HealthyPhase 1NCT03335956
CORT125281 Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
A Phase 1 study testing CORT125281, 40mg, fasted, Prednisone 25mg, fasted and Pioglitazone 15mg Tablet in people with Healthy, run by Corcept Therapeutics at 1 site in United Kingdom.
Trial summary
This initial Phase I study will evaluate the dose-related safety and tolerability pharmacokinetics (PK) of CORT125281, and CORT125324 (active metabolite), and pharmacodynamics (PD) after single and multiple ascending oral doses of CORT125281 in healthy subjects. 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?
- CORT125281, 40mg, fasted, Prednisone 25mg, fasted and Pioglitazone 15mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Sep 2017to 25 Jun 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
- Give written informed consent
- If male, have undergone vasectomy, with no wish to have the procedure reversed
- If female, using appropriate precautions to avoid pregnancy, defined as of nonchildbearing potential (ie, postmenopausal or permanently sterilised) or using highly effective contraception with low user-dependency
- A woman is postmenopausal if it is more than 12 months since her last menstruation, without an alternative medical cause. A concentration of FSH in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy.
- Accepted methods of permanent sterilization methods are hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
- An IUD is the only acceptable method of highly effective contraception with low user-dependency, provided that the subject has tolerated its use for at least 3 months before the first dose of study medication and undertakes not to have it removed for 1 month after the last dose.
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- Be aged 18 to 65 years inclusive
- Have a BMI of 19 to 30 kg/m2, inclusive
- Be willing to comply with study restrictions as described in Section 4.6
- Be able to comply with the requirements of the entire study
- Be judged to be in good health, based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory findings
- For multiple dose cohorts, have a morning serum cortisol within the local reference range at screening and/or Day -1
- Have suitable veins for multiple venepunctures/cannulation
- Be able to swallow size 0 capsules whole
Who cannot join
- Be an employee or immediate family member of the CRU or Corcept
- Have been previously enrolled in this study
- Have multiple drug allergies, or be allergic to any of the components of study medication, its matching placebo, challenge agents or probe substrates (see Section 5.1)
- Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition) or activation (eg, immunodeficiency, active infection) Subjects with inactive seasonal hay fever may be included. Subjects with childhood (aged less than 18 years) asthma may be included provided they have had no symptoms and required no treatment for at least 5 years
- In the 6 calendar months before study drug administration, on average
- Have smoked more than 5 cigarettes/day
Show all 24Show fewer
- Have consumed more than 14 units (female) or 21 units (male) of alcohol/week
- Consumed liquorice or other glycyrrhetic acid derivatives regularly, in the judgement of the Investigator
- In the 3 calendar months before study drug administration
- Have donated blood or plasma in excess of 400 mL
- Have participated in another clinical trial of a new chemical entity or a prescription medicine
- Have a positive test for alcohol, smoking or drugs of abuse at screening or admission to any of the dosing sessions
- Have clinically-relevant abnormal findings on vital signs, physical examination, laboratory screening tests, or 12-lead ECG, at screen and/or before first dose, including but not limited to:
- Abnormal ECG waveform morphology that would preclude accurate measurement of the QT interval
- 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 >20%
- Glomerular filtration rate, estimated using the chronic kidney disease epidemiology (collaboration) (CKD-EPI) method (eGFR; see Section 6.2.5) <60 mL/minute/1.73 m2
- Hypokalaemia (potassium below lower limit of normal)
- ALT, AST and/or gammaglutamyl transferase (GGT) >1.5 times the upper limit of normal
- Seropositive for hepatitis B, hepatitis C or human immunodeficiency viruses.
- Have any medical or social reasons for not participating in the study raised by their General Practitioner/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, as described in Section 4.6.3
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-blind, Randomised, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of SAD and MAD of CORT125281 in Healthy Subjects
This initial Phase I study will evaluate the dose-related safety and tolerability pharmacokinetics (PK) of CORT125281, and CORT125324 (active metabolite), and pharmacodynamics (PD) after single and multiple ascending oral doses of CORT125281 in healthy subjects.
Read the detailed description
Separate single-and multiple-ascending dose (SAD and MAD) parts will be conducted. Throughout each part of the study, safety, pharmacological (PD) and PK effects will be assessed. Safety and tolerability will be assessed using adverse event (AE) monitoring, measurement of vital signs, recording 12-lead electrocardiogram (ECG), physical examination and clinical laboratory safety tests. Blood samples will be collected at intervals for assay of plasma concentration of CORT125281 and CORT125324.
The SAD part of the study is double-blind, randomized and placebo-controlled with respect to CORT125281. Two cohorts, each of 9 subjects, will receive three sequential single doses of the investigational medicinal product (IMP), either CORT125281 at the assigned dose level or placebo, in a partial within-subject crossover manner. The starting dose is CORT125281, 40 mg; the rules for determining later doses are detailed within the protocol. The PD effects of CORT125281 will be examined by testing its ability to ameliorate the pharmacological effects of a concomitantly administered dose of prednisone.
The MAD part of the study will be double-blind, randomized, placebo-controlled and parallel-group with respect to CORT125281. Up to four cohorts of 8 subjects, randomized so that 6 receive CORT125281 and 2 receive placebo, will participate in the study, so that up to four dose levels of CORT125281 are studied in total. An exploratory assessment will be made of the effect of repeated doses of CORT125281 on exposure to pioglitazone, probe substrate for CYP2C8. Each subject will be admitted on Day-1 for baseline assessments. On Day1, subjects will receive a single oral dose of pioglitazone, 15mg. From Day3 to Day16 (14 days), subjects will be dosed daily with IMP (CORT125281 at the selected dose or placebo). On Day13, subjects will receive a second dose of pioglitazone, 15 mg.
- Conditions
- Healthy
- Being tested
- CORT125281, 40mg, fasted, Prednisone 25mg, fasted, Placebo oral capsule, fasted, Pioglitazone 15mg Tablet, Placebo oral capsule, fed
- Keywords
- Glucocorticoid receptor; antagonist
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CORT125281, 40mg, fastedDrug
CORT125281 is supplied as capsules for oral dosing
Prednisone 25mg, fastedDrug
Challenge Agent, Dose and Route of Administration:
Standard release 25 mg tablets, orally administered
Placebo oral capsule, fastedDrug
Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered
Pioglitazone 15mg TabletDrug
Probe Substrate, Dose and Route of Administration:
15 Mg tablet, orally administered
Placebo oral capsule, fedDrug
Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered
Prednisone 25mg, fedDrug
Challenge Agent, Dose and Route of Administration:
Standard release 25 mg tablets, orally administered
CORT125281, 120mg, fastedDrug
CORT125281 is supplied as capsules for oral dosing
CORT125281, 360mg, fastedDrug
CORT125281 is supplied as capsules for oral dosing
CORT125281, 720mg, fastedDrug
CORT125281 is supplied as capsules for oral dosing
CORT125281, 360mg, fedDrug
CORT125281 is supplied as capsules for oral dosing
CORT125281, 360mgDrug
CORT125281 is supplied as capsules for oral dosing twice, 12 hours apart, fasted (morning) and after evening meal
CORT125281, 120mgDrug
CORT125281 is supplied as capsules for oral dosing once daily
CORT125281, 180mgDrug
CORT125281 is supplied as capsules for oral dosing twice daily
CORT125281, 240mgDrug
CORT125281 is supplied as capsules for oral dosing twice daily
CORT125281, 360mgDrug
CORT125281 is supplied as capsules for oral dosing once daily
Placebo oral capsuleDrug
Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered twice, 12 hours apart, fasted (morning) and after evening meal
Placebo oral capsuleDrug
Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered, twice daily
Placebo oral capsuleDrug
Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered, once daily
| Study group | Role | What they receive |
|---|---|---|
| SAD Part 1 Placebo Cohort 1 Period 1 | Placebo comparator | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: Placebo oral capsule, fasted |
| SAD Part 1 Active Cohort Period 1 | Experimental | Not described Receives: Drug: CORT125281, 40mg, fasted; Drug: Prednisone 25mg, fasted |
| SAD Part 1 Placebo Cohort 1 Period 2 | Placebo comparator | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: Placebo oral capsule, fasted |
| SAD Part 1 Active Cohort 1 Period 2 | Experimental | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: CORT125281, 120mg, fasted |
| SAD Part 1 Placebo Cohort 1 Period 3 | Placebo comparator | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: Placebo oral capsule, fasted |
| SAD Part 1 Active Cohort 1 Period 3 | Experimental | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: CORT125281, 360mg, fasted |
| SAD Part 2 Placebo Cohort 2 Period 4 | Placebo comparator | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: Placebo oral capsule, fasted |
| SAD Part 2 Active Cohort 2 Period 4 | Experimental | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: CORT125281, 720mg, fasted |
| SAD Part 2 Placebo Cohort 2 Period 5 | Placebo comparator | Not described Receives: Drug: Placebo oral capsule, fed; Drug: Prednisone 25mg, fed |
| SAD Part 2 Active Cohort 2 Period 5 | Experimental | Not described Receives: Drug: Prednisone 25mg, fed; Drug: CORT125281, 360mg, fed |
| SAD Part 2 Placebo Cohort 2 Period 6 | Placebo comparator | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: Placebo oral capsule |
| SAD Part 2 Active Cohort 2 Period 6 | Experimental | Not described Receives: Drug: Prednisone 25mg, fasted; Drug: CORT125281, 360mg |
| MAD Placebo Cohort 1 | Placebo comparator | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: Placebo oral capsule |
| MAD Active Cohort 1 | Experimental | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: CORT125281, 120mg |
| MAD Placebo Cohort 2 | Placebo comparator | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: Placebo oral capsule |
| MAD Active Cohort 2 | Experimental | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: CORT125281, 180mg |
| MAD Placebo Cohort 3 | Placebo comparator | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: Placebo oral capsule |
| MAD Active Cohort 3 | Experimental | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: CORT125281, 240mg |
| MAD Placebo Cohort 4 | Placebo comparator | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: Placebo oral capsule |
| MAD Active Cohort 4 | Experimental | Not described Receives: Drug: Pioglitazone 15mg Tablet; Drug: CORT125281, 360mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AEs)
Measured: SAD Cohorts Day 1 to Day 14; MAD Cohorts Day 1 to Day 30
Secondary outcomes (27)
AUCtau Pharmacokinetic (PK) parameter
Area under the curve over a dose-interval (AUCtau)
Measured: MAD Cohorts Day 3 to 19
AUC 0-tz PK parameter
Area under the curve from the time of dosing until the last quantifiable concentration (AUC 0-tz)
Measured: CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15
AUC 0-infinity PK parameter
Area under the curve from the time of dosing extrapolated to infinity (AUC 0-infinity)
Measured: CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15
Cmax PK parameter
Maximum concentration (Cmax)
Measured: CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15
Cmin PK parameter
Minimum concentration within a dose interval (Cmin)
Measured: MAD Cohorts Day 3 to 19
Tmax PK parameter
Time to maximum concentration (Tmax)
Measured: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
tlag PK parameter
Latest time after dosing before the first quantifiable concentration (tlag)
Measured: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
apparent terminal rate constant PK parameter
Measured: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
t1/2 PK parameter
Apparent terminal elimination half-life (t1/2)
Measured: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
MRT PK parameter
Mean residence time (MRT)
Measured: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
Vz/F PK parameter
Apparent oral volume of distribution during the terminal elimination phase (Vz/F)
Measured: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
CL/F PK parameter
Apparent oral clearance (CL/F)
Measured: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
Observed accumulation ratio PK parameter
Measured: MAD Cohorts Day 3 to 19
4β-OH cholesterol PK parameter
4β-Hydroxycholesterol (4β-OH)
Measured: MAD Cohorts Day 1 to Day 17
Pharmacodynamics (PD) Peripheral blood neutrophil, eosinophil and lymphocyte counts
Measured: SAD Cohorts pre-dose through 24 hours post dose
PD Serum osteocalcin
Measured: SAD Cohorts pre-dose through 24 hours post dose
PD Pre- and postprandial blood glucose
Measured: SAD Cohorts Day 1, pre-dose to 6 hours post dose
PD Cytokines
Measured: SAD Cohorts Day 1, pre-dose to 24 hours post dose; MAD Cohorts Day 3 to Day 10
PD T cell profiling by flow cytometry
Measured: SAD Cohorts Day 1, pre-dose to 24 hours post dose; MAD Cohorts Day 3 to Day 10
PD Gene expression for glucocorticoid-modulated genes
Measured: SAD Cohorts Day 1, pre-dose to 4 hours post dose
PD Cortisol
Measured: MAD Cohorts pre-dose to Day 16
PD ACTH
Adrenocorticotropic hormone (ACTH)
Measured: MAD Cohorts pre-dose to Day 16
PD DHEA S
Dehydroepiandrosterone sulphate (DHEA-S)
Measured: MAD Cohorts Day 3 to Day 16
PD androstenedione
Measured: MAD Cohorts Day 3 to Day 16
PD Fasting glucose
Measured: MAD Cohorts Day 1 to Day 13
PD insulin
Measured: MAD Cohorts Day 1 to Day 13
PD HOMA-IR
Homeostatic model assessment of insulin-resistance (HOMA-IR)
Measured: MAD Cohorts Day 1 to Day 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study start21 Sep 2017
- Primary completion31 May 2018
- Study completion25 Jun 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corcept Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stacie Shepherd, M.D., Ph.D., Study director, Corcept Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03335956
- Sponsor's protocol ID
- CORT125281-600
- Status last verified
- Jul 2018
- First submitted
- 31 Oct 2017
- Last updated
- 26 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomised, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of SAD and MAD of CORT125281 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03335956
- Acronym / sponsor ID
- CORT125281-600
- Conditions
- Healthy
- Keywords
- Glucocorticoid receptor; antagonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Corcept TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 21 Sep 2017 (actual)
- Primary completion
- 31 May 2018 (actual)
- Study completion
- 25 Jun 2018 (actual)
- First posted
- 8 Nov 2017 (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 initial Phase I study will evaluate the dose-related safety and tolerability pharmacokinetics (PK) of CORT125281, and CORT125324 (active metabolite), and pharmacodynamics (PD) after single and multiple ascending oral doses of CORT125281 in healthy subjects.
Detailed description
Separate single-and multiple-ascending dose (SAD and MAD) parts will be conducted. Throughout each part of the study, safety, pharmacological (PD) and PK effects will be assessed. Safety and tolerability will be assessed using adverse event (AE) monitoring, measurement of vital signs, recording 12-lead electrocardiogram (ECG), physical examination and clinical laboratory safety tests. Blood samples will be collected at intervals for assay of plasma concentration of CORT125281 and CORT125324.
The SAD part of the study is double-blind, randomized and placebo-controlled with respect to CORT125281. Two cohorts, each of 9 subjects, will receive three sequential single doses of the investigational medicinal product (IMP), either CORT125281 at the assigned dose level or placebo, in a partial within-subject crossover manner. The starting dose is CORT125281, 40 mg; the rules for determining later doses are detailed within the protocol. The PD effects of CORT125281 will be examined by testing its ability to ameliorate the pharmacological effects of a concomitantly administered dose of prednisone.
The MAD part of the study will be double-blind, randomized, placebo-controlled and parallel-group with respect to CORT125281. Up to four cohorts of 8 subjects, randomized so that 6 receive CORT125281 and 2 receive placebo, will participate in the study, so that up to four dose levels of CORT125281 are studied in total. An exploratory assessment will be made of the effect of repeated doses of CORT125281 on exposure to pioglitazone, probe substrate for CYP2C8. Each subject will be admitted on Day-1 for baseline assessments. On Day1, subjects will receive a single oral dose of pioglitazone, 15mg. From Day3 to Day16 (14 days), subjects will be dosed daily with IMP (CORT125281 at the selected dose or placebo). On Day13, subjects will receive a second dose of pioglitazone, 15 mg.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 20
| Arm | Type | Receives |
|---|---|---|
| SAD Part 1 Placebo Cohort 1 Period 1 | Placebo comparator | Drug: Prednisone 25mg, fasted, Drug: Placebo oral capsule, fasted |
| SAD Part 1 Active Cohort Period 1 | Experimental | Drug: CORT125281, 40mg, fasted, Drug: Prednisone 25mg, fasted |
| SAD Part 1 Placebo Cohort 1 Period 2 | Placebo comparator | Drug: Prednisone 25mg, fasted, Drug: Placebo oral capsule, fasted |
| SAD Part 1 Active Cohort 1 Period 2 | Experimental | Drug: Prednisone 25mg, fasted, Drug: CORT125281, 120mg, fasted |
| SAD Part 1 Placebo Cohort 1 Period 3 | Placebo comparator | Drug: Prednisone 25mg, fasted, Drug: Placebo oral capsule, fasted |
| SAD Part 1 Active Cohort 1 Period 3 | Experimental | Drug: Prednisone 25mg, fasted, Drug: CORT125281, 360mg, fasted |
| SAD Part 2 Placebo Cohort 2 Period 4 | Placebo comparator | Drug: Prednisone 25mg, fasted, Drug: Placebo oral capsule, fasted |
| SAD Part 2 Active Cohort 2 Period 4 | Experimental | Drug: Prednisone 25mg, fasted, Drug: CORT125281, 720mg, fasted |
| SAD Part 2 Placebo Cohort 2 Period 5 | Placebo comparator | Drug: Placebo oral capsule, fed, Drug: Prednisone 25mg, fed |
| SAD Part 2 Active Cohort 2 Period 5 | Experimental | Drug: Prednisone 25mg, fed, Drug: CORT125281, 360mg, fed |
| SAD Part 2 Placebo Cohort 2 Period 6 | Placebo comparator | Drug: Prednisone 25mg, fasted, Drug: Placebo oral capsule |
| SAD Part 2 Active Cohort 2 Period 6 | Experimental | Drug: Prednisone 25mg, fasted, Drug: CORT125281, 360mg |
| MAD Placebo Cohort 1 | Placebo comparator | Drug: Pioglitazone 15mg Tablet, Drug: Placebo oral capsule |
| MAD Active Cohort 1 | Experimental | Drug: Pioglitazone 15mg Tablet, Drug: CORT125281, 120mg |
| MAD Placebo Cohort 2 | Placebo comparator | Drug: Pioglitazone 15mg Tablet, Drug: Placebo oral capsule |
| MAD Active Cohort 2 | Experimental | Drug: Pioglitazone 15mg Tablet, Drug: CORT125281, 180mg |
| MAD Placebo Cohort 3 | Placebo comparator | Drug: Pioglitazone 15mg Tablet, Drug: Placebo oral capsule |
| MAD Active Cohort 3 | Experimental | Drug: Pioglitazone 15mg Tablet, Drug: CORT125281, 240mg |
| MAD Placebo Cohort 4 | Placebo comparator | Drug: Pioglitazone 15mg Tablet, Drug: Placebo oral capsule |
| MAD Active Cohort 4 | Experimental | Drug: Pioglitazone 15mg Tablet, Drug: CORT125281, 360mg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Give written informed consent
- If male, have undergone vasectomy, with no wish to have the procedure reversed
- If female, using appropriate precautions to avoid pregnancy, defined as of nonchildbearing potential (ie, postmenopausal or permanently sterilised) or using highly effective contraception with low user-dependency
- Be aged 18 to 65 years inclusive
- Have a BMI of 19 to 30 kg/m2, inclusive
Key exclusion criteria (24 listed)
- Be an employee or immediate family member of the CRU or Corcept
- Have been previously enrolled in this study
- Have multiple drug allergies, or be allergic to any of the components of study medication, its matching placebo, challenge agents or probe substrates (see Section 5.1)
- Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition) or activation (eg, immunodeficiency, active infection) Subjects with inactive seasonal hay fever may be included. Subjects with childhood (aged less than 18 years) asthma may be included provided they have had no symptoms and required no treatment for at least 5 years
- In the 6 calendar months before study drug administration, on average
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 |
|---|---|---|
| CORT125281, 40mg, fastedCORT125281 is supplied as capsules for oral dosing | Drug | SAD Part 1 Active Cohort Period 1 |
| Prednisone 25mg, fastedChallenge Agent, Dose and Route of Administration: Standard release 25 mg tablets, orally administered | Drug | SAD Part 1 Active Cohort 1 Period 2, SAD Part 1 Active Cohort 1 Period 3, SAD Part 1 Active Cohort Period 1, SAD Part 1 Placebo Cohort 1 Period 1, SAD Part 1 Placebo Cohort 1 Period 2, SAD Part 1 Placebo Cohort 1 Period 3, SAD Part 2 Active Cohort 2 Period 4, SAD Part 2 Active Cohort 2 Period 6, SAD Part 2 Placebo Cohort 2 Period 4, SAD Part 2 Placebo Cohort 2 Period 6 |
| Placebo oral capsule, fastedReference Therapy, Dose and Route of Administration: Placebo capsule, orally administered | Drug | SAD Part 1 Placebo Cohort 1 Period 1, SAD Part 1 Placebo Cohort 1 Period 2, SAD Part 1 Placebo Cohort 1 Period 3, SAD Part 2 Placebo Cohort 2 Period 4 |
| Pioglitazone 15mg TabletProbe Substrate, Dose and Route of Administration: 15 Mg tablet, orally administered | Drug | MAD Active Cohort 1, MAD Active Cohort 2, MAD Active Cohort 3, MAD Active Cohort 4, MAD Placebo Cohort 1, MAD Placebo Cohort 2, MAD Placebo Cohort 3, MAD Placebo Cohort 4 |
| Placebo oral capsule, fedReference Therapy, Dose and Route of Administration: Placebo capsule, orally administered | Drug | SAD Part 2 Placebo Cohort 2 Period 5 |
| Prednisone 25mg, fedChallenge Agent, Dose and Route of Administration: Standard release 25 mg tablets, orally administered | Drug | SAD Part 2 Active Cohort 2 Period 5, SAD Part 2 Placebo Cohort 2 Period 5 |
| CORT125281, 120mg, fastedCORT125281 is supplied as capsules for oral dosing | Drug | SAD Part 1 Active Cohort 1 Period 2 |
| CORT125281, 360mg, fastedCORT125281 is supplied as capsules for oral dosing | Drug | SAD Part 1 Active Cohort 1 Period 3 |
| CORT125281, 720mg, fastedCORT125281 is supplied as capsules for oral dosing | Drug | SAD Part 2 Active Cohort 2 Period 4 |
| CORT125281, 360mg, fedCORT125281 is supplied as capsules for oral dosing | Drug | SAD Part 2 Active Cohort 2 Period 5 |
| CORT125281, 360mgCORT125281 is supplied as capsules for oral dosing twice, 12 hours apart, fasted (morning) and after evening meal | Drug | SAD Part 2 Active Cohort 2 Period 6 |
| CORT125281, 120mgCORT125281 is supplied as capsules for oral dosing once daily | Drug | MAD Active Cohort 1 |
| CORT125281, 180mgCORT125281 is supplied as capsules for oral dosing twice daily | Drug | MAD Active Cohort 2 |
| CORT125281, 240mgCORT125281 is supplied as capsules for oral dosing twice daily | Drug | MAD Active Cohort 3 |
| CORT125281, 360mgCORT125281 is supplied as capsules for oral dosing once daily | Drug | MAD Active Cohort 4 |
| Placebo oral capsuleReference Therapy, Dose and Route of Administration: Placebo capsule, orally administered twice, 12 hours apart, fasted (morning) and after evening meal | Drug | SAD Part 2 Placebo Cohort 2 Period 6 |
