CompletedNCT03276858Updated Aug 29, 2018

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

A Phase 1 interventional study of CRN00808 and Placebo Oral Solution in Healthy Volunteers, sponsored by Crinetics Pharmaceuticals Inc.. Completed at 1 site in Australia. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-08-29.

Sponsored by Crinetics Pharmaceuticals Inc. · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 99
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: All

Study 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).

Read the 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.

Conditions studied

Healthy Volunteers

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

BMI 18 to 30 kg/m2
Females postmenopausal or surgically sterile

Exclusion criteria

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 99 participants (actual)

Study arms

Experimental
CRN00808 Oral Solution
CRN00808 oral solution, single-dose
Drug: CRN00808
Experimental
CRN00808 Oral Capsule
CRN00808 oral capsule, single-dose and multiple-doses
Drug: CRN00808
Placebo comparator
Placebo Oral Solution
Placebo oral solution, single-dose
Drug: Placebo Oral Solution
Placebo comparator
Placebo Oral Capsule
Placebo oral capsule, single-dose and multiple doses
Drug: Placebo oral capsule
Other
Midazolam Oral Solution
Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study
Drug: CRN00808 · Drug: Midazolam oral solution

Interventions

DrugCRN00808
Investigational drug
DrugPlacebo Oral Solution
Placebo
DrugMidazolam oral solution
Midazolam as part of the drug-drug interaction arm of the study
DrugPlacebo oral capsule
Placebo

What researchers measure

Primary outcomes

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
Time frame: Day 1 through Day 10
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
Time frame: Day 1 through Day 21

Secondary outcomes

AUC of CRN00808 single ascending doses
plasma AUC
Time frame: Day 1 through Day 7
Cmax of CRN00808 single ascending doses
plasma Cmax
Time frame: Day 1 through Day 7
t1/2 of CRN00808 single ascending doses
plasma t1/2
Time frame: Day 1 through Day 7
Tmax of CRN00808 single ascending doses
plasma Tmax
Time frame: Day 1 through Day 7
AUC of CRN00808 multiple ascending doses
plasma AUC
Time frame: Day 1 through Day 20
Cmax of CRN00808 multiple ascending doses
plasma Cmax
Time frame: Day 1 through Day 20
t1/2 of CRN00808 multiple ascending doses
plasma t1/2
Time frame: Day 1 through Day 20
Tmax of CRN00808 multiple ascending doses
plasma Tmax
Time frame: Day 1 through Day 20
Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels
Suppression of serum GH induced by a GH secretagogue
Time frame: Day -1 and Day 1
Effect of CRN00808 on pharmacokinetics of midazolam
midazolam plasma AUC
Time frame: Day 1 through Day 10
Effect of CRN00808 on Cmax of midazolam
midazolam plasma Cmax
Time frame: Day 1 through Day 10
Effect of CRN00808 on t1/2 of midazolam
midazolam plasma t 1/2
Time frame: Day 1 through Day 10
Effect of CRN00808 on Tmax of midazolam
midazolam plasma Tmax
Time frame: Day 1 through Day 10
Relative bioavailability of capsule formulation
single-dose crossover arm only
Time frame: Day 1 to Day 7
Effect of food on Cmax of CRN00808
plasma Cmax compared with and without food in single dose arm
Time frame: Day 1 to Day 7
Effect of food on AUC of CRN00808
Plasma AUC compared with and without food in single dose arm
Time frame: Day 1 to Day 7
Pharmacodynamics of CRN00808 in multiple ascending dose cohorts assessed by serum IGF-1 and GH
serum IGF-1 and GH
Time frame: Day -1 to Day 21

Study locations

1 site

Nucleus Network
Melbourne, Victoria, Australia

References and documents

Publications

Madan A, Markison S, Betz SF, Krasner A, Luo R, Jochelson T, Lickliter J, Struthers RS. Paltusotine, a novel oral once-daily nonpeptide SST2 receptor agonist, suppresses GH and IGF-1 in healthy volunteers. Pituitary. 2022 Apr;25(2):328-339. doi: 10.1007/s11102-021-01201-z. Epub 2022 Jan 9. PubMed 35000098 ↗

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03276858
Lead sponsor: Crinetics Pharmaceuticals Inc.
Responsible party: Sponsor
First posted: Sep 8, 2017
Start date: Sep 22, 2017
Primary completion: Apr 30, 2018
Completion: Apr 30, 2018
Last update: Aug 29, 2018

Study contacts

Jason Lickliter, MBBS PhD

principal investigator · Nucleus Network

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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