Trial Outcomes & Findings for A Study to Evaluate the Effect of Pirtobrutinib (LOXO-305) on QTc Interval in Healthy Participants (NCT NCT06215521)
NCT ID: NCT06215521
Last Updated: 2025-02-24
Results Overview
The cardiodynamic assessment was performed through 12-lead electrocardiogram (ECG) extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Placebo-corrected change from baseline in QTcF (ΔΔQTcF) was calculated based on model-predicted effect.
COMPLETED
PHASE1
31 participants
Baseline (Predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
2025-02-24
Participant Flow
A total of 31 participants were enrolled in this study. Participants were randomly assigned to 1 of 6 treatment sequences (ABC, BCA, CAB, ACB, CBA and BAC) where Treatment A was single oral dose of 900 milligrams (mg) pirtobrutinib, Treatment B was single oral dose of 900 mg pirtobrutinib matched placebo and Treatment C was single oral dose of 400 mg moxifloxacin.
Participant milestones
| Measure |
Treatment Sequence 1: ABC
Participants received a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 12 and a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 23, under fasted conditions.
|
Treatment Sequence 2: BCA
Participants received a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 1, followed by a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 12 and a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 23, under fasted conditions.
|
Treatment Sequence 3: CAB
Participants received a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 12 and a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 23, under fasted conditions.
|
Treatment Sequence 4: ACB
Participants received a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 1, followed by a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 12 and a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 23, under fasted conditions.
|
Treatment Sequence 5: CBA
Participants received a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 12 and a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 23, under fasted conditions.
|
Treatment Sequence 6: BAC
Participants received a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 12 and a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 23, under fasted conditions.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (Day 1)
STARTED
|
5
|
6
|
5
|
5
|
5
|
5
|
|
Treatment Period 1 (Day 1)
Received 1 Dose of Treatment A
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Treatment Period 1 (Day 1)
Received 1 Dose of Treatment B
|
5
|
6
|
5
|
5
|
5
|
5
|
|
Treatment Period 1 (Day 1)
Received 1 Dose of Treatment C
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Treatment Period 1 (Day 1)
COMPLETED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Treatment Period 1 (Day 1)
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Treatment Period 2 (Day 12)
STARTED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Treatment Period 2 (Day 12)
COMPLETED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Treatment Period 2 (Day 12)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (Day 23)
STARTED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Treatment Period 3 (Day 23)
COMPLETED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Treatment Period 3 (Day 23)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence 1: ABC
Participants received a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 12 and a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 23, under fasted conditions.
|
Treatment Sequence 2: BCA
Participants received a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 1, followed by a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 12 and a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 23, under fasted conditions.
|
Treatment Sequence 3: CAB
Participants received a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 12 and a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 23, under fasted conditions.
|
Treatment Sequence 4: ACB
Participants received a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 1, followed by a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 12 and a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 23, under fasted conditions.
|
Treatment Sequence 5: CBA
Participants received a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 12 and a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 23, under fasted conditions.
|
Treatment Sequence 6: BAC
Participants received a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 12 and a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 23, under fasted conditions.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (Day 1)
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study to Evaluate the Effect of Pirtobrutinib (LOXO-305) on QTc Interval in Healthy Participants
Baseline characteristics by cohort
| Measure |
Treatment Sequence: ABC
n=5 Participants
Participants received a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 12 and a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 23, under fasted conditions
|
Treatment Sequence: BCA
n=6 Participants
Participants received a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 1, followed by a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 12 and a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 23, under fasted conditions.
|
Treatment Sequence: CAB
n=5 Participants
Participants received a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 12 and a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 23, under fasted conditions.
|
Treatment Sequence: ACB
n=5 Participants
Participants received a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 1, followed by a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 12 and a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 23, under fasted conditions.
|
Treatment Sequence: CBA
n=5 Participants
Participants received a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 12 and a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 23, under fasted conditions.
