each item is rated on a 7-point scale (1 = absent; 7 = extreme), and the total score is added together, with a minimum score of 30 and a maximum score of 210. A higher score indicates more severe symptoms, while a lower score indicates less severe symptoms.	Baseline (Day 8) to Day 92 (end of study Part A)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Body Weight (Kilogram) From Baseline to Day 92	Percent change from baseline (Day 8) to the end of Part A (Day 92)	Baseline (Day 8) to Day 92 (end of study Part A)
Absolute Change in Body Weight (kg) From Baseline to Day 92	Change from randomization (Day 8) to the end of Part A (Week 12; Day 92)	Baseline (Day 8) to Day 92 (end of study Part A)
Percentage of Subjects Exhibiting Significant Weight Gain at Day 92	Significant weight gain will include a >=5%, >= 7%, or >=10% gain in body weight from baseline (Day 8) to Day 92 (end of study Part A)	Baseline (Day 8) to Day 92 (end of study Part A)
Change in Clinical Global Impressions - Severity (CGI-S) From Baseline to Day 92	Change in CGI-S score from baseline (Day 8) to the end of Part A (Week 12; Day 92). The CGI-S is a 7-point scale intended to measure the severity of a patient's illness at the time of assessment. Scores range from 1 (normal) to 7(extremely ill), so a higher score is correlative to more severe illness.	Baseline (Day 8) to Day 92 (end of study Part A)

Collaborators and Investigators

• Sponsor: Alkermes, Inc.

Publications and helpful links

General Publications

• Martin WF, Correll CU, Weiden PJ, Jiang Y, Pathak S, DiPetrillo L, Silverman BL, Ehrich EW. Mitigation of Olanzapine-Induced Weight Gain With Samidorphan, an Opioid Antagonist: A Randomized Double-Blind Phase 2 Study in Patients With Schizophrenia. Am J Psychiatry. 2019 Jun 1;176(6):457-467. doi: 10.1176/appi.ajp.2018.18030280. Epub 2019 Mar 8.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 5, 2013
• First Submitted That Met QC Criteria: July 18, 2013
• First Posted (Estimate): July 19, 2013

Study Record Updates

• Last Update Posted (Actual): October 6, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Schizophrenia; Alkermes; Samidorphan; Olanzapine
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Narcotic Antagonists; Alcohol Deterrents; Olanzapine; Naltrexone; ALKS-33
• Other Study ID Numbers: ALK3831-302