First-in-human Study in Healthy Subjects

NCT ID: NCT03315338

Last Updated: 2019-05-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

143 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-15

Study Completion Date

2019-02-22

Brief Summary

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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.

Detailed Description

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This is a 5-part, single-center study of single and multiple ascending doses of CORT118335 in healthy subjects.

Parts I and 4 of the study are double-blind, randomized, placebo-controlled assessments of single-ascending doses (SAD) of CORT118335. Subjects will be enrolled sequentially into 1 of up 8 cohorts (Part 1, Cohorts A to D \[Cohorts E to G have been cancelled\]; Part 4, Cohorts A to D), each containing 8 subjects. Within each cohort, 6 subjects will be randomly assigned to receive a single dose of CORT118335 and 2 subjects will be randomly assigned to receive a single dose of matching placebo.

Part 2 Cohort A, food-effect, will be an open-label 2-way crossover study in one cohort of 12 subjects, randomized in a 1:1 ratio to receive a single dose of CORT118335 once after an overnight fast and once after a high-fat breakfast or the alternate sequence, over 2 study periods separated by a washout of at least 7 days/5 half-lives.

Part 2 Cohort B, PD cohort, will be a double-blind, randomized, placebo-controlled, 3-way cross-over study and will serve as proof of pharmacological effect (GR modulation) for CORT118335. Subjects will be randomized in a 1:1:1 ratio to receive placebo, and two dose levels of CORT118335 in one of three treatment sequences across 3 study periods separated by washouts of at least 7 days/5 half-lives. On each occasion, the ability of CORT118335 to ameliorate the pharmacological effects of a single dose of prednisone will be measured.

Parts 3 and 5 are double-blind, randomized, placebo-controlled assessments of multiple oral ascending doses of CORT118335. Subjects will be enrolled sequentially into 1 of up to 4 cohorts (Part 1 Cohort A \[Cohorts B to D have been cancelled; Part 5 Cohorts A to C), each containing 12 subjects. Within each cohort, 9 subjects will be randomly assigned to receive CORT118335 and 3 subjects to receive matching placebo daily for 14 days.

Different formulations of CORT118335 will be used in Parts 1, 2 and 3, and in Parts 4 and 5.

Conditions

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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SAD Part 1 Active Cohort A

CORT118335, 25 mg

Group Type EXPERIMENTAL

CORT118335, 25 mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Placebo oral capsule Cohort A

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Placebo capsules, orally administered

SAD Part 1 Active Cohort B

CORT118335, 75mg

Group Type EXPERIMENTAL

CORT118335, 75mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Placebo Cohort B

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Placebo capsules, orally administered

SAD Part 1 Active Cohort C

CORT118335, 225mg

Group Type EXPERIMENTAL

CORT118335, 225mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Placebo Cohort C

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Placebo capsules, orally administered

SAD Part 1 Active Cohort D

CORT118335, 675mg

Group Type EXPERIMENTAL

CORT118335, 675mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 1 Placebo Cohort D

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Placebo capsules, orally administered

SAD Part 2 Active Cohort A, Fasting

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

Group Type EXPERIMENTAL

CORT118335, 600mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 2 Active Cohort A, Fed

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

Group Type EXPERIMENTAL

CORT118335, 600mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

SAD Part 2 Placebo PD Effect Cohort B

Group Type PLACEBO_COMPARATOR

Prednisone Oral Tablet

Intervention Type DRUG

Challenge Agent, Dose and Route of Administration:

Standard release 1x20mg and 1x5mg (25mg total) dose, orally administered.

Glucose

Intervention Type DRUG

75 g in 300 mL solution, orally administered

Placebo oral capsule

Intervention Type DRUG

Placebo capsules, orally administered

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

Group Type EXPERIMENTAL

Prednisone Oral Tablet

Intervention Type DRUG

Challenge Agent, Dose and Route of Administration:

Standard release 1x20mg and 1x5mg (25mg total) dose, orally administered.