| Placebo oral capsuleReference Therapy, Dose and Route of Administration: Placebo capsule, orally administered, twice daily | Drug | MAD Placebo Cohort 2, MAD Placebo Cohort 3 |
| Placebo oral capsuleReference Therapy, Dose and Route of Administration: Placebo capsule, orally administered, once daily | Drug | MAD Placebo Cohort 1, MAD Placebo Cohort 4 |
Primary outcome
Adverse Events (AEs)
Time frame: SAD Cohorts Day 1 to Day 14; MAD Cohorts Day 1 to Day 30
27 secondary outcomes
AUCtau Pharmacokinetic (PK) parameter
Time frame: MAD Cohorts Day 3 to 19
AUC 0-tz PK parameter
Time frame: CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15
AUC 0-infinity PK parameter
Time frame: CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15
Cmax PK parameter
Time frame: CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15
Cmin PK parameter
Time frame: MAD Cohorts Day 3 to 19
Tmax PK parameter
Time frame: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
tlag PK parameter
Time frame: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
apparent terminal rate constant PK parameter
Time frame: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
t1/2 PK parameter
Time frame: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
MRT PK parameter
Time frame: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
Vz/F PK parameter
Time frame: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
CL/F PK parameter
Time frame: SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19
Observed accumulation ratio PK parameter
Time frame: MAD Cohorts Day 3 to 19
4β-OH cholesterol PK parameter
Time frame: MAD Cohorts Day 1 to Day 17
Pharmacodynamics (PD) Peripheral blood neutrophil, eosinophil and lymphocyte counts
Time frame: SAD Cohorts pre-dose through 24 hours post dose
PD Serum osteocalcin
Time frame: SAD Cohorts pre-dose through 24 hours post dose
PD Pre- and postprandial blood glucose
Time frame: SAD Cohorts Day 1, pre-dose to 6 hours post dose
PD Cytokines
Time frame: SAD Cohorts Day 1, pre-dose to 24 hours post dose; MAD Cohorts Day 3 to Day 10
PD T cell profiling by flow cytometry
Time frame: SAD Cohorts Day 1, pre-dose to 24 hours post dose; MAD Cohorts Day 3 to Day 10
PD Gene expression for glucocorticoid-modulated genes
Time frame: SAD Cohorts Day 1, pre-dose to 4 hours post dose
PD Cortisol
Time frame: MAD Cohorts pre-dose to Day 16
PD ACTH
Time frame: MAD Cohorts pre-dose to Day 16
PD DHEA S
Time frame: MAD Cohorts Day 3 to Day 16
PD androstenedione
Time frame: MAD Cohorts Day 3 to Day 16
PD Fasting glucose
Time frame: MAD Cohorts Day 1 to Day 13
PD insulin
Time frame: MAD Cohorts Day 1 to Day 13
PD HOMA-IR
Time frame: MAD Cohorts Day 1 to Day 13
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 26 Jul 2018.
- Individual participant dataSharing planned: Undecided
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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.
Stacie Shepherd, M.D., Ph.D. 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 CORT125281, 40mg, fasted, Prednisone 25mg, fasted and Pioglitazone 15mg Tablet in people with Healthy, run by Corcept Therapeutics at 1 site in United Kingdom.
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 14 inclusion and 24 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 26 Jul 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 Kingdom. 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. Some participants in this study may receive a placebo. 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?
Adverse Events (AEs) (time frame: SAD Cohorts Day 1 to Day 14; MAD Cohorts Day 1 to Day 30). 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 26 Jul 2018.