Trial Outcomes & Findings for A Study of the Effects of Pirtobrutinib (LOXO-305) on Repaglinide (CYP2C8 Substrate) in Healthy Participants (NCT NCT06165146)
NCT ID: NCT06165146
Last Updated: 2025-03-17
Results Overview
PK: AUC(0-t) of repaglinide was reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Results posted on
2025-03-17
Participant Flow
A total of 16 participants were enrolled in two period. In Period 1, participants received repaglinide only and in Period 2, participants received pirtobrutinib only followed by pirtobrutinib + repaglinide.
Participant milestones
| Measure |
Period 1: 0.5 mg Repaglinide
Participants received a single oral dose of 0.5 milligrams (mg) repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD
Participants received oral doses of 200 mg pirtobrutinib tablets, once daily (QD) in the morning from Day 2 to Day 11.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|---|
|
Period 1 (Day 1)
STARTED
|
16
|
0
|
0
|
|
Period 1 (Day 1)
COMPLETED
|
16
|
0
|
0
|
|
Period 1 (Day 1)
NOT COMPLETED
|
0
|
0
|
0
|
|
Washout Period (11 Days)
STARTED
|
16
|
0
|
0
|
|
Washout Period (11 Days)
COMPLETED
|
16
|
0
|
0
|
|
Washout Period (11 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Period 2 (Day 2 to 11)
STARTED
|
0
|
16
|
0
|
|
Period 2 (Day 2 to 11)
COMPLETED
|
0
|
16
|
0
|
|
Period 2 (Day 2 to 11)
NOT COMPLETED
|
0
|
0
|
0
|
|
Period 2 (Day 12)
STARTED
|
0
|
0
|
16
|
|
Period 2 (Day 12)
COMPLETED
|
0
|
0
|
16
|
|
Period 2 (Day 12)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of the Effects of Pirtobrutinib (LOXO-305) on Repaglinide (CYP2C8 Substrate) in Healthy Participants
Baseline characteristics by cohort
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
|---|---|
|
Age, Continuous
|
39.1 years
STANDARD_DEVIATION 9.20 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: AUC(0-t) of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide
|
9.59 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 36.9
|
22.2 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 56.1
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: AUC(0-inf) of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide
|
9.79 h*ng/mL
Geometric Coefficient of Variation 36.5
|
22.5 h*ng/mL
Geometric Coefficient of Variation 55.7
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: AUC-inf (%extrap) of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide
|
1.94 percentage of AUC0-inf extrapolated
Geometric Coefficient of Variation 41.8
|
1.10 percentage of AUC0-inf extrapolated
Geometric Coefficient of Variation 60.6
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: Cmax of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Maximum Observed Concentration (Cmax) of Repaglinide
|
6.88 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 59.3
|
13.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 47.4
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: Tmax of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide
|
0.625 hour
Interval 0.333 to 1.0
|
0.750 hour
Interval 0.5 to 1.0
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: Lambda Z of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 1
|
0.128 one per hour (1/h)
|
0.152 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 2
|
0.130 one per hour (1/h)
|
0.150 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 3
|
0.228 one per hour (1/h)
|
0.151 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 4
|
0.0847 one per hour (1/h)
|
0.157 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 5
|
0.0809 one per hour (1/h)
|
0.139 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 6
|
0.126 one per hour (1/h)
|
0.141 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 7
|
0.138 one per hour (1/h)
|
0.247 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 8
|
0.219 one per hour (1/h)
|
0.0995 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 9
|
0.183 one per hour (1/h)
|
0.208 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 10
|
0.197 one per hour (1/h)
|
0.218 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 11
|
0.147 one per hour (1/h)
|
0.118 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 12
|
0.139 one per hour (1/h)
|
0.174 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 13
|
0.181 one per hour (1/h)
|
0.148 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 14
|
0.105 one per hour (1/h)
|
0.170 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 15
|
0.221 one per hour (1/h)
|
0.220 one per hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
Participant 16
|
0.0966 one per hour (1/h)
|
0.325 one per hour (1/h)
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: CL/F of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Apparent Systemic Clearance (CL/F) of Repaglinide
|
51.1 Liter per hour (L/h)
Geometric Coefficient of Variation 36.5
|
22.2 Liter per hour (L/h)
Geometric Coefficient of Variation 55.7
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: t½ of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide
|
4.86 hour
Geometric Coefficient of Variation 34.6
|
4.11 hour
Geometric Coefficient of Variation 30.0
|
PRIMARY outcome
Timeframe: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: Vz/F of repaglinide was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 Participants
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Apparent Volume of Distribution (Vz/F) of Repaglinide
|
358 Liter
Geometric Coefficient of Variation 39.3
|
131 Liter
Geometric Coefficient of Variation 66.0
|
PRIMARY outcome
Timeframe: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)Population: The PK Population included all participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: AUC0-t of pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
|
184000 h*ng/mL
Geometric Coefficient of Variation 22.1
|
—
|
PRIMARY outcome
Timeframe: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)Population: The PK Population included all participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: AUCtau of pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib
|
105000 h*ng/mL
Geometric Coefficient of Variation 18.0
|
—
|
PRIMARY outcome
Timeframe: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)Population: The PK Population included all participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: Cmax of pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib
|
7220 ng/mL
Geometric Coefficient of Variation 15.0
|
—
|
PRIMARY outcome
Timeframe: Period 2: 24-hour post-dose on Day 12Population: The PK Population included all participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: Ctrough of pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib
|
3050 ng/mL
Geometric Coefficient of Variation 21.8
|
—
|
PRIMARY outcome
Timeframe: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)Population: The PK Population included all participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: Tmax of pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
|
1.00 hour
Interval 0.5 to 5.0
|
—
|
PRIMARY outcome
Timeframe: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)Population: The PK Population included all participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
PK: CL/F at steady state of pirtobrutinib was reported.
Outcome measures
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 Participants
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|
|
PK: Apparent Systemic Clearance (CL/F) at Steady State of Pirtobrutinib
|
1.91 Liter per hour (L/h)
Geometric Coefficient of Variation 18.0
|
—
|
Adverse Events
Period 1: 0.5 mg Repaglinide
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Period 2: 200 mg Pirtobrutinib QD
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Period 1: 0.5 mg Repaglinide
n=16 participants at risk
Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1.
|
Period 2: 200 mg Pirtobrutinib QD
n=16 participants at risk
Participants received oral doses of 200 mg pirtobrutinib tablets, QD in the morning from Day 2 to Day 11.
|
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
n=16 participants at risk
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
6.2%
1/16 • Number of events 1 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
6.2%
1/16 • Number of events 1 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16 • Number of events 1 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
|
General disorders
Feeling abnormal
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
6.2%
1/16 • Number of events 1 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
1/16 • Number of events 1 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
6.2%
1/16 • Number of events 1 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
6.2%
1/16 • Number of events 1 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
25.0%
4/16 • Number of events 4 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
0.00%
0/16 • Baseline up to 23 days
All participants who received at least 1 dose of study drug (repaglinide and/or pirtobrutinib).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60