A Study of Imlunestrant (LY3484356) in Female Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the effect of imlunestrant on repaglinide, omeprazole and dextromethorphan, and rosuvastatin and digoxin. The study will also investigate the effect of quinidine on imlunestrant in female healthy participants of non-childbearing potential. The safety and tolerability of imlunestrant will be investigated in female healthy participants of non-childbearing potential. The study will last approximately up to 32 days for each participant excluding the screening period.

Official Title
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The Effect of Imlunestrant on CYP2C8, CYP2C19, CYP2D6, P-gp, and BCRP Activity and the Effect of P-gp Inhibition on Imlunestrant Pharmacokinetics in Healthy Women of Non-childbearing Potential

Conditions
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Healthy

Intervention / Treatment
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* Drug: Imlunestrant
* Drug: Repaglinide
* Drug: Omeprazole
* Drug: Dextromethorphan
* Drug: Quinidine
* Drug: Rosuvastatin
* Drug: Digoxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are overtly healthy as determined by medical assessment Body mass index (BMI) within the range 18.0 to 35.0 kilograms per meter squared (kg/m²) Female participants of non childbearing potential. Exclusion Criteria: Have known allergies to imlunestrant, related compounds or any components of the formulation, repaglinide, omeprazole, dextromethorphan, quinidine, rosuvastatin, or digoxin, as appropriate, or history of significant atopy. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing Use or intend to use any prescription medications/products within 14 days prior to first dose until completion of the follow-up visit, unless deemed acceptable by the investigator (or designee), including but not limited to medications that inhibit or induce cytochrome P450 (CYP) 2C8, CYP2C19, CYP2D6, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imlunestrant + Repaglinide<br>Repaglinide administered orally alone on day 1 followed by imlunestrant administered orally in combination with repaglinide orally on day 3. | Drug: Imlunestrant<br>* Administered orally.<br>* Other names: LY3484356;Drug: Repaglinide<br>* Administered orally.<br>|
| Experimental: Imlunestrant + Omeprazole & Dextromethorphan<br>Omeprazole administered in combination with dextromethorphan orally on day 1 followed by imlunestrant administered orally in combination with omeprazole and dextromethorphan orally on day 3. | Drug: Imlunestrant<br>* Administered orally.<br>* Other names: LY3484356;Drug: Omeprazole<br>* Administered orally.<br>Drug: Dextromethorphan<br>* Administered orally.<br>|
| Experimental: Imlunestrant + Quinidine<br>Imlunestrant administered orally on day 1 followed by quinidine alone orally on day 15 to 17. On day 18, imlunestrant administered orally in combination with quinidine followed by quinidine administered orally on day 19 to 24. | Drug: Imlunestrant<br>* Administered orally.<br>* Other names: LY3484356;Drug: Quinidine<br>* Administered orally.<br>|
| Experimental: Imlunestrant + Rosuvastatin & Digoxin<br>Rosuvastatin administered in combination with digoxin administered orally on day 1 followed by imlunestrant administered orally in combination with rosuvastatin and digoxin orally on day 10. | Drug: Imlunestrant<br>* Administered orally.<br>* Other names: LY3484356;Drug: Rosuvastatin<br>* Administered orally.<br>Drug: Digoxin<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Repaglinide | PK: AUC[0-∞] of Repaglinide | Predose up to 24 hours postdose | 
| PK: Maximum Observed Concentration (Cmax) of Repaglinide | PK: Cmax of Repaglinide | Predose up to 24 hours postdose | 
| PK: AUC[0-∞] of Omeprazole | PK: AUC[0-∞] of Omeprazole | Predose up to 48 hours postdose | 
| PK: Cmax of Omeprazole | PK: Cmax of Omeprazole | Predose up to 48 hours postdose | 
| PK: AUC[0-∞] of 5-hydroxyomeprazole | PK: AUC[0-∞] of 5-hydroxyomeprazole | Predose up to 48 hours postdose | 
| PK: Cmax of 5-hydroxyomeprazole | PK: Cmax of 5-hydroxyomeprazole | Predose up to 48 hours postdose | 
| PK: AUC[0-∞] of Dextromethorphan | PK: AUC[0-∞] of Dextromethorphan | Predose up to 48 hours postdose | 
| PK: Cmax of Dextromethorphan | PK: Cmax of Dextromethorphan | Predose up to 48 hours postdose | 
| PK: AUC[0-∞] of Dextrorphan | PK: AUC[0-∞] of Dextrorphan | Predose up to 48 hours postdose | 
| PK: Cmax of Dextrorphan | PK: Cmax of Dextrorphan | Predose up to 48 hours postdose | 
| PK: AUC[0-∞] of Imlunestrant | PK: AUC[0-∞] of Imlunestrant | Predose up to 168 hours postdose | 
| PK: Cmax of Imlunestrant | PK: Cmax of Imlunestrant | Predose up to 168 hours postdose | 
| PK: AUC[0-∞] of Rosuvastatin | PK: AUC[0-∞] of Rosuvastatin | Predose up to 120 hours postdose | 
| PK: Cmax of Rosuvastatin | PK: Cmax of Rosuvastatin | Predose up to 120 hours postdose | 
| PK: AUC[0-∞] of Digoxin | PK: AUC[0-∞] of Digoxin | Predose up to 120 hours postdose | 
| PK: Cmax of Digoxin | PK: Cmax of Digoxin | Predose up to 120 hours postdose |