The Effect of CORT118335 on Olanzapine-Induced Weight Gain

Study Overview
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Brief Summary
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This study will investigate if there is any difference in the amount of weight gained by participants taking olanzapine with CORT118335 compared with olanzapine with placebo (a dummy test medicine which looks like CORT118335 but contains no active medicine). Safety and tolerability of CORT118335 when taken with olanzapine will also be evaluated.

Official Title
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A Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of CORT118335 on Olanzapine-Induced Weight Gain in Healthy Subjects

Conditions
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Antipsychotic-induced Weight Gain

Intervention / Treatment
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* Drug: Olanzapine
* Drug: CORT118335
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index 18.0 to 25.0 kg/m^2, inclusive Stable body weight as indicated by assessment at screening and pre-dose Able to swallow the size and number of tablets required Provide written informed consent and agree to adhere to study restrictions and contraception requirements. Exclusion Criteria: Have received any investigational medicine in a clinical research study within the previous 3 months, or CORT118335 at any time Employee, or immediate family member of a study site or Sponsor employee Have a pregnant partner History of abuse of any drug or alcohol, or regularly consume more than 21 units alcohol/week Smokers or users of e-cigarettes and nicotine replacement products within the last 6 months Clinically significant abnormal results of clinical laboratory safety tests, electrocardiogram, or measurement of heart rate and blood pressure History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, or gastrointestinal disease, neurological or psychiatric disorder History of jaundice or gallstones or had a cholecystectomy Family history or known risk for narrow angle glaucoma Consumed liquorice or other glycyrrhetic acid derivatives regularly in the past 6 months Any condition that could be aggravated by glucocorticoid and/or mineralocorticoid antagonism (e.g., asthma, any chronic inflammatory condition, postural hypotension/orthostatic symptoms) Presence or history of clinically significant allergy Donation or loss of greater than 400 mL of blood within the previous 3 months Are taking, or have taken, any prescribed or over-the-counter drug within 14 days other than paracetamol or standard dose multivitamins. Longer restrictions apply for some medicines. Lactose intolerance. NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine plus CORT118335<br>Participants will receive olanzapine 10 mg oral tablets and double-blind CORT118335 600 mg after breakfast once daily for 14 days. | Drug: Olanzapine<br>* Olanzapine 10 mg oral tablet<br>Drug: CORT118335<br>* CORT118335 600 mg oral tablets administered as 2 X 300 mg or 6 X 100 mg tablets<br>|
| Placebo Comparator: Olanzapine plus Placebo<br>Participants will receive olanzapine 10 mg oral tablets and double-blind placebo matching CORT118335 oral tablets after breakfast once daily for 14 days. | Drug: Olanzapine<br>* Olanzapine 10 mg oral tablet<br>Drug: Placebo<br>* Placebo matching CORT118335, 2 or 6 oral tablets, depending on the CORT118335 tablet strength available<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change from Baseline in Body Weight |  | Pre-dose on Day 1 (Baseline) and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with One or More Adverse Events |  | Up to Day 28 | 
| Percentage of Participants with One or More Serious Adverse Events |  | Up to Day 28 | 
| Percentage of Participants Discontinued from the Study due to an Adverse Event |  | Up to Day 28 | 
| Mean Change from Baseline in Glucose |  | Pre-dose on Day 1 (Baseline), pre-dose on Days 8, 15, and 28 | 
| Mean Change from Baseline in Insulin |  | Pre-dose on Day 1 (Baseline), pre-dose on Days 8, 15, and 28 | 
| Mean Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) |  | Pre-dose on Day 1 (Baseline), pre-dose on Days 8, 15, and 28 | 
| Mean Change from Baseline in Triglycerides |  | Pre-dose on Day 1 (Baseline), pre-dose on Days 8, 15, and 28 | 
| Mean Change from Baseline in Waist-to-Hip Ratio |  | Pre-dose on Day 1 (Baseline), Days 8, 15, and 28 | 
| Plasma Pharmacokinetics (PK) of CORT118335: Time from Dosing at which Maximum Concentration is Apparent (tmax) |  | Pre-dose and at pre-specified time points up to 24 hours after dosing on Day 7 | 
| Plasma PK of CORT118335: Maximum Observed Concentration (Cmax) |  | Pre-dose and at pre-specified time points up to 24 hours after dosing on Day 7 | 
| Plasma PK of CORT118335: Area Under the Concentration-Time Curve Over the Dose Interval (AUCtau) |  | Pre-dose and at pre-specified time points up to 24 hours after dosing on Day 7 |