Single and Multiple-Ascending Dose Study of CRN00808 in Healthy Volunteers
- Conditions
- Healthy Volunteers
- Interventions
- Registration Number
- NCT03276858
- Lead Sponsor
- Crinetics Pharmaceuticals Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 99
- BMI 18 to 30 kg/m2
- Females postmenopausal or surgically sterile
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CRN00808 Oral Solution CRN00808 CRN00808 oral solution, single-dose CRN00808 Oral Capsule CRN00808 CRN00808 oral capsule, single-dose and multiple-doses Placebo Oral Solution Placebo Oral Solution Placebo oral solution, single-dose Placebo Oral Capsule Placebo oral capsule Placebo oral capsule, single-dose and multiple doses Midazolam Oral Solution CRN00808 Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study Midazolam Oral Solution Midazolam oral solution Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 single ascending doses using clinical assessments, telemetry, and Holter monitoring and subject self-reporting Day 1 through Day 10 ECG, clinical laboratory parameters, vital signs, physical examinations, telemetry, Holter monitoring
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 multiple ascending doses using clinical assessments and subject self-reporting Day 1 through Day 21 ECG, clinical laboratory parameters, vital signs, physical examinations
- Secondary Outcome Measures
Name Time Method AUC of CRN00808 single ascending doses Day 1 through Day 7 plasma AUC
Cmax of CRN00808 multiple ascending doses Day 1 through Day 20 plasma Cmax
Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels Day -1 and Day 1 Suppression of serum GH induced by a GH secretagogue
Effect of CRN00808 on pharmacokinetics of midazolam Day 1 through Day 10 midazolam plasma AUC
Effect of CRN00808 on Cmax of midazolam Day 1 through Day 10 midazolam plasma Cmax
Tmax of CRN00808 multiple ascending doses Day 1 through Day 20 plasma Tmax
Tmax of CRN00808 single ascending doses Day 1 through Day 7 plasma Tmax
Relative bioavailability of capsule formulation Day 1 to Day 7 single-dose crossover arm only
Effect of food on Cmax of CRN00808 Day 1 to Day 7 plasma Cmax compared with and without food in single dose arm
Pharmacodynamics of CRN00808 in multiple ascending dose cohorts assessed by serum IGF-1 and GH Day -1 to Day 21 serum IGF-1 and GH
AUC of CRN00808 multiple ascending doses Day 1 through Day 20 plasma AUC
t1/2 of CRN00808 multiple ascending doses Day 1 through Day 20 plasma t1/2
Cmax of CRN00808 single ascending doses Day 1 through Day 7 plasma Cmax
t1/2 of CRN00808 single ascending doses Day 1 through Day 7 plasma t1/2
Effect of CRN00808 on t1/2 of midazolam Day 1 through Day 10 midazolam plasma t 1/2
Effect of CRN00808 on Tmax of midazolam Day 1 through Day 10 midazolam plasma Tmax
Effect of food on AUC of CRN00808 Day 1 to Day 7 Plasma AUC compared with and without food in single dose arm
Trial Locations
- Locations (1)
Nucleus Network
🇦🇺Melbourne, Victoria, Australia