HealthyPhase 1NCT03457597
Study in Healthy Subjects to Determine the Effect of Relacorilant on Exposure to Probe Substrates for Cytochrome P450s
A Phase 1 study testing Midazolam hydrochloride, Metoprolol tartrate and Pioglitazone hydrochloride in people with Healthy, run by Corcept Therapeutics at 1 site in United States.
Trial summary
This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments: Day 1, single doses of midazolam and metoprolol; Day 2, single doses of pioglitazone, tolbutamide, and… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Midazolam hydrochloride, Metoprolol tartrate and Pioglitazone hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 2018to 28 Apr 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- Give written informed consent.
- 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.
- Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a body weight more than 50 kg (110 pounds).
- 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.
- Be willing to comply with study restrictions
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- Have suitable veins for multiple venipuncture/cannulation.
- 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.
Who cannot join
- Be an employee or immediate family member of the Clinical Research Unit or Corcept.
- Have been previously enrolled in any study of relacorilant.
- Have multiple drug allergies, or be allergic to any of the components of relacorilant.
- Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition).
- Have a history of gastric bypass surgery.
- Have a history of malabsorption syndrome or previous gastrointestinal surgery, with the exception of appendectomy and cholecystectomy, which could affect drug absorption or metabolism.
Show all 22Show fewer
- Current alcohol or substance abuse.
- In the 2 calendar months before first study drug administration, have donated/lost blood or plasma in excess of 400 mL.
- In the 30 days before first study drug administration, have participated in another clinical trial of a new chemical entity or a prescription medicine.
- Have a positive test for alcohol or drugs of abuse at screening or first admission.
- Have a positive test for exogenous glucocorticoids at screening.
- 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**:
- 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)
- 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)
- 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%
- Glomerular filtration rate, estimated using the chronic kidney disease epidemiology (collaboration) (CKD-EPI) method (eGFR; Levey 2009) <60 mL/minute/1.73 m2
- Hypokalemia (potassium below lower limit of normal)
- Alanine aminotransferase (ALT), aspartate amino transferase (AST), and/or gamma- glutamyltransferase (GGT) >1.5 times the upper limit of normal (ULN)
- 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.
- Have any medical or social reasons for not participating in the study raised by their primary care physician.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Subjects to Determine the Effect of Relacorilant on Exposure to Probe Substrates for Cytochrome P450s 3A4, 2C8, 2C9, 2C19, and 2D6
This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments: Day 1, single doses of midazolam and metoprolol; Day 2, single doses of pioglitazone, tolbutamide, and omeprazole; Days 5 to 17, daily doses of relacorilant; Day 14, single doses of midazolam and metoprolol (with relacorilant); and, Day 15, single doses of pioglitazone, tolbutamide, and omeprazole (with relacorilant).
Read the detailed description
This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Subjects will be screened for eligibility for the study within 21 days before the first dose of study drug based on entrance criteria specified in Section 4. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments:
- Day 1: single doses of midazolam and metoprolol
- Day 2: single doses of pioglitazone, tolbutamide, and omeprazole
- Days 5 to 17: daily doses of relacorilant
- Day 14: single doses of midazolam and metoprolol (with relacorilant)
- Day 15: single doses of pioglitazone, tolbutamide, and omeprazole (with relacorilant) Blood samples will be collected before dosing and at intervals up to 24 hours after each midazolam dose, up to 48 hours after each metoprolol, tolbutamide, and omeprazole dose, and up to 72 hours after each pioglitazone dose for assay of the respective probe substrates and relevant metabolites. Additional samples will be collected during the relacorilant dosing period for assay of relacorilant and metabolites to confirm exposure and at the beginning (before dosing on Day 5) and near the end (Day 14) of the relacorilant dosing period for assay for 4β-OH cholesterol, a biomarker for CYP induction.
Safety and tolerability will be monitored using AEs, clinical laboratory evaluations, 12-lead ECG recordings, vital sign and pulse oximetry measurements, 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, 72 hours after the last dose of probe substrate and 24 hours after the last dose of relacorilant. Subjects may leave the CRU after safety review on the morning of Day 18. Each subject will have a follow-up (FU) visit 14 ± 2 days after the last dose of study drug.
