Healthy
Conditions
Brief summary
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.
Interventions
DRUGImlunestrant
Administered orally.
DRUGRepaglinide
Administered orally.
DRUGOmeprazole
Administered orally.
DRUGDextromethorphan
Administered orally.
DRUGQuinidine
Administered orally.
DRUGRosuvastatin
Administered orally.
DRUGDigoxin
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK: Cmax of Omeprazole (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | PK: Cmax of Omeprazole |
| PK: AUC[0-∞] of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | 5-hydroxyomeprazole is a major metabolite of omeprazole. |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Repaglinide (Cohort 1) | Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose | PK: AUC\[0-∞\] of Repaglinide |
| PK: Maximum Observed Concentration (Cmax) of Repaglinide (Cohort 1) | Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose | PK: Cmax of Repaglinide |
| PK: AUC[0-∞] of Omeprazole (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | PK: AUC\[0-∞\] of Omeprazole |
| PK: Cmax of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | 5-hydroxyomeprazole is a major metabolite of omeprazole. |
| PK: AUC[0-∞] of Dextromethorphan (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | PK: AUC\[0-∞\] of Dextromethorphan |
| PK: Cmax of Dextromethorphan (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | PK: Cmax of Dextromethorphan |
| PK: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUC[0-tlast]) of Dextromethorphan Metabolite: Dextrorphan (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | Dextrorphan is a major metabolite of Dextromethorphan. |
| PK: Cmax of Dextromethorphan Metabolite: Dextrorphan (Cohort 2) | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose | Dextrorphan is a major metabolite of Dextromethorphan. |
| PK: AUC[0-∞] of Imlunestrant (Cohort 3) | Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose | PK: AUC\[0-∞\] of Imlunestrant |
| PK: Cmax of Imlunestrant (Cohort 3) | Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose | PK: Cmax of Imlunestrant |
| PK: AUC[0-∞] of Rosuvastatin (Cohort 4) | Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose | PK: AUC\[0-∞\] of Rosuvastatin |
| PK: Cmax of Rosuvastatin (Cohort 4) | Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose | PK: Cmax of Rosuvastatin |
| PK: AUC[0-∞] of Digoxin (Cohort 4) | Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose | PK: AUC\[0-∞\] of Digoxin |
| PK: Cmax of Digoxin (Cohort 4) | Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose | PK: Cmax of Digoxin |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imlunestrant + Repaglinide (Cohort 1) Participants received:
Day 1: A single oral dose of 0.5 mg repaglinide administered alone.
Day 3: A single oral dose of 800 mg imlunestrant, followed approximately 2 hours later by 0.5 mg repaglinide, both administered orally. | 27 |
| Imlunestrant + Omeprazole & Dextromethorphan (Cohort 2) Participants received:
Day 1: A single oral dose of 20 mg omeprazole and 30 mg dextromethorphan, administered in the morning.
Day 3: A single oral dose of 800 mg imlunestrant, followed immediately by 20 mg omeprazole and 30 mg dextromethorphan, all administered orally. | 27 |
| Imlunestrant + Quinidine (Cohort 3) Participants received:
Day 1: A single oral dose of 400 mg imlunestrant, administered in the morning.
Days 15 to 17 and 19 to 24: Twice-daily oral doses of 200 mg quinidine, administered alone.
Day 18: A single oral dose of 400 mg imlunestrant administered in combination with 200 mg quinidine (quinidine was dosed twice on this day as part of the regular regimen). | 32 |
| Imlunestrant + Rosuvastatin & Digoxin (Cohort 4) Participants received:
Day 1: A single oral dose of 10 mg rosuvastatin and 0.25 mg digoxin, administered in the morning.
