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

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ClinicalTrials.gov Identifier: NCT03276858
Recruitment Status : Completed
First Posted : September 8, 2017
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Crinetics Pharmaceuticals Inc.

September 5, 2017
September 8, 2017
August 29, 2018
September 22, 2017
April 30, 2018   (Final data collection date for primary outcome measure)
  • 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 [ Time Frame: 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 [ Time Frame: Day 1 through Day 21 ]
    ECG, clinical laboratory parameters, vital signs, physical examinations
  • 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 [ Time Frame: Day 1 through Day 7 ]
    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 [ Time Frame: Day 1 through Day 14 ]
    ECG, clinical laboratory parameters, vital signs, physical examinations
Complete list of historical versions of study NCT03276858 on ClinicalTrials.gov Archive Site
  • AUC of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma AUC
  • Cmax of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma Cmax
  • t1/2 of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma t1/2
  • Tmax of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma Tmax
  • AUC of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma AUC
  • Cmax of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma Cmax
  • t1/2 of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma t1/2
  • Tmax of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma Tmax
  • Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels [ Time Frame: Day -1 and Day 1 ]
    Suppression of serum GH induced by a GH secretagogue
  • Effect of CRN00808 on pharmacokinetics of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma AUC
  • Effect of CRN00808 on Cmax of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma Cmax
  • Effect of CRN00808 on t1/2 of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma t 1/2
  • Effect of CRN00808 on Tmax of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma Tmax
  • Relative bioavailability of capsule formulation [ Time Frame: Day 1 to Day 7 ]
    single-dose crossover arm only
  • Effect of food on Cmax of CRN00808 [ Time Frame: Day 1 to Day 7 ]
    plasma Cmax compared with and without food in single dose arm
  • Effect of food on AUC of CRN00808 [ Time Frame: 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 [ Time Frame: Day -1 to Day 21 ]
    serum IGF-1 and GH
  • AUC of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma AUC
  • Cmax of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma Cmax
  • t1/2 of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma t1/2
  • Tmax of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma Tmax
  • AUC of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 13 ]
    plasma AUC
  • Cmax of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 13 ]
    plasma Cmax
  • t1/2 of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 13 ]
    plasma t1/2
  • Tmax of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 13 ]
    plasma Tmax
  • Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels [ Time Frame: Day -1 and Day 1 ]
    Suppression of serum GH induced by a GH secretagogue
  • Effect of CRN00808 on pharmacokinetics of midazolam [ Time Frame: Day 1 through Day 9 ]
    midazolam plasma AUC
  • Effect of CRN00808 on Cmax of midazolam [ Time Frame: Day 1 through Day 9 ]
    midazolam plasma Cmax
  • Effect of CRN00808 on t1/2 of midazolam [ Time Frame: Day 1 through Day 9 ]
    midazolam plasma t 1/2
  • Effect of CRN00808 on Tmax of midazolam [ Time Frame: Day 1 through Day 9 ]
    midazolam plasma Tmax
  • Relative bioavailability of capsule formulation [ Time Frame: Day 1 to Day 7 ]
    single-dose crossover arm only
  • Effect of food on Cmax of CRN00808 [ Time Frame: Day 1 to Day 7 ]
    plasma Cmax compared with and without food in single dose arm
  • Effect of food on AUC of CRN00808 [ Time Frame: 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 [ Time Frame: Day -1 to Day 14 ]
    serum IGF-1 and GH
Not Provided
Not Provided
 
Single and Multiple-Ascending Dose Study of CRN00808 in Healthy Volunteers
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
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).

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.

Interventional
Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Single and multiple-dose cohorts are placebo-controlled. The midazolam cohort does not have placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind study
Primary Purpose: Treatment
Healthy Volunteers
  • Drug: CRN00808
    Investigational drug
  • Drug: Placebo Oral Solution
    Placebo
  • Drug: Midazolam oral solution
    Midazolam as part of the drug-drug interaction arm of the study
  • Drug: Placebo oral capsule
    Placebo
  • Experimental: CRN00808 Oral Solution
    CRN00808 oral solution, single-dose
    Intervention: Drug: CRN00808
  • Experimental: CRN00808 Oral Capsule
    CRN00808 oral capsule, single-dose and multiple-doses
    Intervention: Drug: CRN00808
  • Placebo Comparator: Placebo Oral Solution
    Placebo oral solution, single-dose
    Intervention: Drug: Placebo Oral Solution
  • Placebo Comparator: Placebo Oral Capsule
    Placebo oral capsule, single-dose and multiple doses
    Intervention: Drug: Placebo oral capsule
  • Midazolam Oral Solution
    Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study
    Interventions:
    • Drug: CRN00808
    • Drug: Midazolam oral solution
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
99
83
April 30, 2018
April 30, 2018   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 50 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
Australia
 
 
NCT03276858
CRN00808-01
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Crinetics Pharmaceuticals Inc.
Crinetics Pharmaceuticals Inc.
Not Provided
Principal Investigator: Jason Lickliter, MBBS PhD Nucleus Network
Crinetics Pharmaceuticals Inc.
August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP