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Trial record 1 of 1 for:    CRN00808
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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.

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).

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: CRN00808 Drug: Placebo Oral Solution Drug: Midazolam oral solution Drug: Placebo oral capsule Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
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
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
Actual Study Start Date : September 22, 2017
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CRN00808 Oral Solution
CRN00808 oral solution, single-dose
Drug: CRN00808
Investigational drug

Experimental: CRN00808 Oral Capsule
CRN00808 oral capsule, single-dose and multiple-doses
Drug: CRN00808
Investigational drug

Placebo Comparator: Placebo Oral Solution
Placebo oral solution, single-dose
Drug: Placebo Oral Solution
Placebo

Placebo Comparator: Placebo Oral Capsule
Placebo oral capsule, single-dose and multiple doses
Drug: Placebo oral capsule
Placebo

Midazolam Oral Solution
Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study
Drug: CRN00808
Investigational drug

Drug: Midazolam oral solution
Midazolam as part of the drug-drug interaction arm of the study




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. AUC of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma AUC

  2. Cmax of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma Cmax

  3. t1/2 of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma t1/2

  4. Tmax of CRN00808 single ascending doses [ Time Frame: Day 1 through Day 7 ]
    plasma Tmax

  5. AUC of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma AUC

  6. Cmax of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma Cmax

  7. t1/2 of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma t1/2

  8. Tmax of CRN00808 multiple ascending doses [ Time Frame: Day 1 through Day 20 ]
    plasma Tmax

  9. 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

  10. Effect of CRN00808 on pharmacokinetics of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma AUC

  11. Effect of CRN00808 on Cmax of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma Cmax

  12. Effect of CRN00808 on t1/2 of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma t 1/2

  13. Effect of CRN00808 on Tmax of midazolam [ Time Frame: Day 1 through Day 10 ]
    midazolam plasma Tmax

  14. Relative bioavailability of capsule formulation [ Time Frame: Day 1 to Day 7 ]
    single-dose crossover arm only

  15. 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

  16. 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

  17. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03276858


Locations
Australia, Victoria
Nucleus Network
Melbourne, Victoria, Australia
Sponsors and Collaborators
Crinetics Pharmaceuticals Inc.
Investigators
Principal Investigator: Jason Lickliter, MBBS PhD Nucleus Network

Responsible Party: Crinetics Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03276858     History of Changes
Other Study ID Numbers: CRN00808-01
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Pharmaceutical Solutions
Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action