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Study in Healthy Subjects to Determine the Effect of an Inhibitor on Exposure to Relacorilant and Its Metabolites

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ClinicalTrials.gov Identifier: NCT03512548
Recruitment Status : Recruiting
First Posted : April 30, 2018
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Corcept Therapeutics

Brief Summary:

This is an open label, single sequence, crossover study. In Part 1, eligible subjects will participate in 3 treatment periods, in which they will receive the following treatments in turn: 1) In Period 1, a single 350 mg dose of relacorilant administered alone, 2) In Period 2, once daily 200 mg doses of itraconazole administered for 3 days; 3) In Period 3, single 350-mg dose of relacorilant administered with a concomitant 200 mg dose of itraconazole and continued once daily 200 mg doses of itraconazole for three additional days.

If Part 2 is conducted, eligible subjects will participate in 3 treatment periods, in which they will receive the following treatments in turn: 1) In Period A, 14 days of oral dosing with "higher dose" relacorilant alone; 2) In Period B, 14 days of oral dosing with "lower dose" relacorilant alone; 3) In Period C, 14 days of oral dosing with "lower dose" relacorilant in combination with itraconazole.


Condition or disease Intervention/treatment Phase
Healthy Drug: Relacorilant 350mg Drug: Itraconazole Drug: Relacorilant "higher dose" Drug: Relacorilant "lower dose" Phase 1

Detailed Description:

This is an open label, single sequence, crossover study. In Part 1, eligible subjects will participate in 3 treatment periods, in which they will receive the following treatments in turn: 1) In Period 1, a single 350 mg dose of relacorilant administered alone, 2) In Period 2, once daily 200 mg doses of itraconazole administered for 3 days; 3) In Period 3, single 350-mg dose of relacorilant administered with a concomitant 200 mg dose of itraconazole and continued once daily 200 mg doses of itraconazole for three additional days.

Part 2 of the study may be conducted if the results from Part 1 indicate that itraconazole has a clinically meaningful effect on exposure to relacorilant and metabolites. If Part 2 is conducted, eligible subjects will participate in 3 treatment periods, in which they will receive the following treatments in turn: 1) In Period A, 14 days of oral dosing with "higher dose" relacorilant alone; 2) In Period B, 14 days of oral dosing with "lower dose" relacorilant alone; 3) In Period C, 14 days of oral dosing with "lower dose" relacorilant in combination with itraconazole.

Blood samples will be collected before dosing and at intervals up to 96 hours after relacorilant dose in Part 1, and up to 24 hours after the last dose of relacorilant in Part 2. Additional samples will be collected during the itraconazole dosing to confirm exposure.

Safety and tolerability will be monitored using AEs, clinical laboratory evaluations, 12-lead ECG recordings, vital signs, and and physical examinations.

Subjects will be admitted to the Clinical Research Unit (CRU) on the morning of Day −1 following an 8-hour fast for baseline assessments and will remain confined until completion of procedures. Each subject will have a follow-up (FU) visit 14 ± 2 days after the last dose of relacorilant.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Subjects to Determine the Effect of an Inhibitor of Cytochrome P450 3A on Exposure to Relacorilant and Its Main Metabolites
Actual Study Start Date : April 10, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 Period 1
Part 1 Period 1: Relacorilant 350mg will be given once on Day 1
Drug: Relacorilant 350mg
Relacorilant 350mg
Other Name: CORT125134

Experimental: Part 1 Period 2
Part 1 Period 2: Itraconazole 200mg will be given for three days
Drug: Itraconazole
Itraconazole 200 mg
Other Name: Sporanox

Experimental: Part 1 Period 3
Part 1 Period 3: Relacorilant 350mg will be given once with concomitant itraconazole and itraconazole will continue for three additional days
Drug: Relacorilant 350mg
Relacorilant 350mg
Other Name: CORT125134

Drug: Itraconazole
Itraconazole 200 mg
Other Name: Sporanox

Experimental: Part 2 Period A
Part 2 Period A: Relacorilant "higher dose" will be given once daily for 14 days
Drug: Relacorilant "higher dose"
Relacorilant "higher dose"
Other Name: CORT125134

Experimental: Part 2 Period B
Part 2 Period B: Relacorilant "lower dose" will be given once daily for 14 days
Drug: Relacorilant "lower dose"
Relacorilant "lower dose"
Other Name: CORT125134

Experimental: Part 2 Period C
Part 2 Period C: Relacorilant "lower dose" will be given once daily for 14 days in combination with itraconazole
Drug: Itraconazole
Itraconazole 200 mg
Other Name: Sporanox

Drug: Relacorilant "lower dose"
Relacorilant "lower dose"
Other Name: CORT125134




Primary Outcome Measures :
  1. Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz) [ Time Frame: predose to 96 hrs postdose in Part 1 and predose to 24 hrs after last dose in Part 2 ]
    Ratio of population geometric means (GMR) for Reference (following oral administration of relacorilant alone) and Test (following the same dose given to subjects concomitantly with itraconazole) areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)


Secondary Outcome Measures :
  1. Area under plasma concentration-time curve extrapolated to infinity (AUCinf) [ Time Frame: predose to 96 hrs postdose in Part 1 and predose to 24 hrs after last dose in Part 2 ]
    Ratio of population geometric means (GMR) for Reference (following oral administration of relacorilant alone) and Test (following the same dose given to subjects concomitantly with itraconazole) areas under plasma concentration-time curve extrapolated to infinity (AUCinf)

  2. Maximum plasma concentration (Cmax) [ Time Frame: predose to 96 hrs postdose in Part 1 and predose to 24 hrs after last dose in Part 2 ]
    Ratio of population geometric means (GMR) for Reference (following oral administration of relacorilant alone) and Test (following the same dose given to subjects concomitantly with itraconazole) maximum plasma concentration (Cmax).

