Healthy Volunteers
Conditions
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.
Interventions
DRUGCRN00808
Investigational drug
Placebo
Midazolam as part of the drug-drug interaction arm of the study
DRUGPlacebo oral capsule
Placebo
Sponsors
Crinetics Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind study
Intervention model description
Single and multiple-dose cohorts are placebo-controlled. The midazolam cohort does not have placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| t1/2 of CRN00808 single ascending doses | Day 1 through Day 7 | plasma t1/2 |
| Tmax of CRN00808 single ascending doses | Day 1 through Day 7 | plasma Tmax |
| AUC of CRN00808 multiple ascending doses | Day 1 through Day 20 | plasma AUC |
| Cmax of CRN00808 multiple ascending doses | Day 1 through Day 20 | plasma Cmax |
| t1/2 of CRN00808 multiple ascending doses | Day 1 through Day 20 | plasma t1/2 |
| Tmax of CRN00808 multiple ascending doses | Day 1 through Day 20 | plasma Tmax |
| 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 |
| AUC of CRN00808 single ascending doses | Day 1 through Day 7 | plasma AUC |
| Effect of CRN00808 on Cmax of midazolam | Day 1 through Day 10 | midazolam plasma Cmax |
| 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 |
| 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 |
| Effect of food on AUC of CRN00808 | Day 1 to Day 7 | Plasma AUC 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 |
| Effect of CRN00808 on pharmacokinetics of midazolam | Day 1 through Day 10 | midazolam plasma AUC |
| Cmax of CRN00808 single ascending doses | Day 1 through Day 7 | plasma Cmax |
Countries
Australia
Outcome results
None listed