Single and Multiple-Ascending Dose Study of CRN00808 in Healthy Volunteers

Crinetics Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo oral capsule; Drug: Midazolam oral solution; Drug: CRN00808; Drug: Placebo Oral Solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT03276858

CRN00808-01

Details and patient eligibility

About

This single-center study will be conducted in 3 phases: a single-ascending dose phase (up to 8 cohorts, 8 subjects/cohort), a multiple-dose phase (up to 5 cohorts, 9 subjects/cohort), and a midazolam drug-drug interaction phase (one cohort of 8 subjects).

Full description

The single-dose phase initiates with ascending doses of an oral solution followed by a 3-way crossover food effect and bioavailability (capsule formulation) cohort. Serum IGF-1 levels and GHRH-analog stimulated GH levels will be assessed as pharmacodynamics measures.

The first multiple-dose (7 days dosing) cohort will be initiated after the PK and safety data are available from the single-dose phase. Subsequent multiple-dose cohorts will have 10 days of dosing. Serum IGF-1 level and GH levels will be assessed as pharmacodynamics measures.

The last cohort in the study is midazolam drug-drug interaction study. The dose will be selected based on review of all pharmacokinetic and safety data for the single-dose and multiple-dose cohorts completed. On Day 1, 8 subjects will receive a single oral 2 mg dose of midazolam. Starting on Day 3 through Day 8, subjects will receive daily doses of CRN00808. On Day 9, subjects will be administered CRN00808 and 2 mg midazolam together.

Enrollment: 99 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• BMI 18 to 30 kg/m2
• Females postmenopausal or surgically sterile

Exclusion criteria

• Any uncontrolled or active major systemic disease including, but not limited to: acromegaly (with or without pituitary surgery or radiation therapy), cardiac, pulmonary, gastrointestinal, metabolic, urogenital, neurological, immunological, psychiatric, or neoplastic disorder with metastatic potential
• History or presence of malignancy within the past 5 years. Subjects who have been successfully treated (for 3 months or longer) with no recurrence of basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled.
• Use of any investigational drug within the past 60 days or 5 half-lives, whichever is longer
• Have a medically significant abnormality observed during screening or the admission physical examination or in any other baseline measurements
• Use of any prior medication without approval of the investigator within 14 days prior to admission
• Tested positive at screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab) or has a history of a positive result
• History of alcohol or substance abuse in the past 6 months
• Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this Phase 1 study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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99 participants in 5 patient groups, including a placebo group

CRN00808 Oral Solution

Experimental group

Description:

CRN00808 oral solution, single-dose

Treatment:

Drug: CRN00808

CRN00808 Oral Capsule

Experimental group

Description:

CRN00808 oral capsule, single-dose and multiple-doses

Treatment:

Drug: CRN00808

Placebo Oral Solution

Placebo Comparator group

Description:

Placebo oral solution, single-dose

Treatment:

Drug: Placebo Oral Solution

Placebo Oral Capsule

Placebo Comparator group

Description:

Placebo oral capsule, single-dose and multiple doses

Treatment:

Drug: Placebo oral capsule

Midazolam Oral Solution

Other group

Description:

Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study

Treatment:

Drug: CRN00808

Drug: Midazolam oral solution