Drug-Drug Interaction Study of Miricorilant (QSC300704)
Research type
Research Study
Full title
An Open-Label, Drug-Drug Interaction Study Designed to Evaluate the Potential Effect of Miricorilant on Cytochrome P450 2C8, 2C9, 3A4, Uridine-diphospho-glucuronosyltransferase 1A1 Enzyme Activity, and Breast Cancer Resistance Protein Activity Using Probe Substrates in Healthy Male and Female Subjects
IRAS ID
1007538
Contact name
Joseph Custodio
Contact email
Sponsor organisation
Corcept Therapeutics Incorporated
ISRCTN Number
ISRCTN10379288
Research summary
Research Summary:
The Sponsor is developing the test medicine, miricorilant, for the potential treatment of Antipsychotic-Induced Weight Gain (AIWG) and Non-Alcoholic Steatohepatitis (NASH). AIWG is the condition in which patients taking antipsychotic medications tend to gain weight. In addition to weight gain, antipsychotic medications increase insulin resistance thereby increasing the risk of patients developing cardiovascular disease (diseases that affect the heart and blood vessels). NASH develops from non-alcoholic fatty liver disease (NAFLD), which is a range of conditions caused by a build-up of fat in the liver and is usually seen in overweight or obese people. A healthy liver should contain little or no fat.
This one-part, healthy subject drug-drug interaction study aims to assess the pharmacokinetics (PK, what the body does to the drug) of five approved marketed medicines when given with and without the test medicine, miricorilant in fed conditions (with food). This study will take place at one non-NHS site and will consist of a single study period involving up to 30 healthy male or female (of non-childbearing potential) subjects, aged between 18 and 60. Subjects will be admitted in the evening of Day -1. Subjects will receive an oral dose of Repaglinide (0.5 mg tablet); Tolbutamide (500 mg tablet); Midazolam (2.5 mg oral solution); Dolutegravir (50 mg tablet); Rosuvastatin (10 mg tablet) on two occasions (on the mornings of Day 1 and Day 10). On the mornings of Day 4 to Day 12, subjects will receive 400 mg of miricorilant, as 8 x 50 mg tablets. Subjects will be discharged on Day 13 and will receive a follow-up phone call, 4 to 11 days post-final test medicine dose.
Subject’s blood and urine will be taken throughout the study for analysis of the test medicine and marketed medicines, as well as for their safety. Subjects are expected to be involved in this study for approximately 7 weeks from screening to the follow-up call.
Lay Results:
"The Sponsor for this study was Corcept Therapeutics Incorporated and the study was conducted by Quotient Sciences (a clinical research organisation) at their clinical unit in Nottingham, UK.
The study took place from 08 Sep 2023 until 15 Nov 2023.
We would like to take this opportunity to thank all study volunteers.
What was this study about?
The aim of this study was to find out how the test medicine (miricorilant) interacted with other (already approved) medicines (repaglinide, tolbutamide, midazolam, dolutegravir and rosuvastatin) when dosed together. This was done by comparing how the body processed the approved medicines after miricorilant had been taken on multiple days (to reach “steady state”, which is when the amount of medicine in the blood remains the same over a period of time), to when the approved medicines were taken alone (without miricorilant).This study was a drug-drug interaction study. These types of studies are used to learn more about how medicines interact with each other. For example, one medicine may stop another medicine from working properly. It is important to know this so that doctors can fully inform patients before prescribing the test medicine or allow doctors to switch to different medicines which will not be affected by the test medicine. Studies like this also help scientists to better understand how test medicines work.
Who took part in this study?
30 healthy volunteers (29 males and 1 female who was not able to have children) aged 22 to 60 years old took part in the study.How was this study done?
This was an open label, non-randomised study, which means that volunteers knew what they were being dosed with, and all volunteers received the same test medicine and approved medicines in the same order.Each volunteer took the approved medicines on Days 1 and 10 and took the test medicine every day for 9 days (Days 4 to 12). On Day 10, volunteers took the test and approved medicines at the same time. The medicines were taken as tablets (apart from midazolam, which was taken as a solution), with water and after a meal. Volunteers went home on Day 13, then came back to the clinic between Days 16 and 23 for safety checks.
Blood samples were collected whilst the volunteers were in the clinic to find out the amount of test and approved medicines in the body over time. The study staff also collected information about the volunteers’ health throughout the study.
What were the results of this study?
There was an interaction between the test medicine and 2 of the approved medicines. There was a large increase in the amount of repaglinide in the blood and a moderate increase in the amount of rosuvastatin in the blood when these approved medicines were taken with the test medicine (Day 10), compared to when the approved medicines were taken alone (Day 1).There did not appear to be a significant interaction between the test medicine and the other 3 approved medicines (dolutegravir, midazolam and tolbutamide).
The test medicine was well tolerated in the healthy volunteers when given alone and with the approved medicines.Did the participants have any unwanted effects?
Yes.
Overall, unwanted effects occurred in 20 out of the 30 volunteers.
All of the unwanted effects were mild, and most occurred after the test and approved medicines were taken together. Most of the unwanted effects were caused by the approved medicines.
5 volunteers had unwanted effects that may have been caused by the test medicine when taken alone (without the approved medicines) and 4 volunteers had unwanted effects that may have been caused by the test medicine when taken together with the approved medicines.
3 volunteers had unwanted effects that may have been caused by the approved medicines when taken alone (without the test medicine) and 14 volunteers had unwanted effects that may have been caused by the approved medicine when taken together with the test medicine.The most common unwanted effect thought to be caused by the test medicine was feeling tired (fatigue). The most common unwanted effects thought to be caused by the approved medicines were repaglinide and/or tolbutamide related hunger, fatigue and dizziness. These unwanted effects occurred when the test and approved medicines were taken together.
Where can I find more information about this study?
For more information about the study, go to www.isrctn.com and search for the ISRCTN number:
ISRCTN10379288."REC name
London - Hampstead Research Ethics Committee
REC reference
23/LO/0227
Date of REC Opinion
4 Sep 2023
REC opinion
Further Information Favourable Opinion