  3. Number and Severity of Treatment Emergent Adverse Events [ Time Frame: up to 7 weeks in Part 1 and up to 14 weeks in Part 2 ]
    Treatment Emergent Adverse Events will be summarized overall and by treatment based on their frequency and severity of treatment emergent adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Able to understand the purpose and risks of the study; willing and able to adhere to scheduled visits, treatment plans, laboratory tests, and other study evaluations and procedures.
  2. Give written informed consent.
  3. Be males or nonpregnant, nonlactating females judged to be in good health, based on the results of medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory findings.
  4. Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a body weight more than 50 kg (110 pounds).
  5. Be a nonsmoker. Use of nicotine or nicotine-containing products must be discontinued at least 90 days prior to the first dose of study drug.
  6. Be willing to comply with study restrictions
  7. Have suitable veins for multiple venipuncture/cannulation.
  8. Female subjects must be either of nonchildbearing potential (ie, postmenopausal or permanently sterilized) or use highly effective contraception with low user-dependency.

    • The only acceptable method of highly effective contraception with low user-dependency is an intrauterine device (IUD). Use of hormonal contraception (by any route, including intrauterine hormone releasing systems) or hormone replacement therapy is NOT acceptable.

Exclusion Criteria:

  1. Be an employee or immediate family member of the Clinical Research Unit or Corcept.
  2. Have been previously enrolled in any study of relacorilant.
  3. Have multiple drug allergies, or be allergic to any of the components of Relacorilant and/or itraconazole.
  4. Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition).
  5. Have a history of malabsorption syndrome or previous gastrointestinal surgery, with the exception of appendectomy and cholecystectomy, which could affect drug absorption or metabolism.
  6. Current alcohol or substance abuse.
  7. In the 2 calendar months before first study drug administration, have donated/lost blood or plasma in excess of 400 mL.
  8. In the 30 days before first study drug administration, have participated in another clinical trial of a new chemical entity or a prescription medicine.
  9. Have a positive test for alcohol or drugs of abuse at screening or first admission.
  10. Have a positive test for exogenous glucocorticoids at screening.
  11. Have clinically relevant abnormal findings on vital signs, physical examination, laboratory screening tests, or 12-lead ECG, at screening and/or before first study drug administration, including but not limited to**:

    1. QT interval corrected for heart rate (QTc) using Fridericia's equation (QTcF) >450 ms (from mean of 3 supine ECGs, performed at least 2 minutes apart)
    2. Stage 2 or higher hypertension (supine/semi-recumbent systolic blood pressure [SBP] >160 mmHg, diastolic blood pressure [DBP] >100 mmHg; based on mean of duplicate values recorded at least 2 minutes apart)
    3. Stage 1 hypertension (supine/semi-recumbent SBP 140-160 mmHg, DBP 90-100 mmHg; based on mean of duplicate values recorded at least 2 minutes apart) associated with indication for treatment ie, evidence of end-organ damage, diabetes, or a 10-year cardiovascular risk, estimated using a standard calculator, (eg, QRISK2-2016) greater than 20%
    4. Glomerular filtration rate, estimated using the chronic kidney disease epidemiology (collaboration) (CKD-EPI) method (eGFR; Levey 2009) <60 mL/minute/1.73 m2
    5. Hypokalemia (potassium below lower limit of normal)
    6. Alanine aminotransferase (ALT), aspartate amino transferase (AST), and/or gamma- glutamyltransferase (GGT) >1.5 times the upper limit of normal (ULN)
    7. Seropositive for hepatitis B, hepatitis C, or human immunodeficiency (HIV) viruses **For purposes of qualifying any given subject for study participation, out-of-range values may be repeated once.
  12. Have any medical or social reasons for not participating in the study raised by their primary care physician.
  13. Have any other condition that might increase the risk to the individual or decrease the chance of obtaining satisfactory data, as assessed by the Investigator.
  14. Taken any prohibited prior medication within protocol designated timeframes, such as or including any glucocorticoid, strong inducers, inhibitors or substrates of CYP enzymes involved in drug-drug-interactions, hormonal contraception or hormone replacement therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03512548


Contacts
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Contact: Clinical Study Lead 650-327-3270 DDIStudies@corcept.com

Locations
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United States, Arizona
Celerion Recruiting
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Corcept Therapeutics
Investigators
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Study Director: Kirsteen Donaldson, FFPM,DM,FRCP Corcept Therapeutics

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Responsible Party: Corcept Therapeutics
ClinicalTrials.gov Identifier: NCT03512548     History of Changes
Other Study ID Numbers: CORT125134-124
First Posted: April 30, 2018    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors