CORT125281 Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)

NCT03335956 | Completed Phase 1

• 1 other identifier: CORT125281-600
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

Glucocorticoid receptor; antagonist

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs)

  SAD Cohorts Day 1 to Day 14; MAD Cohorts Day 1 to Day 30

Secondary Outcomes (27)

• AUCtau Pharmacokinetic (PK) parameter

  MAD Cohorts Day 3 to 19

• AUC 0-tz PK parameter

  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

  CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15

• Cmax PK parameter

  CORT125281/CORT125324 - SAD Cohorts Day 1 to 4; MAD Cohorts Day 3 to 19; Pioglitizone - MAD Cohort Day 1 to 15

• Cmin PK parameter

  MAD Cohorts Day 3 to 19

Study Arms (20)

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

Interventions

CORT125281, 40mg, fasted DRUG

CORT125281 is supplied as capsules for oral dosing

SAD Part 1 Active Cohort Period 1

Prednisone 25mg, fasted DRUG

Challenge Agent, Dose and Route of Administration: Standard release 25 mg tablets, orally administered

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, fasted DRUG

Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered

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 Tablet DRUG

Probe Substrate, Dose and Route of Administration: 15 Mg tablet, orally administered

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, fed DRUG

Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered

SAD Part 2 Placebo Cohort 2 Period 5

Prednisone 25mg, fed DRUG

Challenge Agent, Dose and Route of Administration: Standard release 25 mg tablets, orally administered

SAD Part 2 Active Cohort 2 Period 5; SAD Part 2 Placebo Cohort 2 Period 5

CORT125281, 120mg, fasted DRUG

CORT125281 is supplied as capsules for oral dosing

SAD Part 1 Active Cohort 1 Period 2

CORT125281, 360mg, fasted DRUG

CORT125281 is supplied as capsules for oral dosing

SAD Part 1 Active Cohort 1 Period 3

CORT125281, 720mg, fasted DRUG

CORT125281 is supplied as capsules for oral dosing

SAD Part 2 Active Cohort 2 Period 4

CORT125281, 360mg, fed DRUG

CORT125281 is supplied as capsules for oral dosing

SAD Part 2 Active Cohort 2 Period 5

CORT125281, 360mg DRUG

CORT125281 is supplied as capsules for oral dosing twice, 12 hours apart, fasted (morning) and after evening meal

SAD Part 2 Active Cohort 2 Period 6

CORT125281, 120mg DRUG

CORT125281 is supplied as capsules for oral dosing once daily

MAD Active Cohort 1

CORT125281, 180mg DRUG

CORT125281 is supplied as capsules for oral dosing twice daily

MAD Active Cohort 2

CORT125281, 240mg DRUG

CORT125281 is supplied as capsules for oral dosing twice daily

MAD Active Cohort 3

Placebo oral capsule DRUG

Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered twice, 12 hours apart, fasted (morning) and after evening meal

SAD Part 2 Placebo Cohort 2 Period 6

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Corcept Therapeutics: lead

Study Sites (1)

Hammersmith Medicines Research

London, United Kingdom

Location

MeSH Terms

Interventions

Prednisone; Pioglitazone; Tablets

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Stacie Shepherd, M.D., Ph.D.

  Corcept Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 8, 2017
• Study Start: September 21, 2017
• Primary Completion: May 31, 2018
• Study Completion: June 25, 2018
• Last Updated: July 26, 2018

Record last verified: 2018-07

Locations

GB (1)