First-in-human Study in Healthy Subjects

NCT03315338 | Completed Phase 1

• 1 other identifier: CORT118335-850
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

This initial Phase I study will evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of CORT118335, the effect of concomitant administration with food on exposure to CORT118335, and its pharmacological effect in healthy subjects.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs)

  SAD Cohorts: Day -28 to Day 7; Part 2A Cohorts: Day -28 to Day 14; Part 2B Cohorts: Day -28 to Day 21; MAD Cohorts: Day -28 to Day 21

Secondary Outcomes (21)

• QT interval corrected for heart rate using Fridericia's formula (QTcF) exposure-response analysis

  SAD parts: Pre dose through 24 hours post dose. MAD parts: Pre first dose through 24 hours post final dose of Investigational Medicinal Product (IMP

• tlag Pharmacokinetic (PK) parameter

  SAD parts: Pre dose through 96 hours post dose; MAD parts: Pre first dose through 96 hours post final dose of IMP

• tmax PK parameter

  SAD parts: Pre dose through 96 hours post dose; MAD parts: Pre first dose through 96 hours post final dose of IMP

• Cmax PK parameter

  SAD parts: Pre dose through 96 hours post dose; MAD parts: Pre first dose through 96 hours post final dose of IMP

• tmin (MAD only) PK parameter

  MAD parts: Pre first dose through 96 hours post final dose of IMP

Study Arms (31)

SAD Part 1 Active Cohort A

EXPERIMENTAL

CORT118335, 25 mg

Drug: CORT118335, 25 mg

SAD Part 1 Placebo oral capsule Cohort A

PLACEBO COMPARATOR

Drug: Placebo oral capsule

SAD Part 1 Active Cohort B

EXPERIMENTAL

CORT118335, 75mg

Drug: CORT118335, 75mg

SAD Part 1 Placebo Cohort B

PLACEBO COMPARATOR

Drug: Placebo oral capsule

SAD Part 1 Active Cohort C

EXPERIMENTAL

CORT118335, 225mg

Drug: CORT118335, 225mg

SAD Part 1 Placebo Cohort C

PLACEBO COMPARATOR

Drug: Placebo oral capsule

SAD Part 1 Active Cohort D

EXPERIMENTAL

CORT118335, 675mg

Drug: CORT118335, 675mg

SAD Part 1 Placebo Cohort D

PLACEBO COMPARATOR

Drug: Placebo oral capsule

SAD Part 2 Active Cohort A, Fasting

EXPERIMENTAL

CORT118335, 600mg, is supplied as capsules for oral dosing given after an overnight fast

Drug: CORT118335, 600mg

SAD Part 2 Active Cohort A, Fed

EXPERIMENTAL

CORT118335, 600mg, is supplied as capsules for oral dosing given after a high-fat breakfast

Drug: CORT118335, 600mg

SAD Part 2 Placebo PD Effect Cohort B

PLACEBO COMPARATOR

Drug: Prednisone Oral Tablet; Drug: Glucose; Drug: Placebo oral capsule

SAD Part 2 Active PD Effect Cohort B: 630mg of CORT118335

EXPERIMENTAL

Drug: Prednisone Oral Tablet; Drug: Glucose; Drug: CORT118335, 630mg

SAD Part 2 Active PD Effect Cohort B: 675mg of CORT118335

EXPERIMENTAL

Drug: Prednisone Oral Tablet; Drug: Glucose; Drug: CORT118335, 675mg

MAD Part 3 Active Cohort A

EXPERIMENTAL

CORT118335, 375mg qd for 14 days

Drug: CORT118335, 375mg

MAD Part 3 Placebo Cohort A

PLACEBO COMPARATOR

Placebo qd for 14 days

Drug: Placebo oral capsule

SAD Part 4 Active Cohort A

EXPERIMENTAL

CORT118335, 100mg

Drug: CORT118335, 100mg

SAD Part 4 Placebo Cohort A

PLACEBO COMPARATOR

Drug: Placebo oral suspension

SAD Part 4 Active Cohort B

EXPERIMENTAL

CORT118335, 300mg

Drug: CORT118335, 300mg

SAD Part 4 Placebo Cohort B

PLACEBO COMPARATOR

Drug: Placebo oral suspension

SAD Part 4 Active Cohort C, Fasting

EXPERIMENTAL

CORT118335, 900mg is supplied as suspension for oral dosing given after an overnight fast

Drug: CORT118335, 900mg

SAD Part 4 Active Cohort C, Fed

EXPERIMENTAL

CORT118335, 900mg is supplied as suspension for oral dosing given after a high-fat breakfast

Drug: CORT118335, 900mg

SAD Part 4 Placebo Cohort C, Fasting

PLACEBO COMPARATOR

Supplied as suspension for oral dosing given after an overnight fast

Drug: Placebo oral suspension

SAD Part 4 Placebo Cohort C, Fed

PLACEBO COMPARATOR

Supplied as suspension for oral dosing given after a high-fat breakfast

Drug: Placebo oral suspension

SAD Part 4 Active Cohort Part D

EXPERIMENTAL

CORT118335, 1500mg

Drug: CORT118335, 1500mg

SAD Part 4 Placebo Cohort D

PLACEBO COMPARATOR

Drug: Placebo oral suspension

MAD Part 5 Active Cohort A

EXPERIMENTAL

CORT118335, 150mg

Drug: CORT118335, 150mg

MAD Part 5 Placebo Cohort A

PLACEBO COMPARATOR

Drug: Placebo oral suspension

MAD Part 5 Active Cohort B

EXPERIMENTAL

CORT118335, dose to be determined

Drug: CORT118335, dose to be determined

MAD Part 5 Placebo Cohort B

PLACEBO COMPARATOR

Drug: Placebo oral suspension

MAD Part 5 Active Cohort C

EXPERIMENTAL

CORT118335, dose to be determined

Drug: CORT118335, dose to be determined

MAD Part 5 Placebo Cohort C

PLACEBO COMPARATOR

Drug: Placebo oral suspension

Interventions

CORT118335, 25 mg DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Active Cohort A

Prednisone Oral Tablet DRUG

Challenge Agent, Dose and Route of Administration: Standard release 1x20mg and 1x5mg (25mg total) dose, orally administered.

