Healthy Volunteers
Conditions
Brief summary
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.
Interventions
Sponsors
Loxo Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 | Cmax of LOXO-305 |
| Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 | PK: AUC0-t of LOXO 305 |
| Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 | AUC0-inf of LOXO-305 |
| Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8 | Cmax of LOXO-305 |
| Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8 | PK: AUC0-t of LOXO 305 |
| Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17 | AUC0-inf of LOXO-305 |
| Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on days 1 and 8 | AUC0-24 of LOXO-305 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (LOXO-305/Itraconazole) * Day 1: a single oral dose of 200 milligrams (mg) LOXO-305 was administered.
* Day 8: oral doses of 200 mg itraconazole was administered twice daily.
* Days 9 to 18: single oral dose of 200 mg itraconazole was administered once daily, and on Day 12 it was co-administered with a single oral dose of 200 mg LOXO-305. | 15 |
| Part 2 (LOXO 305/Rifampin) * Day 1: a single oral dose of 200 mg LOXO-305 was administered
* Days 8 to 23: oral dose of 600 mg rifampin was administered once daily, and on Days 8 & 17, it was co-administered with a single oral dose of 200 mg LOXO-305. | 12 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Subject Discontinued Out of Precaution Due to Covid-19 | 3 | 0 |
Baseline characteristics
| Characteristic | Part 1 (LOXO-305/Itraconazole) | Total | Part 2 (LOXO 305/Rifampin) |
|---|---|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 9.13 | 39.2 years STANDARD_DEVIATION 8.54 | 40.9 years STANDARD_DEVIATION 7.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 21 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 20 Participants | 11 Participants |
| Region of Enrollment United States | 15 Participants | 27 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 22 Participants | 10 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 15 | 2 / 12 | 1 / 12 | 0 / 12 | 0 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 15 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305
Cmax of LOXO-305
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12
Population: All part 1 participants who received a dose of LOXO-305 on day 1, itraconazole with LOXO-305 on day 12, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Day 1 | 4000 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23.5 |
| Part 1 (LOXO-305/Itraconazole) | Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Day 12 | 4100 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17.2 |
Primary
Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305
AUC0-inf of LOXO-305
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12
Population: All part 1 participants who received a dose of LOXO-305 on day 1, itraconazole with LOXO-305 on day 12, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | Day 1 | 80800 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.4 |
| Part 1 (LOXO-305/Itraconazole) | Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | Day 12 | 123000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.4 |
Primary
Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305
PK: AUC0-t of LOXO 305
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12
Population: All part 1 participants who received a dose of LOXO-305 on day 1, itraconazole with LOXO-305 on day 12, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | Day 12 | 122000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 22.7 |
| Part 1 (LOXO-305/Itraconazole) | Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | Day 1 | 80000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.4 |
Primary
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305
AUC0-24 of LOXO-305
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on days 1 and 8
Population: All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 8, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305 | Day 1 | 50200 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 14.5 |
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305 | Day 8 | 48600 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 14.7 |
Primary
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305
AUC0-inf of LOXO-305
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17
Population: All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 17, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | Day 1 | 80600 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 17.3 |
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | Day 17 | 23600 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.8 |
Primary
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305
PK: AUC0-t of LOXO 305
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8
Population: All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 8 and day 17, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | Day 1 | 79700 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 17.6 |
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | Day 8 | 48500 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 14.7 |
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | Day 17 | 23000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.1 |
Primary
Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305
Cmax of LOXO-305
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8
Population: All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 8 and day 17, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Day 1 | 4480 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 20.4 |
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Day 8 | 4170 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15.6 |
| Part 1 (LOXO-305/Itraconazole) | Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Day 17 | 2580 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22.4 |