The Effect of CORT118335 on Olanzapine-Induced Weight Gain

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

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.

Study Overview

• Status: Completed
• Conditions: Antipsychotic-induced Weight Gain
• Intervention / Treatment: Drug: Olanzapine; Drug: CORT118335; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2019
• Primary Completion (ACTUAL): March 13, 2020
• Study Completion (ACTUAL): March 25, 2020

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (ACTUAL): March 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2020
• Last Update Submitted That Met QC Criteria: April 24, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight Changes; Body Weight; Weight Gain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: CORT118335-852; 2019-000633-39 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No