Drug-Drug Interaction Study of Atumelnant in Healthy Participants

A Phase 1, Open-Label, Two-Cohort Study to Assess the Effect of a Strong CYP3A4 Inducer on the Pharmacokinetics of Atumelnant and the Effect of Atumelnant on the Pharmacokinetics of CYP3A4, P-gp, and MATE1/2-K Substrates in Healthy Participants

This study aims to evaluate the impact of strong CYP3A4 induction on the pharmacokinetics (PK) of atumelnant, as well as the effect of atumelnant on CYP3A4, P-gp, and MATE1/2-K substrates in healthy participants.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Digoxin; Drug: Atumelnant; Drug: Carbamazepine; Drug: Midazolam; Drug: Metformin

Detailed Description

This is a Phase 1, open-label, two-Cohort Study to assess the effect of a strong CYP3A4 inducer on the pharmacokinetics of atumelnant and the effect of atumelnant on the pharmacokinetics of CYP3A4, P-gp, and MATE1/2-K Substrates in healthy participants.

Approximately 20 healthy male and female participants adult male and female (of non-childbearing potential) participants will be enrolled in Cohort 1. Approximately 26 healthy male and female participants adult male and female (of non-childbearing potential) participants will be enrolled in Cohort 2.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Crinetics Clinical Trials; Phone Number: 833-827-9741; Email: clinicaltrials@crinetics.com

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Recruiting
      • Crinetics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy adult females of non-childbearing potential (Section 14.2) or healthy adult males, 19-55 years of age, inclusive, at the screening visit.
2. BMI ≥18.0 and ≤32.0 kg/m2 at the screening visit.
3. Is willing and able to comply with all study procedures and restrictions, including fasting and consumption of protocol-specified standardized meal for required study measurements; inpatient admission; follow-up contact; receipt of rescue therapy, if necessary; abstinence from tobacco, alcohol, drugs, and from strenuous unaccustomed exercise and sports (defined as greater than 30 minutes per day) during the study period.
4. Normal adrenocorticotropic hormone (ACTH)-stimulated cortisol test at the screening visit and does not have signs and symptoms of adrenal insufficiency as deemed by the PI or designee.

Exclusion Criteria:

1. Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
3. Female participant with a positive pregnancy test at the screening visit or at first check-in or who is lactating.
4. Female participant of childbearing potential.
5. Had prior treatment with atumelnant.
6. Participation in another clinical study within 30 days or received any investigational drug within 5 half-lives prior to the first dosing, whichever is longer. The time window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study.
7. History or presence of hypersensitivity or idiosyncratic reaction to the study interventions or related compounds.
8. Has a blood loss ≥500 mL or donated blood within 3 months prior to the first dosing.
9. Unable to refrain from or anticipates the use of any drugs, including prescription and non-prescription medications, herbal remedies, vitamin supplements, or other food supplements within 14 days or 5 half-lives prior to the first dosing, whichever is longer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; atumelnant, carbamazepine (CYP3A4 Inducer)	Drug: Atumelnant; Atumelnant, tablets; Other Names: CRN04894; Drug: Carbamazepine; CYP3A4 inducer
Experimental: Cohort 2; atumelnant, midazolam (CYP3A4 substrate), digoxin (P-gp substrate), metformin (MATE1/2-K substrate)	Drug: Digoxin; P-gp substrate; Drug: Atumelnant; Atumelnant, tablets; Other Names: CRN04894; Drug: Midazolam; CYP3A4 substrate; Drug: Metformin; MATE1/2-K substrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cohort 1: Pharmacokinetics (AUC 0-last)	Up to Day 34
Cohort 1: Pharmacokinetics (AUC 0-inf)	Up to Day 34
Cohort 1: Pharmacokinetics (Cmax)	Up to Day 34
Cohort 2: Pharmacokinetics (AUC 0-last)	Up to Day 21
Cohort 2: Pharmacokinetics (AUC 0-inf)	Up to Day 21
Cohort 2: Pharmacokinetics (Cmax)	Up to Day 21

Secondary Outcome Measures

Outcome Measure	Time Frame
Cohort 1: Number of participants with Treatment Emergent Adverse Events	Up to Day 34
Cohort 2: Number of participants with Treatment Emergent Adverse Events	Up to Day 21

Collaborators and Investigators

• Sponsor: Crinetics Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 6, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 29, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Healthy volunteers; CRN04894; Atumelnant
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Polycyclic Compounds; Glycosides; Steroids; Fused-Ring Compounds; Benzazepines; Biguanides; Guanidines; Amidines; Benzodiazepines; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Midazolam; Digoxin; Metformin; Carbamazepine
• Other Study ID Numbers: CRN04894-131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No