Study to evaluate the safety, tolerability and dosing of Samidorphan in Adults with Schizophrenia treated with Olanzapine

Conditions: Schizophrenia
MedDRA version: 17.0Level: LLTClassification code 10040706Term: Simple type schizophreniaSystem Organ Class: 100000004873
Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Registration Number: EUCTR2013-002193-45-CZ

Lead Sponsor: Alkermes Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 280

Inclusion Criteria

1. Subject is willing and able to provide informed consent; subject has signed the main informed consent form (ICF) before initiation of any study specific procedures
2. Subject is age 18 to 50 years, inclusive, at screening
3. Subject has a body mass index (BMI) of 17.0-30.0kg/m2, inclusive, at screening
4. Subject has a diagnosis of schizophrenia (based on Diagnostic and Statistical Manual of Mental Disorders [DSM] criteria) that is clinically stable as evidenced by both of the following:
• No hospitalizations for acute exacerbations of schizophrenia within 2 months before screening
• Clinical Global Impressions-Severity (CGI-S) score of =3 (mild) at screening and Visit 2
5. Subject has a total Positive and Negative Syndrome Scale (PANSS) score =80 at screening and Visit 2
6. Subject has stable positive symptoms, as shown by a score = 4 on PANSS for items related to delusion, hallucination, conceptual disorganization, and unusual thought content, at screening and Visit 2.
7. Subject currently resides in a stable residence or living arrangement, has been in this residence/living arrangement for at least 8 weeks prior to screening, and the residence/living arrangement is not anticipated to change during the study.
8. Subject agrees to maintain current level of fitness or exercise regimen for the duration of the study
9. Subject reports a stable body weight for at least 3 months prior to screening
(change =5%) and from screening to Visit 2 (change =1 kg)
10. Subject agrees to use an acceptable method of contraception for the duration of the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subject does not meet duration of illness eligibility requirements for one of the following reasons:
•Subject initiated first antipsychotic treatment within the past 12 months.
•Subject has had symptoms lasting <2 years
2. Subject presents with comorbid neuropsychiatric disorders including the following:
• Axis I (according to DSM criteria) diagnosis of schizoaffective disorder or bipolar disorder, or current major depressive disorder that is untreated and/or unstable. Current major depressive disorder that is treated and stable is not a criterion for exclusion.
• Clinically significant cognitive difficulties that could interfere with participation in the study
• Drug induced or toxic psychosis
• Any other psychiatric condition that could interfere with participation in the study
3. Subject has a diagnosis (based on DSM-5 criteria) of moderate or severe alcohol or drug use disorder currently or at any time during the 3 months prior to screening.
4. Subject poses a current suicide risk as confirmed by the baseline Columbia-Suicide Severity Rating Scale (C-SSRS) by a response of Yes” to question #4 or 5 with ideation or suicidal behavior occurring in the past year
5. Subject reports positive human immunodeficiency virus (HIV) status at screening
6. Subject has diabetes or meets any of the following criteria:
• Hemoglobin A1c (HbA1c) =6.5% at Visit 1,
• Fasting plasma glucose =126 mg/dL (7.0 mmol/L) at Visit 2,
• A random plasma glucose =200 mg/dL (11.1 mmol/L) at Visit 1.
7. Subject has a clinically significant or unstable medical illness, condition, would be anticipated to potentially compromise subject safety or adversely
evaluation of efficacy, including (but not necessarily limited to) the following:
• Clinically significant hypotension or hypertension not controlled by medical therapy
• Unstable thyroid dysfunction in the past 6 months or a TSH value outside of the normal range at screening
• Personal or family history of neuroleptic malignant syndrome
• Dyslipidemia, defined for this study as total cholesterol >280 mg/dL>500 mg/dL, at screening
• Inflammatory bowel disease or any other gastrointestinal (GI) disorder with weight loss, anorexia nervosa, bulimia nervosa, or binge eating
• Neurologic conditions including the following:
- History of seizure disorder or a condition associated with seizures
- History of brain tumor, subdural hematoma or other clinically significant neurological condition within the 12 months prior to screening
- Head trauma with loss of consciousness within the 12 months prior to screening
- Active acute or chronic central nervous system (CNS) infection
- Stroke within the 6 months prior to screening
8. Subject has a cardiac condition that might confound the results of the study or pose additional risk when administering the investigational agents to the subject or preclude successful completion of the study. Such conditions include the following:
• Clinically significant cardiac arrhythmia, cardiomyopathy, or cardiac conduction
defect, a history of myocardial infarction or unstable angina, or clinically significant ECG abnormality at Visit 1 or Visit 2.
• QT interval >450 msec for men and >470 msec for women, as corrected by the
Fridericia formula (QTcF), observed at Visit 1 or Visit 2.
9. Subject has a laboratory abnormality that would compromise the well-being of the subject, or has any of the following specific laboratory results at Visit 1 or Visit 2:
• Asparta

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate 3 doses of samidorphan co-administered with olanzapine (ALKS3831) in subjects with schizophrenia to: <br>(1) evaluate ALKS3831 as a treatment of schizophrenia; (2) assess the safety and tolerability of ALKS3831; (3)characterize the impact of samidorphan component of ALKS3831 on weight and other metabolic factors;Secondary Objective: NA;Primary end point(s): The primary endpoint is the absolute change in PANSS total score from randomization to the end of Part A..;Timepoint(s) of evaluation of this end point: AEs will be monitored continuously from the time the subjects signs the informed consent at every visit

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary efficacy endpoints include the following:<br> - Percent change in body weight <br> -Absolute change in body weight <br> -Proportion of subjects exhibiting signifficant weight gain (definitions of significant weight gain will include body weight gain greater than 7%)<br> - - Absolute change in CGI-S<br><br>Additional endpoints include the following:<br> - Change in waist circumference <br> - Change in IWQOL-Lite scales (physical function, self-esteem, sexual life, public distress and work) and total score<br> - Change in PSP<br> - Change in FCI<br> - Change in alcohol and drug use;Timepoint(s) of evaluation of this end point: The timepoints will be evaluated at each visit or on specified visits as per schedule of assessments (Part A and Part B)

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