- Conditions
- Healthy
- Being tested
- Midazolam hydrochloride, Metoprolol tartrate, Pioglitazone hydrochloride, Tolbutamide, Omeprazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Midazolam hydrochlorideDrug
Also called Versed
Midazolam hydrochloride 2.5 mg
Metoprolol tartrateDrug
Also called Lopressor
Metoprolol tartrate 100 mg
Pioglitazone hydrochlorideDrug
Also called Actos
Pioglitazone hydrochloride 15 mg
TolbutamideDrug
Also called Orinase
Tolbutamide 500 mg
OmeprazoleDrug
Also called Prilosec
Omeprazole 20 mg
RelacorilantDrug
Also called CORT125134
Relacorilant 350mg
| Study group | Role | What they receive |
|---|---|---|
| Period 1 | Experimental | Period 1 (Study Days 1 to 4): Midazolam hydrochloride and metoprolol tartrate will be given once on Day 1. Pioglitazone hydrochloride, tolbutamide and omeprazole will be given once on Day 2 Receives: Drug: Midazolam hydrochloride; Drug: Metoprolol tartrate; Drug: Pioglitazone hydrochloride; Drug: Tolbutamide; Drug: Omeprazole |
| Period 2 | Experimental | Period 2 (Study Days 5 to 13): Relacorilant will be given daily from Day 5 to Day 13. Receives: Drug: Relacorilant |
| Period 3 | Experimental | Period 3 (Study Days 14 to 17): Midazolam hydrochloride and metoprolol tartrate will be given once on Day 14. Pioglitazone hydrochloride, tolbutamide and omeprazole will be given once on Day 15. Relacorilant will be given daily from Day 14 to Day 17. Receives: Drug: Midazolam hydrochloride; Drug: Metoprolol tartrate; Drug: Pioglitazone hydrochloride; Drug: Tolbutamide; Drug: Omeprazole; Drug: Relacorilant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
Ratio of population geometric means (GMR) for Reference Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 or 11 days of daily dosing with relacorilant) areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
Measured: predose to 96 hrs postdose
Secondary outcomes (7)
Area under plasma concentration-time curve extrapolated to infinity (AUCinf)
Ratio of population geometric means (GMR) for Reference Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 days of daily dosing with relacorilant) areas under plasma concentration-time curve extrapolated to infinity (AUCinf)
Measured: predose to 96 hrs postdose
Maximum plasma concentration (Cmax)
Ratio of population geometric means (GMR) for Reference Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 days of daily dosing with relacorilant) maximum plasma concentration (Cmax).
Measured: predose to 96 hrs postdose
Adverse Events
Safety and tolerability measure by number of subjects who experience adverse events
Measured: up to 8 weeks
Safety Labs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Measured: up to 8 weeks
ECGs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Measured: up to 8 weeks
Vital Signs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
Measured: up to 8 weeks
Physical Examinations
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical exams
Measured: up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study start6 Mar 2018
- Primary completion15 Apr 2018
- Study completion28 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corcept Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kirsteen Donaldson, FFPM,DM,FRCP, Study director, Corcept Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03457597
- Sponsor's protocol ID
- CORT125134-126
- Status last verified
- Feb 2018
- First submitted
- 1 Mar 2018
- Last updated
- 17 May 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Subjects to Determine the Effect of Relacorilant on Exposure to Probe Substrates for Cytochrome P450s 3A4, 2C8, 2C9, 2C19, and 2D6
- ClinicalTrials.gov ID
- NCT03457597
- Acronym / sponsor ID
- CORT125134-126
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Corcept TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 6 Mar 2018 (actual)
- Primary completion
- 15 Apr 2018 (actual)
- Study completion
- 28 Apr 2018 (actual)
- First posted
- 7 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments: Day 1, single doses of midazolam and metoprolol; Day 2, single doses of pioglitazone, tolbutamide, and omeprazole; Days 5 to 17, daily doses of relacorilant; Day 14, single doses of midazolam and metoprolol (with relacorilant); and, Day 15, single doses of pioglitazone, tolbutamide, and omeprazole (with relacorilant).
