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

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.

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