Trial Outcomes & Findings for A Study of Two Different Formulations of Pirtobrutinib (LOXO-305) In Healthy Participants (NCT NCT06258174)
NCT ID: NCT06258174
Last Updated: 2025-01-13
Results Overview
PK: AUC0-24 of Pirtobrutinib
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
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
Results posted on
2025-01-13
Participant Flow
Participants were randomized to 2 treatment sequences (R/T, T/R), with each sequence having 2 periods where participants were crossed over between the periods. A washout period of 7 days was maintained between doses of each treatment period.
Participant milestones
| Measure |
200 mg Pirtobrutinib (Sequence R/T)
Period 1: Participants received a reference formulation (R) of oral pirtobrutinib 200 milligrams (mg) on day 1.
Period 2: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 8.
There was a washout period of 7 days between the doses of pirtobrutinib.
|
200 mg Pirtobrutinib (Sequence T/R)
Period 1: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 1.
Period 2: Participants received a reference formulation (R) of oral pirtobrutinib 200 mg on day 8.
There was a washout period of 7 days between the doses of pirtobrutinib.
|
|---|---|---|
|
Period 1
STARTED
|
14
|
14
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
14
|
14
|
|
Period 1
COMPLETED
|
14
|
14
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
14
|
14
|
|
Period 2
Received at Least 1 Dose of Study Drug
|
14
|
14
|
|
Period 2
COMPLETED
|
14
|
14
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Two Different Formulations of Pirtobrutinib (LOXO-305) In Healthy Participants
Baseline characteristics by cohort
| Measure |
200 mg Pirtobrutinib (Sequence R/T)
n=14 Participants
Period 1: Participants received a reference formulation (R) of oral pirtobrutinib 200 mg on day 1.
Period 2: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 8.
There was a washout period of 7 days between the doses of pirtobrutinib.
|
200 mg Pirtobrutinib (Sequence T/R)
n=14 Participants
Period 1: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 1.
Period 2: Participants received a reference formulation (R) of oral pirtobrutinib 200 mg on day 8.
There was a washout period of 7 days between the doses of pirtobrutinib.
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.2 years
STANDARD_DEVIATION 6.860 • n=5 Participants
|
33.5 years
STANDARD_DEVIATION 9.940 • n=7 Participants
|
36.9 years
STANDARD_DEVIATION 9.050 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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: AUC0-24 of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib
|
48800 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 29.1
|
49700 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 20.6
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
|
81100 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 36
|
83600 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 24.7
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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-inf of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib
|
82000 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 35.5
|
84700 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 24.4
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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: %AUCextrap of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib
|
1.01 percentage of AUCextrap
Geometric Coefficient of Variation 46.9
|
1.12 percentage of AUCextrap
Geometric Coefficient of Variation 36.7
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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 of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib
|
2.44 liter per hour (L/h)
Geometric Coefficient of Variation 35.5
|
2.36 liter per hour (L/h)
Geometric Coefficient of Variation 24.4
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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: t1/2 of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib
|
18.9 hours
Geometric Coefficient of Variation 21.2
|
19 hours
Geometric Coefficient of Variation 20.3
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib
|
3960 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 23.3
|
3980 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 24.2
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: 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
PK: Tmax of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
|
2.50 hours
Interval 0.5 to 6.0
|
2.50 hours
Interval 0.75 to 6.0
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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: λZ of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 1
|
0.0487 1/hour (1/h)
|
0.0347 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 2
|
0.0420 1/hour (1/h)
|
0.0374 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 3
|
0.0549 1/hour (1/h)
|
0.0563 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 4
|
0.0446 1/hour (1/h)
|
0.0386 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 5
|
0.0406 1/hour (1/h)
|
0.0382 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 6
|
0.0382 1/hour (1/h)
|
0.0389 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 7
|
0.0355 1/hour (1/h)
|
0.0348 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 8
|
0.0335 1/hour (1/h)
|
0.0341 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 9
|
0.0414 1/hour (1/h)
|
0.0390 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 10
|
0.0431 1/hour (1/h)
|
0.0437 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 11
|
0.0358 1/hour (1/h)
|
0.0321 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 12
|
0.0432 1/hour (1/h)
|
0.0427 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 13
|
0.0324 1/hour (1/h)
|
0.0382 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 14
|
0.0198 1/hour (1/h)
|
0.0179 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 15
|
0.0409 1/hour (1/h)
|
0.0371 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 16
|
0.0457 1/hour (1/h)
|
0.0451 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 17
|
0.0279 1/hour (1/h)
|
0.0284 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 18
|
0.0305 1/hour (1/h)
|
0.0299 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 19
|
0.0407 1/hour (1/h)
|
0.0478 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 20
|
0.0290 1/hour (1/h)
|
0.0350 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 21
|
0.0293 1/hour (1/h)
|
0.0342 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 22
|
0.0408 1/hour (1/h)
|
0.0403 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 23
|
0.0340 1/hour (1/h)
|
0.0322 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 24
|
0.0269 1/hour (1/h)
|
0.0299 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 25
|
0.0372 1/hour (1/h)
|
0.0379 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 26
|
0.0359 1/hour (1/h)
|
0.0396 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 27
|
0.0370 1/hour (1/h)
|
0.0369 1/hour (1/h)
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Subject 28
|
0.0360 1/hour (1/h)
|
0.0368 1/hour (1/h)
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: All randomized 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: Vz/F of Pirtobrutinib
Outcome measures
| Measure |
200 mg Pirtobrutinib (Reference Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 Participants
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib
|
66.6 Liter (L)
Geometric Coefficient of Variation 36.7
|
64.9 Liter (L)
Geometric Coefficient of Variation 28.4
|
Adverse Events
200 mg Pirtobrutinib (Reference Formulation)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
200 mg Pirtobrutinib (Test Formulation)
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 |
200 mg Pirtobrutinib (Reference Formulation)
n=28 participants at risk
Participants from R/T and T/R randomized sequences who received reference formulation (R) of oral pirtobrutinib 200 mg.
|
200 mg Pirtobrutinib (Test Formulation)
n=28 participants at risk
Participants from R/T and T/R randomized sequences who received test formulation (T) of oral pirtobrutinib 200 mg.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/28 • Baseline to Follow-up (Up To Day 24)
All randomized participants who received at least one dose of study drug.
|
3.6%
1/28 • Baseline to Follow-up (Up To Day 24)
All randomized participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60