Healthy Volunteers
Conditions
Brief summary
The first purpose of this study is to evaluate the effect of itraconazole (and possibly diltiazem) on the amount of LY2623091 in the blood stream and how long the body takes to get rid of it. The second purpose of the study is to evaluate the effect of LY2623091 on the amount of simvastatin (and possibly tadalafil) in the blood stream and how long the body takes to get rid of it. The safety and tolerability of LY2623091 when given with itraconazole, simvastatin and diltiazem or tadalafil will be evaluated. There will be three groups of participants in this study. Results from Groups 1 and 2 will be analyzed during the study to determine whether to enroll participants in Group 3 or 4. The study is expected to last up to 40 days from the first dose to follow-up (inclusive). Screening may occur up to 28 days prior to enrollment.
Interventions
DRUGLY2623091
Administered orally
DRUGItraconazole
Administered orally
DRUGSimvastatin
Administered orally
DRUGTadalafil
Administered orally
DRUGDiltiazem
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants as determined by medical history, physical examination, clinical laboratory tests, and electrocardiograms (ECGs). * Have a body mass index (BMI) between 18 and 32.0 kilograms per square meter (kg/m\^2) inclusive, at screening * Female participants must be of non-childbearing potential
Exclusion criteria
* In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2623091 | Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of LY2623091 | Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY2623091 | Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose |
| Pharmacokinetics: Maximum Drug Concentration (Cmax) of Simvastatin and Simvastatin Acid | Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Simvastatin and Simvastatin Acid | Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of Simvastatin and Simvastatin Acid | Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose |
Countries
United States
Participant flow
Pre-assignment details
This study planned to enroll 3 groups. After Groups 1 and 2 were enrolled, data from Group 2 were analyzed according to a pre-specified algorithm. Results met criteria to enroll Group 4. (Group 3 was not enrolled.)
Participants by arm
| Arm | Count |
|---|---|
| LY2623091 + Itraconazole (Group 1) Period 1: Single oral dose of 6 mg LY2623091 on Day 1.
Period 2: Oral doses of 200 mg itraconazole BID on Day 1 and then QD on Days 2 to 20 with a single oral dose of 6 mg LY2623091 coadministered on Day 6. | 16 |
| Simvastatin + LY2623091 (Group 2) Single oral dose of 20 mg simvastatin on Day 1 followed by oral doses of 24.5 mg LY2623091 QD on Days 3 to 13, with a single oral dose of 20 mg simvastatin coadministered on Day 12. | 16 |
| LY2623091 + Diltiazem (Group 4) Period 1: Single oral dose of 6 mg LY2623091 on Day 1.
Period 2: Oral doses of 240 mg diltiazem extended release QD on Days 1 to 13, with a single oral dose of 6 mg LY2623091 coadministered on Day 4. | 16 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 1 |
| Period 1 | Withdrawal by Subject | 0 | 0 | 1 |
| Period 2 | Adverse Event | 1 | 0 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | LY2623091 + Itraconazole (Group 1) | LY2623091 + Diltiazem (Group 4) | Simvastatin + LY2623091 (Group 2) |
|---|---|---|---|---|
| Age, Continuous | 39.7 years STANDARD_DEVIATION 9.5 | 42.1 years STANDARD_DEVIATION 9.4 | 39.2 years STANDARD_DEVIATION 9.3 | 37.8 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 9 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 7 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 5 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 10 Participants | 10 Participants | 9 Participants |
| Region of Enrollment United States | 48 participants | 16 participants | 16 participants | 16 participants |
| Sex: Female, Male Female | 13 Participants | 4 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 35 Participants | 12 Participants | 9 Participants | 14 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 3 / 16 | 6 / 16 | 0 / 16 | 4 / 16 | 1 / 16 | 3 / 16 | 1 / 14 | 1 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY2623091
Time frame: Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose
Population: All participants in Groups 1 and 4 who received at least one dose of study drug and had evaluable AUC(0-tlast) results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY2623091 | 2480 ng*hr/mL | Geometric Coefficient of Variation 27 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY2623091 | 5240 ng*hr/mL | Geometric Coefficient of Variation 31 |
| LY2623091 (Group 4) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY2623091 | 2340 ng*hr/mL | Geometric Coefficient of Variation 39 |
| Diltiazem + LY2623091 (Group 4) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY2623091 | 3130 ng*hr/mL | Geometric Coefficient of Variation 40 |
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of Simvastatin and Simvastatin Acid
Time frame: Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Population: All participants in Group 2 who received at least one dose of study drug and had evaluable AUC(0-tlast) results.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of Simvastatin and Simvastatin Acid | Simvastatin | 16.5 ng*hr/mL | Geometric Coefficient of Variation 49 |
| LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 5.42 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of Simvastatin and Simvastatin Acid | Simvastatin | 23.0 ng*hr/mL | Geometric Coefficient of Variation 34 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 6.87 ng*hr/mL | Geometric Coefficient of Variation 87 |
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of LY2623091
Time frame: Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose
Population: All participants in Groups 1 and 4 who received at least one dose of study drug and had evaluable AUC(0-infinity) results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of LY2623091 | 2540 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 27 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of LY2623091 | 5660 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 31 |
| LY2623091 (Group 4) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of LY2623091 | 2390 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39 |
| Diltiazem + LY2623091 (Group 4) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of LY2623091 | 3360 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Simvastatin and Simvastatin Acid
Time frame: Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Population: All participants in Group 2 who received at least one dose of study drug and had evaluable AUC(0-infinity) results.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Simvastatin and Simvastatin Acid | Simvastatin | 17.4 ng*h/mL | Geometric Coefficient of Variation 48 |
| LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 7.15 ng*h/mL | Geometric Coefficient of Variation 56 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Simvastatin and Simvastatin Acid | Simvastatin | 24.1 ng*h/mL | Geometric Coefficient of Variation 34 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 8.88 ng*h/mL | Geometric Coefficient of Variation 77 |
Primary
Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2623091
Time frame: Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose
Population: All participants in Groups 1 and 4 who received at least one dose of study drug and had evaluable Cmax results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2623091 (Group 1) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2623091 | 61.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2623091 | 66.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| LY2623091 (Group 4) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2623091 | 61.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| Diltiazem + LY2623091 (Group 4) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2623091 | 64.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30 |
Primary
Pharmacokinetics: Maximum Drug Concentration (Cmax) of Simvastatin and Simvastatin Acid
Time frame: Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Population: All participants in Group 2 who received at least one dose of study drug and had evaluable Cmax results.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2623091 (Group 1) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin | 7.78 ng/mL | Geometric Coefficient of Variation 63 |
| LY2623091 (Group 1) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 0.720 ng/mL | Geometric Coefficient of Variation 41 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin | 9.89 ng/mL | Geometric Coefficient of Variation 45 |
| Itraconazole + LY2623091 (Group 1) | Pharmacokinetics: Maximum Drug Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 0.877 ng/mL | Geometric Coefficient of Variation 55 |