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

NCT ID: NCT03276858

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-22
• Study Completion Date: 2018-04-30

Brief Summary

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).

Detailed 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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CRN00808 Oral Solution

CRN00808 oral solution, single-dose

Group Type: EXPERIMENTAL

CRN00808

Intervention Type: DRUG

Investigational drug

CRN00808 Oral Capsule

CRN00808 oral capsule, single-dose and multiple-doses

Group Type: EXPERIMENTAL

CRN00808

Intervention Type: DRUG

Investigational drug

Placebo Oral Solution

Placebo oral solution, single-dose

Group Type: PLACEBO_COMPARATOR

Placebo Oral Solution

Intervention Type: DRUG

Placebo

Placebo Oral Capsule

Placebo oral capsule, single-dose and multiple doses

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Placebo

Midazolam Oral Solution

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

Group Type: OTHER

CRN00808

Intervention Type: DRUG

Investigational drug

Midazolam oral solution

Intervention Type: DRUG

Midazolam as part of the drug-drug interaction arm of the study

Interventions

CRN00808

Investigational drug

Intervention Type: DRUG

Placebo Oral Solution

Placebo

Intervention Type: DRUG

Midazolam oral solution

Midazolam as part of the drug-drug interaction arm of the study

Intervention Type: DRUG

Placebo oral capsule

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Crinetics Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jason Lickliter, MBBS PhD

Role: PRINCIPAL_INVESTIGATOR

Nucleus Network

Locations

Nucleus Network

Melbourne, Victoria, Australia

Countries

Australia

References

Madan A, Markison S, Betz SF, Krasner A, Luo R, Jochelson T, Lickliter J, Struthers RS. Paltusotine, a novel oral once-daily nonpeptide SST2 receptor agonist, suppresses GH and IGF-1 in healthy volunteers. Pituitary. 2022 Apr;25(2):328-339. doi: 10.1007/s11102-021-01201-z. Epub 2022 Jan 9.

Reference Type: DERIVED

PMID: 35000098 (View on PubMed)

Other Identifiers

CRN00808-01

Identifier Type: -

Identifier Source: org_study_id