Day 10: A single oral dose of 400 mg imlunestrant, administered in combination with 10 mg rosuvastatin and 0.25 mg digoxin, all administered orally. | 27 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Imlunestrant + Repaglinide (Cohort 1) | Imlunestrant + Omeprazole & Dextromethorphan (Cohort 2) | Imlunestrant + Quinidine (Cohort 3) | Imlunestrant + Rosuvastatin & Digoxin (Cohort 4) |
|---|---|---|---|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 7.4 | 53.3 years STANDARD_DEVIATION 8.2 | 52.6 years STANDARD_DEVIATION 8.2 | 55.9 years STANDARD_DEVIATION 6.3 | 54.1 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 78 Participants | 22 Participants | 19 Participants | 23 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 5 Participants | 8 Participants | 9 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 3 Participants | 5 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 23 Participants | 21 Participants | 27 Participants | 19 Participants |
| Region of Enrollment United States | 113 Participants | 27 Participants | 27 Participants | 32 Participants | 27 Participants |
| Sex: Female, Male Female | 113 Participants | 27 Participants | 27 Participants | 32 Participants | 27 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 32 | 0 / 32 | 0 / 31 | 0 / 31 | 0 / 27 | 0 / 26 |
| other Total, other adverse events | 2 / 27 | 0 / 27 | 3 / 27 | 3 / 27 | 9 / 32 | 3 / 32 | 0 / 31 | 4 / 31 | 0 / 27 | 1 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 32 | 0 / 32 | 0 / 31 | 0 / 31 | 0 / 27 | 0 / 26 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Repaglinide (Cohort 1)
PK: AUC\[0-∞\] of Repaglinide
Time frame: Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose
Population: All participants in Cohort 1 who received at least one dose of repaglinide and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Repaglinide (Cohort 1) | 13.0 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Repaglinide (Cohort 1) | 13.6 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
Primary
PK: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUC[0-tlast]) of Dextromethorphan Metabolite: Dextrorphan (Cohort 2)
Dextrorphan is a major metabolite of Dextromethorphan.
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All Cohort 2 participants who received at least one dose of dextromethorphan and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUC[0-tlast]) of Dextromethorphan Metabolite: Dextrorphan (Cohort 2) | 11.8 ng*hr/mL | Geometric Coefficient of Variation 62 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUC[0-tlast]) of Dextromethorphan Metabolite: Dextrorphan (Cohort 2) | 11.9 ng*hr/mL | Geometric Coefficient of Variation 75 |
Primary
PK: AUC[0-∞] of Dextromethorphan (Cohort 2)
PK: AUC\[0-∞\] of Dextromethorphan
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All Cohort 2 participants who received at least one dose of dextromethorphan and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: AUC[0-∞] of Dextromethorphan (Cohort 2) | 14.7 ng*hr/mL | Geometric Coefficient of Variation 127 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: AUC[0-∞] of Dextromethorphan (Cohort 2) | 16.1 ng*hr/mL | Geometric Coefficient of Variation 111 |
Primary
PK: AUC[0-∞] of Digoxin (Cohort 4)
PK: AUC\[0-∞\] of Digoxin
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
Population: All cohort 4 participants who received at least one dose of digoxin and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: AUC[0-∞] of Digoxin (Cohort 4) | 20.2 ng*hr/mL | Geometric Coefficient of Variation 23 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: AUC[0-∞] of Digoxin (Cohort 4) | 28.0 ng*hr/mL | Geometric Coefficient of Variation 19 |
Primary
PK: AUC[0-∞] of Imlunestrant (Cohort 3)
PK: AUC\[0-∞\] of Imlunestrant
Time frame: Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose
Population: All cohort 3 participants who received at least one dose of imlunestrant and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: AUC[0-∞] of Imlunestrant (Cohort 3) | 1970 ng*hr/mL | Geometric Coefficient of Variation 66 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: AUC[0-∞] of Imlunestrant (Cohort 3) | 1870 ng*hr/mL | Geometric Coefficient of Variation 87 |
Primary
PK: AUC[0-∞] of Omeprazole (Cohort 2)
PK: AUC\[0-∞\] of Omeprazole
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All participants in Cohort 2, who received at least one dose of omeprazole and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: AUC[0-∞] of Omeprazole (Cohort 2) | 703 ng*hr/mL | Geometric Coefficient of Variation 77 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: AUC[0-∞] of Omeprazole (Cohort 2) | 825 ng*hr/mL | Geometric Coefficient of Variation 74 |
Primary
PK: AUC[0-∞] of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2)
5-hydroxyomeprazole is a major metabolite of omeprazole.
