Study of the Effects of Itraconazole and Carbamazepine on LY3410738 in Healthy Participants

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05205447

Collaborator

Loxo Oncology, Inc. (Industry)

Enrollment

Location

Arms

11.9

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to learn about how itraconazole and carbamazepine affect the levels of LY3410738 in the blood stream of healthy participants. Participation could last up to 75 days.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: LY3410738 Drug: Itraconazole Drug: Carbamazepine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

27 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Phase 1, Two-part, Open-label, Fixed-sequence Study to Evaluate the Effects of Multiple Doses of Itraconazole and Carbamazepine on the Single-dose Pharmacokinetics of LY3410738 in Healthy Adult Subjects

Actual Study Start Date :

Jan 5, 2022

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Period 1 (LY3410738 Alone) Single dose of LY3410738 administered orally.	Drug: LY3410738 Oral LY3410738
Experimental: Part 1 Period 2 (LY3410738 + Itraconazole) Single dose of LY3410738 administered orally with multiple doses of itraconazole orally.	Drug: LY3410738 Oral LY3410738 Drug: Itraconazole Oral Itraconazole
Experimental: Part 2 Period 1 (LY3410738 Alone) Single dose of LY3410738 administered orally.	Drug: LY3410738 Oral LY3410738
Experimental: Part 2 Period 2 (LY3410738 + Carbamazepine) Single dose of LY3410738 administered orally with multiple doses of carbamazepine orally.	Drug: LY3410738 Oral LY3410738 Drug: Carbamazepine Oral Carbamazepine

Outcome Measures

Primary Outcome Measures

Assess the impact of multiple oral doses of itraconazole on single oral dose pharmacokinetics (PK) of LY3410738 by collecting/evaluating serum at protocol-specified time points: Maximum observed plasma concentration (Cmax) [Pre-dose up to 96 hours post-dose]
PK of LY3410738
Assess the impact of multiple oral doses of itraconazole on single oral dose PK of LY3410738 by collecting/evaluating serum at protocol-specified time points: Area under the concentration-time curve from Hour 0 to last measurable concentration (AUC0-t) [Pre-dose up to 96 hours post-dose]
PK of LY3410738
Assess the impact of multiple oral doses of itraconazole on single oral dose PK of LY3410738 by collecting/evaluating serum at protocol-specified time points: Area under the concentration-time curve extrapolated to infinity (AUC0-inf) [Pre-dose up to 96 hours post-dose]
PK of LY3410738
Assess the effect of multiple oral doses of carbamazepine on single oral dose PK of LY3410738 by collecting/evaluating serum at protocol-specified time points: Cmax [Pre-dose up to 96 hours post-dose]
PK of LY3410738
Assess the effect of multiple oral doses of carbamazepine on single oral dose PK of LY3410738 by collecting/evaluating serum at protocol-specified time points: AUC0-t [Pre-dose up to 96 hours post-dose]
PK of LY3410738
Assess the effect of multiple oral doses of carbamazepine on single oral dose PK of LY3410738 by collecting/evaluating serum at protocol-specified time points: AUC0-inf [Pre-dose up to 96 hours post-dose]
PK of LY3410738

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Females of non-childbearing potential and males capable of fathering a child must use contraception
Within body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (kg/m²).
Participants will be in good health, based on medical history, physical examination findings, vital signs, 12 lead electrocardiogram (ECG), or clinical laboratory tests, as determined by the Investigator (or designee).
Able to comply with all study procedures, including the 15-night stay for those participating in part 1 or 25-night stay for those participating in part 2 at the Clinical Research Unit and follow-up phone call.

Exclusion Criteria:

History or presence of any of the following, deemed clinically significant by the

Participants with out-of-range, at-rest vital signs.
Abnormal laboratory values determined to be clinically significant by the Investigator (or designee).
Clinically significant abnormality, as determined by the Investigator (or designee), from physical examination.
Participation in any other investigational study drug trial involving administration of any investigational drug in the past 30 days or 5 half-lives, whichever was longer, prior to the first dose administration (Day 1).
Use or intention to use any prescription or over-the-counter medications within 14 days or 5 half-lives (if known) prior to the first dose administration (Day 1) and through end of trial.
History or presence of any illness or psychiatric condition, that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results, or put the participant at undue risk.
Donation of blood from 56 days prior to Screening, plasma or platelets from 4 weeks prior to Screening.
Receipt of blood products within 2 months prior to Check-in (Day -1).
Significant history of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
For Part 1 only, Having impaired hearing or a history of hearing problems
For Part 2 only, History of serious dermatological adverse reaction, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, or DRESS
For Part 2 only, Glaucoma or history of elevated intraocular pressure.
For Part 2 only, Have answered 'yes' to either Question 4 or Question 3 on the 'Suicidal Ideation' portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or have answered 'yes' to any of the suicide-related behaviors on the 'Suicidal Behavior' portion of the C-SSRS
For Part 2 only, Have laboratory evidence of clinically significant anemia, leukopenia, thrombocytopenia, or hepatic dysfunction; or hyponatremia
For Part 2 only, Genotyping test that is positive for either or both of the carbamazepine sensitivity conferring HLA alleles
Creatinine clearance < 90 mL/minute calculated using the C-G equation at Screening or Check-in
Known ongoing alcohol and/or drug abuse within 2 years prior to Screening, or evidence of such abuse as indicated by the laboratory assays for drugs of abuse (including cotinine and alcohol) conducted during Screening and/or at Check-in (Day- 1).
Consumption of foods or beverages containing grapefruit/grapefruit juice or Seville oranges or their juice within 7 days prior to Check-in (Day -1) and through end of treatment (EOT) or early termination (ET)
Have previously completed or withdrawn from this study or any other study investigating LY3410738, and have previously received LY3410738

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	LabCorp CRU, Inc.	Daytona Beach	Florida	United States	32117

Sponsors and Collaborators

Eli Lilly and Company
Loxo Oncology, Inc.

Investigators

Study Director: Yingying Guo, Medical Monitor

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT05205447

Other Study ID Numbers:

LOXO-IDH-21005
I9Y-OX-JDHF

First Posted:

Jan 25, 2022

Last Update Posted:

Jun 24, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Itraconazole

Carbamazepine

Study Results

No Results Posted as of Jun 24, 2022