Glucose

Intervention Type DRUG

75 g in 300 mL solution, orally administered

CORT118335, 630mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

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

Group Type EXPERIMENTAL

Prednisone Oral Tablet

Intervention Type DRUG

Challenge Agent, Dose and Route of Administration:

Standard release 1x20mg and 1x5mg (25mg total) dose, orally administered.

Glucose

Intervention Type DRUG

75 g in 300 mL solution, orally administered

CORT118335, 675mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

MAD Part 3 Active Cohort A

CORT118335, 375mg qd for 14 days

Group Type EXPERIMENTAL

CORT118335, 375mg

Intervention Type DRUG

CORT118335 is supplied as capsules for oral dosing

MAD Part 3 Placebo Cohort A

Placebo qd for 14 days

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Placebo capsules, orally administered

SAD Part 4 Active Cohort A

CORT118335, 100mg

Group Type EXPERIMENTAL

CORT118335, 100mg

Intervention Type DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Placebo Cohort A

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

SAD Part 4 Active Cohort B

CORT118335, 300mg

Group Type EXPERIMENTAL

CORT118335, 300mg

Intervention Type DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Placebo Cohort B

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

SAD Part 4 Active Cohort C, Fasting

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

Group Type EXPERIMENTAL

CORT118335, 900mg

Intervention Type DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Active Cohort C, Fed

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

Group Type EXPERIMENTAL

CORT118335, 900mg

Intervention Type DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Placebo Cohort C, Fasting

Supplied as suspension for oral dosing given after an overnight fast

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

SAD Part 4 Placebo Cohort C, Fed

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

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

SAD Part 4 Active Cohort Part D

CORT118335, 1500mg

Group Type EXPERIMENTAL

CORT118335, 1500mg

Intervention Type DRUG

CORT118335 is supplied as a suspension for oral dosing

SAD Part 4 Placebo Cohort D

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

MAD Part 5 Active Cohort A

CORT118335, 150mg

Group Type EXPERIMENTAL

CORT118335, 150mg

Intervention Type DRUG

CORT118335 is supplied as a suspension for oral dosing

MAD Part 5 Placebo Cohort A

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

MAD Part 5 Active Cohort B

CORT118335, dose to be determined

Group Type EXPERIMENTAL

CORT118335, dose to be determined

Intervention Type DRUG

CORT118335 is supplied as suspension for oral dosing

MAD Part 5 Placebo Cohort B

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

MAD Part 5 Active Cohort C

CORT118335, dose to be determined

Group Type EXPERIMENTAL

CORT118335, dose to be determined

Intervention Type DRUG

CORT118335 is supplied as suspension for oral dosing

MAD Part 5 Placebo Cohort C

Group Type PLACEBO_COMPARATOR

Placebo oral suspension

Intervention Type DRUG

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

Interventions

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CORT118335, 25 mg

CORT118335 is supplied as capsules for oral dosing

Intervention Type DRUG

Prednisone Oral Tablet

Challenge Agent, Dose and Route of Administration:

Standard release 1x20mg and 1x5mg (25mg total) dose, orally administered.

Intervention Type DRUG

Glucose

75 g in 300 mL solution, orally administered

Intervention Type DRUG

Placebo oral suspension

Reference Therapy, Dose and Route of Administration:

Placebo suspension, orally administered.

Intervention Type DRUG

CORT118335, 75mg

CORT118335 is supplied as capsules for oral dosing

Intervention Type DRUG

CORT118335, 225mg

CORT118335 is supplied as capsules for oral dosing

Intervention Type DRUG

CORT118335, 675mg

CORT118335 is supplied as capsules for oral dosing

Intervention Type DRUG

CORT118335, 600mg

CORT118335 is supplied as capsules for oral dosing

Intervention Type DRUG

CORT118335, 630mg

CORT118335 is supplied as capsules for oral dosing

Intervention Type DRUG

CORT118335, 375mg

CORT118335 is supplied as capsules for oral dosing

Intervention Type DRUG

CORT118335, 100mg

CORT118335 is supplied as a suspension for oral dosing

Intervention Type DRUG

CORT118335, 300mg

CORT118335 is supplied as a suspension for oral dosing

Intervention Type DRUG

CORT118335, 900mg

CORT118335 is supplied as a suspension for oral dosing

Intervention Type DRUG

CORT118335, 150mg

CORT118335 is supplied as a suspension for oral dosing

Intervention Type DRUG

CORT118335, 1500mg

CORT118335 is supplied as a suspension for oral dosing

Intervention Type DRUG

Placebo oral capsule

Placebo capsules, orally administered

Intervention Type DRUG

CORT118335, dose to be determined

CORT118335 is supplied as suspension for oral dosing

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* subjects with borderline results can have these tests repeated once.
* History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, gastrointestinal or neurological disease as judged by the Investigator
* Subject had any form of cancer within the 2 years before first dose in this study\*, with the exception of basal cell and/or squamous cell cancer of the skin that has been treated completely and is without evidence of local recurrence or metastasis
* Subject has a history and/or symptoms of adrenal insufficiency
* Subject has consumed liquorice or other glycyrrhetic acid derivatives regularly, in the judgement of the Investigator, in the 6 months before the first dose of study medication
* Subject has a history of jaundice and/or subject has had a cholecystectomy
* Subject has a history of clinically significant gastrointestinal disease including gastroesophageal reflux disease, malabsorption syndrome, colon cancer, chronic colitis, Crohn's disease, inflammatory bowel disease, gastroparesis, constipation, chronic diarrhoea, obstruction, gastrointestinal bleeding, and/or peptic ulcers
* Subject has a condition that could be aggravated by glucocorticoid and/or mineralocorticoid blockade (e.g., asthma, any chronic inflammatory condition) or activation (e.g., 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
* Subjects with a QTcF interval of \>450 msec at screening or pre-dose, based on the mean of three ECGs
* History of additional risk factors for torsades de pointes (e.g., heart failure, hypokalaemia, family history of long QT syndrome)
* Supine heart rate at rest of \<40 bpm or \>100 bpm. BP out with the following ranges: diastolic BP 40-90; systolic BP 90-140 (subjects aged 18-45 year) and 90-160 (subjects aged \>45 year). Heart rate and blood pressure can be retested twice in the supine position at intervals of 5 min on a given day at screening and admission.
* Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients including glucose/fructose intolerance for the standard oral glucose tolerance test (OGTT)
* Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator.
* Donation or loss of greater than 400 mL of blood within the 3 months before first study dose
* Subjects who are taking, or have taken, any prescribed, over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies within 14 days, or for which 5 times the medication's elimination half-life will not be completed if longer, before the first dose of study medication. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the Investigator and Sponsor's medical monitor. Standard dose multivitamins are permitted throughout the study period
* Subjects who are currently using glucocorticoids or have a history of systemic glucocorticoid use at any dose within the last 12 months or 3 months for inhaled products
* Subjects who are taking, or have taken enzyme inducers within 30 days before the first dose of study medication
* Subject is expected to require use of any medication (with the exception of standard dose multivitamins) during the study period
* Subject has a history or presence of any medical condition or disease which, in the opinion of the Investigator, could interfere with the conduct of the study or could put the subject at unacceptable risk. This specifically includes any subject with flu or flu-like symptoms
* Failure to satisfy the Investigator of fitness to participate for any other reason
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Corcept Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stuart Mair, MBChB, MFPM

Role: PRINCIPAL_INVESTIGATOR

Quotient Clinical

Locations

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Quotient Clinical

Nottingham, Nottinghamshire, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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CORT118335-850

Identifier Type: -

Identifier Source: org_study_id

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