Detailed description
This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Subjects will be screened for eligibility for the study within 21 days before the first dose of study drug based on entrance criteria specified in Section 4. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments:
- Day 1: single doses of midazolam and metoprolol
- Day 2: single doses of pioglitazone, tolbutamide, and omeprazole
- Days 5 to 17: daily doses of relacorilant
- Day 14: single doses of midazolam and metoprolol (with relacorilant)
- Day 15: single doses of pioglitazone, tolbutamide, and omeprazole (with relacorilant) Blood samples will be collected before dosing and at intervals up to 24 hours after each midazolam dose, up to 48 hours after each metoprolol, tolbutamide, and omeprazole dose, and up to 72 hours after each pioglitazone dose for assay of the respective probe substrates and relevant metabolites. Additional samples will be collected during the relacorilant dosing period for assay of relacorilant and metabolites to confirm exposure and at the beginning (before dosing on Day 5) and near the end (Day 14) of the relacorilant dosing period for assay for 4β-OH cholesterol, a biomarker for CYP induction.
Safety and tolerability will be monitored using AEs, clinical laboratory evaluations, 12-lead ECG recordings, vital sign and pulse oximetry measurements, 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, 72 hours after the last dose of probe substrate and 24 hours after the last dose of relacorilant. Subjects may leave the CRU after safety review on the morning of Day 18. Each subject will have a follow-up (FU) visit 14 ± 2 days after the last dose of study drug.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Period 1 | Experimental | Drug: Midazolam hydrochloride, Drug: Metoprolol tartrate, Drug: Pioglitazone hydrochloride, Drug: Tolbutamide, Drug: OmeprazolePeriod 1 (Study Days 1 to 4): Midazolam hydrochloride and metoprolol tartrate will be given once on Day 1. Pioglitazone hydrochloride, tolbutamide and omeprazole will be given once on Day 2 |
| Period 2 | Experimental | Drug: RelacorilantPeriod 2 (Study Days 5 to 13): Relacorilant will be given daily from Day 5 to Day 13. |
| Period 3 | Experimental | Drug: Midazolam hydrochloride, Drug: Metoprolol tartrate, Drug: Pioglitazone hydrochloride, Drug: Tolbutamide, Drug: Omeprazole, Drug: RelacorilantPeriod 3 (Study Days 14 to 17): Midazolam hydrochloride and metoprolol tartrate will be given once on Day 14. Pioglitazone hydrochloride, tolbutamide and omeprazole will be given once on Day 15. Relacorilant will be given daily from Day 14 to Day 17. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- Give written informed consent.
- 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.
- Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a body weight more than 50 kg (110 pounds).
- 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.
Key exclusion criteria (22 listed)
- Be an employee or immediate family member of the Clinical Research Unit or Corcept.
- Have been previously enrolled in any study of relacorilant.
- Have multiple drug allergies, or be allergic to any of the components of relacorilant.
- Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition).
- Have a history of gastric bypass surgery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Midazolam hydrochlorideAlso: VersedMidazolam hydrochloride 2.5 mg | Drug | Period 1, Period 3 |
| Metoprolol tartrateAlso: LopressorMetoprolol tartrate 100 mg | Drug | Period 1, Period 3 |
| Pioglitazone hydrochlorideAlso: ActosPioglitazone hydrochloride 15 mg | Drug | Period 1, Period 3 |
| TolbutamideAlso: OrinaseTolbutamide 500 mg | Drug | Period 1, Period 3 |
| OmeprazoleAlso: PrilosecOmeprazole 20 mg | Drug | Period 1, Period 3 |
| RelacorilantAlso: CORT125134Relacorilant 350mg | Drug | Period 2, Period 3 |
Primary outcome
Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
Time frame: predose to 96 hrs postdose
Ratio of population geometric means (GMR) for Reference Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 or 11 days of daily dosing with relacorilant) areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
7 secondary outcomes
Area under plasma concentration-time curve extrapolated to infinity (AUCinf)
Time frame: predose to 96 hrs postdose
Maximum plasma concentration (Cmax)
Time frame: predose to 96 hrs postdose
Adverse Events
Time frame: up to 8 weeks
Safety Labs
Time frame: up to 8 weeks
ECGs
Time frame: up to 8 weeks
Vital Signs
Time frame: up to 8 weeks
Physical Examinations
Time frame: up to 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kirsteen Donaldson, FFPM,DM,FRCP study director
Corcept Therapeutics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Midazolam hydrochloride, Metoprolol tartrate and Pioglitazone hydrochloride in people with Healthy, run by Corcept Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz) (time frame: predose to 96 hrs postdose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2018.