SAD Part 2 Active PD Effect Cohort B: 630mg of CORT118335; SAD Part 2 Active PD Effect Cohort B: 675mg of CORT118335; SAD Part 2 Placebo PD Effect Cohort B

Glucose DRUG

75 g in 300 mL solution, orally administered

SAD Part 2 Active PD Effect Cohort B: 630mg of CORT118335; SAD Part 2 Active PD Effect Cohort B: 675mg of CORT118335; SAD Part 2 Placebo PD Effect Cohort B

Placebo oral suspension DRUG

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

MAD Part 5 Placebo Cohort A; MAD Part 5 Placebo Cohort B; MAD Part 5 Placebo Cohort C; SAD Part 4 Placebo Cohort A; SAD Part 4 Placebo Cohort B; SAD Part 4 Placebo Cohort C, Fasting; SAD Part 4 Placebo Cohort C, Fed; SAD Part 4 Placebo Cohort D

CORT118335, 75mg DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Active Cohort B

CORT118335, 225mg DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Active Cohort C

CORT118335, 675mg DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Active Cohort D; SAD Part 2 Active PD Effect Cohort B: 675mg of CORT118335

CORT118335, 600mg DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 2 Active Cohort A, Fasting; SAD Part 2 Active Cohort A, Fed

CORT118335, 630mg DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 2 Active PD Effect Cohort B: 630mg of CORT118335

CORT118335, 375mg DRUG

CORT118335 is supplied as capsules for oral dosing

MAD Part 3 Active Cohort A

CORT118335, 100mg DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Active Cohort A

CORT118335, 300mg DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Active Cohort B

CORT118335, 900mg DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Active Cohort C, Fasting; SAD Part 4 Active Cohort C, Fed

CORT118335, 150mg DRUG

CORT118335 is supplied as a suspension for oral dosing

MAD Part 5 Active Cohort A

CORT118335, 1500mg DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Active Cohort Part D

Placebo oral capsule DRUG

Placebo capsules, orally administered

MAD Part 3 Placebo Cohort A; SAD Part 1 Placebo Cohort B; SAD Part 1 Placebo Cohort C; SAD Part 1 Placebo Cohort D; SAD Part 1 Placebo oral capsule Cohort A; SAD Part 2 Placebo PD Effect Cohort B

CORT118335, dose to be determined DRUG

CORT118335 is supplied as suspension for oral dosing

MAD Part 5 Active Cohort B; MAD Part 5 Active Cohort C

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects or non-pregnant, non-lactating healthy female subjects of non-childbearing potential
• Age 18 to 60 years
• Body mass index (BMI) of 18.0 to 30.0 kg/m2
• Weight of ≤102 kg
• Must be willing and able to communicate and participate in the whole study
• Morning serum cortisol of 5 μg/dL to 23 μg/dL (138 nmol/L to 635 nmol/L) at screening and/or Day -1 for multiple dose cohorts
• Must provide written informed consent
• Must agree to use an adequate method of contraception
• Must agree to adhere to study restrictions

You may not qualify if:

• Subjects who have received any IMP in a clinical research study within the 3 months before the first dose in this study
• Subjects who are study site or Sponsor employees, or immediate family members of a study site or Sponsor employee
• Subjects who have previously been enrolled in this study
• Males who have a pregnant partner
• History of any drug or alcohol abuse in the year before the first dose in this study
• Regular alcohol consumption in male subjects \>21 units per week and female subjects \>14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
• Current smokers and those who have smoked within the 6 months before the first dose in this study. A breath carbon monoxide reading of greater than 10 ppm at screening or on admission
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the 6 months before the first dose in this study
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at screening
• Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the Investigator
• Positive drugs of abuse test result at screening or on admission (amphetamines, barbiturates, benzodiazepines, cocaine, marijuana/cannabis, methadone, methamphetamine/ecstasy, morphine/opiates, phencyclidine, tricyclic antidepressants)
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
• Subject has active renal and/or hepatic disease, as evidenced by:
• an estimated glomerular filtration rate (eGFR) of \<60 mL/min/1.73m2 using Modification of Diet in Renal Disease (MDRD) equation at screening
• ALT and/or AST \>1.5 times the upper limit of normal at screening or on admission

Sponsors & Collaborators

• Corcept Therapeutics: lead

Study Sites (1)

Quotient Clinical

Nottingham, Nottinghamshire, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

CORT118335; Prednisone; Glucose

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Stuart Mair, MBChB, MFPM

  Quotient Clinical

  PRINCIPAL INVESTIGATOR

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

Model Details: The 5 study parts may not be conducted entirely sequentially provided that this is justified by PK and safety data obtained from completed cohorts. The first MAD cohort will not start until data are available from at least 2 SAD levels using the same formulation.

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 20, 2017
• Study Start: September 15, 2017
• Primary Completion: February 22, 2019
• Study Completion: February 22, 2019
• Last Updated: May 24, 2019

Record last verified: 2019-05

Locations

GB (1)