Study of the Effects of Itraconazole and Rifampin on LOXO-305 in Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to learn about how itraconazole and rifampin affect LOXO-305 in healthy participants. Participation could last about 8 weeks.

Official Title
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A Phase 1, Open Label, Two-part, Fixed-sequence Drug Interaction Study to Investigate the Effect of Strong CYP3A4 Inhibitor (Itraconazole) and CYP3A4 Inducer (Rifampin) on the Pharmacokinetics of LOXO 305 in Healthy Adult Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LOXO-305
* Drug: Itraconazole
* Drug: Rifampin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females of non-childbearing potential. Within body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (kg/m²). Participants will be in good general 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 19-night stay for those participating in Part 1 or 24-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: liver disease pancreatitis peptic ulcer disease intestinal malabsorption gastric reduction surgery history or presence of clinically significant 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 prior to the first dose administration (Day 1) and through end of trial. History or presence, upon clinical evaluation, of any illness 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 or clinical manifestation of any metabolic, allergic, dermatological, hepatic, biliary, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the Investigator), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Period 1 (LOXO-305 Alone)<br>LOXO-305 administered orally | Drug: LOXO-305<br>* Oral LOXO-305<br>|
| Experimental: Part 1 Period 2 (Itraconazole + LOXO-305)<br>Itraconazole + LOXO-305 co-administered orally | Drug: LOXO-305<br>* Oral LOXO-305<br>Drug: Itraconazole<br>* Oral itraconazole<br>|
| Experimental: Part 2 Period 1 (LOXO-305 Alone)<br>LOXO-305 administered orally | Drug: LOXO-305<br>* Oral LOXO-305<br>|
| Experimental: Part 2 Period 2 (Rifampin + LOXO-305)<br>Rifampin + LOXO-305 co-administered orally | Drug: LOXO-305<br>* Oral LOXO-305<br>Drug: Rifampin<br>* Oral rifampin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the impact of multiple oral doses of itraconazole on single oral dose pharmacokinetics (PK) of LOXO 305 by collecting/evaluating serum at protocol-specified time points: Maximum observed plasma concentration (Cmax) | PK of LOXO-305 | Pre-dose up to 168 hours post-dose | 
| Assess the impact of multiple oral doses of itraconazole on single oral dose PK of LOXO 305 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 LOXO-305 | Pre-dose up to 168 hours post-dose | 
| Assess the impact of multiple oral doses of itraconazole on single oral dose PK of LOXO 305 by collecting/evaluating serum at protocol-specified time points: Area under the concentration-time curve extrapolated to infinity (AUC0-inf) | PK of LOXO-305 | Pre-dose up to 168 hours post-dose | 
| Assess the effect of multiple oral doses of rifampin on single oral dose PK of LOXO 305 by collecting/evaluating serum at protocol-specified time points: Cmax | PK of LOXO-305 | Pre-dose up to 168 hours post-dose | 
| Assess the effect of multiple oral doses of rifampin on single oral dose PK of LOXO 305 by collecting/evaluating serum at protocol-specified time points: AUC0-t | PK of LOXO-305 | Pre-dose up to 168 hours post-dose | 
| Assess the effect of multiple oral doses of rifampin on single oral dose PK of LOXO 305 by collecting/evaluating serum at protocol-specified time points: AUC0-inf | PK of LOXO-305 | Pre-dose up to 168 hours post-dose | 
| Assess the effect of a single oral dose of rifampin on single oral dose PK of LOXO-305 by collecting/evaluating serum at protocol-specified time points: Cmax | PK of LOXO-305 | Pre-dose up to 168 hours post-dose | 
| Assess the effect of a single oral dose of rifampin on single oral dose PK of LOXO-305 by collecting/evaluating serum at protocol-specified time points: Area under the concentration time curve from hour 0 to 24 hours postdose (AUC0-24) | PK of LOXO-305 | Pre-dose up to 168 hours post-dose |