Clinical trial NCT04795479: T/QT Study to Investigate the Effect of Relacorilant on Cardiac Repolarization in Healthy Volunteers
Official title: A Randomized, Partial Double-Blind, Placebo- and Positive- Controlled, Multiple-Dose, 4-Way Crossover, Thorough QT/QTc (TQT) Study to Investigate the Effect of Relacorilant on Cardiac Repolarization in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This dedicated T/QT study will investigate the effect of relacorilant on cardiac repolarization in healthy participants.

Detailed description: This four-period crossover study with 12 treatment sequences includes relacorilant administered at therapeutic (400 mg once daily \[QD\]) and supra-therapeutic (800 mg QD) doses, placebo for relacorilant as a negative control, and oral moxifloxacin as a positive control. The positive control will serve to determine the sensitivity of the assay to detect small increases from baseline in the QTc interval. Each of the four treatment periods will last 5 days with a washout of at least 10 days between periods. Relacorilant and placebo to relacorilant will be administered double-blind; moxifloxacin will be administered open label.

Eligibility criteria: Inclusion Criteria:

* Participant with a BMI ≥18.0 kg/m\^2 and ≤30.0 kg/m\^2 at screening
* No clinically significant abnormal findings with the physical examination, medical/surgical/medication history, vital signs, or clinical laboratory assessments and adequate cardiac conduction by electrocardiogram (ECG) without evidence of first-, second- or third-degree atrioventricular block
* Female participants of childbearing potential with a negative serum pregnancy test at screening and urine pregnancy test on Day -1 of Period 1
* All male participants agree to use condom to prevent exposure to partner; male participants with female partner of childbearing potential to use a second method of contraception
* Female participants of childbearing potential agree to use the highly effective contraception of low user dependency
* Participant is willing and able to comply with all study procedures and restrictions
* Participant understands the study procedures and agrees to participate by providing written informed consent.

Exclusion Criteria:

* Participant with history or presence of any clinically significant cardiovascular, pulmonary, respiratory, hepatic, renal, hematological, endocrine, immunologic, dermatologic, neurological, psychiatric disease or disorder or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the participant, interfere with study assessments, or impact the validity of the study results
* Participant with a history or family history of additional risk factors for Torsade de Pointe (TdP)
* Participant with a marked prolongation of ECG intervals, including QTcF \>450 milliseconds (msec), PR \>200 msec, or QRS \>120 msec
* Participant with resting heart rate of \<45beats per minute (bpm) or \>100 bpm
* Participant with clinically significant abnormal ECG results
* Participant who uses medications that could prolong the QT/QTc interval
* Participant taking medications/dietary supplements that are highly dependent on cytochrome (CYP)3A for clearance and cannot undergo dose modification upon co-administration with strong CYP3A inhibitors
* Participant using any strong CYP3A inhibitor/inducer or any other medications prohibited per protocol
* Participant who is receiving testosterone within 40 days prior to study start
* Participant with a positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, or hepatitis C antibody
* Participant with a positive test result for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA test, either asymptomatic or present with symptoms of Coronavirus disease 2019 (COVID-19)
* Participant who has travelled abroad within 3 months prior to the screening visit or plans to travel abroad during the study
* Participant who has had a major surgery within the last 28 days prior to Screening
* Participant who received any investigational product within 30 days prior to Screening
* Participant who has a known or suspected allergy, or sensitivity to study products, or any of its ingredient(s), or to moxifloxacin
* Intolerance to repeated venipuncture or inability to swallow capsules
* Donation of blood within 56 days or plasma within 14 days prior to Screening or plans to donate during the entire study period
* Positive alcohol test and/or positive drugs of abuse screen or reports of a history of substance or alcohol abuse within 1 year prior to Screening
* Female participant who is pregnant, breastfeeding, or is planning to become pregnant during the entire study period
* Male participant with pregnant partner.

Primary outcomes:
measure: Placebo-corrected Change from Baseline in Cardiac QT Interval Corrected by Fridericia's Formula (QTcF)
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Secondary outcomes:
measure: Change from Baseline in Cardiac QTcF
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
measure: Change from Baseline in Heart Rate (HR)
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
measure: Placebo-corrected Change from Baseline in HR
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
measure: Change from Baseline in Cardiac PR Interval
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
measure: Placebo-corrected Change from Baseline in Cardiac PR Interval
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
measure: Change from Baseline in Cardiac QRS Intervals
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
measure: Placebo-corrected Change from Baseline in Cardiac QRS Intervals
timeFrame: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
measure: Number of Participants with a Categorical Outlier in QTcF
timeFrame: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
measure: Number of Participants with a Categorical Outlier in HR
timeFrame: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
measure: Number of Participants with a Categorical Outlier in PR Interval
timeFrame: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
measure: Number of Participants with a Categorical Outlier in QRS Intervals
timeFrame: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
measure: Number of Participants with a Treatment-emergent Change of T-wave Morphology
timeFrame: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
measure: Number of Participants with a Treatment-emergent Presence of U-waves
timeFrame: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
measure: Maximum Plasma Concentration (Cmax) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
timeFrame: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
measure: Time to Reach Cmax (Tmax) of Plasma Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
timeFrame: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
measure: Minimum Plasma Concentration (Cmin) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
timeFrame: Before dosing on Day 5 of each treatment period
measure: Area Under the Plasma-concentration Curve from Time Zero to Time of Last Measurable Concentration (AUClast) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
timeFrame: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
measure: Area Under the Plasma-concentration Curve from Time Zero to 24 Hours Postdose (AUC0-24) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
timeFrame: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
measure: Number of Participants with One or More Adverse Events
timeFrame: Up to Day 6 in each treatment period (up to 51 days)
measure: Number of Participants Discontinued From Study Treatment due to an Adverse Event
timeFrame: Up to Day 6 of each treatment period (up to 51 days)
Other outcomes:
Locations:
city: Springfield
country: United States
facility: Single Site
state: Missouri
Study officials:
affiliation: Corcept Therapeutics
name: Joseph Custodio, PhD
role: STUDY_DIRECTOR
References: