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

Healthy Volunteers Clinical Trial

Official title:

A Double-Blind, Randomized, Placebo-Controlled, Single- And-Multiple-Dose Study to Evaluate the Safety, PK, and PD of CRN00808 in Healthy Volunteers and to Determine the Effect of CRN00808 on Midazolam PK

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03276858
• Other study ID #: CRN00808-01
• Status: Completed
• Phase: Phase 1
• Start date: September 22, 2017
• Est. completion date: April 30, 2018

Study information

• Verified date: August 2018
• Source: Crinetics Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: April 30, 2018
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• CRN00808
Investigational drug
• Placebo Oral Solution
Placebo
• Midazolam oral solution
Midazolam as part of the drug-drug interaction arm of the study
• Placebo oral capsule
Placebo

Locations

Country	Name	City	State
Australia	Nucleus Network	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Crinetics Pharmaceuticals Inc.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	ECG, clinical laboratory parameters, vital signs, physical examinations, telemetry, Holter monitoring	Day 1 through Day 10
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 multiple ascending doses using clinical assessments and subject self-reporting	ECG, clinical laboratory parameters, vital signs, physical examinations	Day 1 through Day 21
Secondary	AUC of CRN00808 single ascending doses	plasma AUC	Day 1 through Day 7
Secondary	Cmax of CRN00808 single ascending doses	plasma Cmax	Day 1 through Day 7
Secondary	t1/2 of CRN00808 single ascending doses	plasma t1/2	Day 1 through Day 7
Secondary	Tmax of CRN00808 single ascending doses	plasma Tmax	Day 1 through Day 7
Secondary	AUC of CRN00808 multiple ascending doses	plasma AUC	Day 1 through Day 20
Secondary	Cmax of CRN00808 multiple ascending doses	plasma Cmax	Day 1 through Day 20
Secondary	t1/2 of CRN00808 multiple ascending doses	plasma t1/2	Day 1 through Day 20
Secondary	Tmax of CRN00808 multiple ascending doses	plasma Tmax	Day 1 through Day 20
Secondary	Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels	Suppression of serum GH induced by a GH secretagogue	Day -1 and Day 1
Secondary	Effect of CRN00808 on pharmacokinetics of midazolam	midazolam plasma AUC	Day 1 through Day 10
Secondary	Effect of CRN00808 on Cmax of midazolam	midazolam plasma Cmax	Day 1 through Day 10
Secondary	Effect of CRN00808 on t1/2 of midazolam	midazolam plasma t 1/2	Day 1 through Day 10
Secondary	Effect of CRN00808 on Tmax of midazolam	midazolam plasma Tmax	Day 1 through Day 10
Secondary	Relative bioavailability of capsule formulation	single-dose crossover arm only	Day 1 to Day 7
Secondary	Effect of food on Cmax of CRN00808	plasma Cmax compared with and without food in single dose arm	Day 1 to Day 7
Secondary	Effect of food on AUC of CRN00808	Plasma AUC compared with and without food in single dose arm	Day 1 to Day 7
Secondary	Pharmacodynamics of CRN00808 in multiple ascending dose cohorts assessed by serum IGF-1 and GH	serum IGF-1 and GH	Day -1 to Day 21