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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05205447
• Other study ID #: LOXO-IDH-21005
• Secondary ID: I9Y-OX-JDHF
• Status: Terminated
• Phase: Phase 1
• Start date: January 5, 2022
• Est. completion date: April 12, 2022

Study information

• Verified date: December 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: April 12, 2022
• Est. primary completion date: April 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 Investigator (or designee), and/or Sponsor:

1. Allergic disease

2. Dermatological disease

3. Renal disease

4. Liver disease

5. Pancreatitis

6. Gastrointestinal disease

7. Biliary disease

8. Metabolic disease

9. Hematological disease

10. Pulmonary disease

11. Neurological disease

12. Cancer within the past 5 years

13. Cardiovascular disease

• 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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• LY3410738
Oral LY3410738
• Itraconazole
Oral Itraconazole
• Carbamazepine
Oral Carbamazepine

Locations

Country	Name	City	State
United States	LabCorp CRU, Inc.	Daytona Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	PK of LY3410738	Pre-dose up to 96 hours post-dose
Primary	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)	PK of LY3410738	Pre-dose up to 96 hours post-dose
Primary	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)	PK of LY3410738	Pre-dose up to 96 hours post-dose
Primary	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	PK of LY3410738	Pre-dose up to 96 hours post-dose
Primary	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	PK of LY3410738	Pre-dose up to 96 hours post-dose
Primary	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	PK of LY3410738	Pre-dose up to 96 hours post-dose