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All participants in Cohort 2, who received at least one dose of omeprazole and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: AUC[0-∞] of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2) | 571 ng*hr/mL | Geometric Coefficient of Variation 26 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: AUC[0-∞] of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2) | 592 ng*hr/mL | Geometric Coefficient of Variation 19 |
Primary
PK: AUC[0-∞] of Rosuvastatin (Cohort 4)
PK: AUC\[0-∞\] of Rosuvastatin
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
Population: All cohort 4 participants who received at least one dose of rosuvastatin and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: AUC[0-∞] of Rosuvastatin (Cohort 4) | 29.0 ng*hr/mL | Geometric Coefficient of Variation 47 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: AUC[0-∞] of Rosuvastatin (Cohort 4) | 44.9 ng*hr/mL | Geometric Coefficient of Variation 51 |
Primary
PK: Cmax of Dextromethorphan (Cohort 2)
PK: Cmax of Dextromethorphan
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All Cohort 2 participants who received at least one dose of dextromethorphan and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Cmax of Dextromethorphan (Cohort 2) | 0.864 ng/mL | Geometric Coefficient of Variation 124 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Cmax of Dextromethorphan (Cohort 2) | 1.13 ng/mL | Geometric Coefficient of Variation 124 |
Primary
PK: Cmax of Dextromethorphan Metabolite: Dextrorphan (Cohort 2)
Dextrorphan is a major metabolite of Dextromethorphan.
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All Cohort 2 participants who received at least one dose of dextromethorphan and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Cmax of Dextromethorphan Metabolite: Dextrorphan (Cohort 2) | 1.79 ng/mL | Geometric Coefficient of Variation 50 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Cmax of Dextromethorphan Metabolite: Dextrorphan (Cohort 2) | 1.97 ng/mL | Geometric Coefficient of Variation 56 |
Primary
PK: Cmax of Digoxin (Cohort 4)
PK: Cmax of Digoxin
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
Population: All cohort 4 participants who received at least one dose of digoxin and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Cmax of Digoxin (Cohort 4) | 1.17 ng/mL | Geometric Coefficient of Variation 39 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Cmax of Digoxin (Cohort 4) | 1.88 ng/mL | Geometric Coefficient of Variation 38 |
Primary
PK: Cmax of Imlunestrant (Cohort 3)
PK: Cmax of Imlunestrant
Time frame: Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose
Population: All cohort 3 participants who received at least one dose of imlunestrant and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Cmax of Imlunestrant (Cohort 3) | 61.0 ng/mL | Geometric Coefficient of Variation 82 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Cmax of Imlunestrant (Cohort 3) | 54.3 ng/mL | Geometric Coefficient of Variation 81 |
Primary
PK: Cmax of Omeprazole (Cohort 2)
PK: Cmax of Omeprazole
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All participants in Cohort 2, who received at least one dose of omeprazole and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Cmax of Omeprazole (Cohort 2) | 316 ng/mL | Geometric Coefficient of Variation 73 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Cmax of Omeprazole (Cohort 2) | 405 ng/mL | Geometric Coefficient of Variation 57 |
Primary
PK: Cmax of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2)
5-hydroxyomeprazole is a major metabolite of omeprazole.
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Population: All participants in Cohort 2, who received at least one dose of omeprazole and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Cmax of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2) | 200 ng/mL | Geometric Coefficient of Variation 52 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Cmax of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2) | 230 ng/mL | Geometric Coefficient of Variation 42 |
Primary
PK: Cmax of Rosuvastatin (Cohort 4)
PK: Cmax of Rosuvastatin
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
Population: All cohort 4 participants who received at least one dose of rosuvastatin and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Cmax of Rosuvastatin (Cohort 4) | 2.99 ng/mL | Geometric Coefficient of Variation 53 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Cmax of Rosuvastatin (Cohort 4) | 5.08 ng/mL | Geometric Coefficient of Variation 59 |
Primary
PK: Maximum Observed Concentration (Cmax) of Repaglinide (Cohort 1)
PK: Cmax of Repaglinide
Time frame: Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose
Population: All participants in Cohort 1 who received at least one dose of repaglinide and had evaluable PK data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg Repaglinide | PK: Maximum Observed Concentration (Cmax) of Repaglinide (Cohort 1) | 10.5 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 38 |
| 800 mg Imlunestrant + 0.5 mg Repaglinide | PK: Maximum Observed Concentration (Cmax) of Repaglinide (Cohort 1) | 9.84 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 44 |