|
Treatment Sequence: BAC
n=5 Participants
Participants received a single oral dose of 900 mg pirtobrutinib matched placebo (Treatment B) on Day 1, followed by a single oral dose of 900 mg pirtobrutinib (Treatment A) on Day 12 and a single oral dose of 400 mg moxifloxacin (Treatment C) on Day 23, under fasted conditions.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
35.0 years
STANDARD_DEVIATION 9.87 • n=5 Participants
|
39.0 years
STANDARD_DEVIATION 8.81 • n=7 Participants
|
37.8 years
STANDARD_DEVIATION 7.95 • n=5 Participants
|
35.6 years
STANDARD_DEVIATION 7.86 • n=4 Participants
|
34.4 years
STANDARD_DEVIATION 6.77 • n=21 Participants
|
38.2 years
STANDARD_DEVIATION 10.01 • n=8 Participants
|
36.7 years
STANDARD_DEVIATION 8.08 • n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
24 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
23 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 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
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
14 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
14 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
31 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline (Predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: Pharmacokinetic/Corrected QT interval (PK/QTc) population included all participants who were in both the PK and QT/QTc populations with at least 1 pair of post-dose PK and ΔQTc data from the same time point in at least 1 period as well as participants in the QT/QTc population who received placebo. As per planned analysis, data was planned to be reported only for Treatment A (900 mg pirtobrutinib) concentration for this outcome measure.
The cardiodynamic assessment was performed through 12-lead electrocardiogram (ECG) extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Placebo-corrected change from baseline in QTcF (ΔΔQTcF) was calculated based on model-predicted effect.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF)
|
0.73 milliseconds (msec)
Interval -1.17 to 2.64
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. Here, 'Number Analyzed' signifies participants who were evaluable at specific timepoints.
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Change from baseline in (Δ) QTcF was calculated using linear mixed-effects model analysis.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
n=29 Participants
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Change From Baseline in (Δ) QTcF
Change at 6 hours post-dose
|
3.5 msec
Interval 1.48 to 5.42
|
0.9 msec
Interval -1.08 to 2.86
|
9.3 msec
Interval 7.26 to 11.26
|
|
Change From Baseline in (Δ) QTcF
Change at 0.75 hour post-dose
|
-3.8 msec
Interval -5.37 to -2.29
|
-2.0 msec
Interval -3.5 to -0.42
|
7.6 msec
Interval 6.03 to 9.17
|
|
Change From Baseline in (Δ) QTcF
Change at 1 hour post-dose
|
-2.8 msec
Interval -4.25 to -1.33
|
-1.2 msec
Interval -2.65 to 0.24
|
8.3 msec
Interval 6.88 to 9.8
|
|
Change From Baseline in (Δ) QTcF
Change at 2 hours post-dose
|
-2.2 msec
Interval -3.89 to -0.49
|
-1.1 msec
Interval -2.8 to 0.6
|
9.4 msec
Interval 7.64 to 11.1
|
|
Change From Baseline in (Δ) QTcF
Change at 2.5 hours post-dose
|
-0.2 msec
Interval -1.89 to 1.46
|
0.2 msec
Interval -1.45 to 1.9
|
10.1 msec
Interval 8.39 to 11.82
|
|
Change From Baseline in (Δ) QTcF
Change at 3 hours post-dose
|
0.3 msec
Interval -1.45 to 2.13
|
0.5 msec
Interval -1.26 to 2.32
|
9.9 msec
Interval 8.11 to 11.75
|
|
Change From Baseline in (Δ) QTcF
Change at 4 hours post-dose
|
2.2 msec
Interval 0.18 to 4.19
|
0.3 msec
Interval -1.7 to 2.32
|
9.8 msec
Interval 7.78 to 11.86
|
|
Change From Baseline in (Δ) QTcF
Change at 0.25 hour post-dose
|
-0.4 msec
Interval -1.41 to 0.68
|
0.0 msec
Interval -1.01 to 1.08
|
-0.1 msec
Interval -1.15 to 0.97
|
|
Change From Baseline in (Δ) QTcF
Change at 0.5 hour post-dose
|
-4.5 msec
Interval -5.94 to -3.06
|
-2.8 msec
Interval -4.21 to -1.33
|
4.2 msec
Interval 2.72 to 5.66
|
|
Change From Baseline in (Δ) QTcF
Change at 1.5 hours post-dose
|
-0.6 msec
Interval -2.26 to 0.98
|
-1.0 msec
Interval -2.63 to 0.61
|
9.8 msec
Interval 8.15 to 11.45
|
|
Change From Baseline in (Δ) QTcF
Change at 8.5 hours post-dose
|
-5.1 msec
Interval -7.07 to -3.09
|
-5.2 msec
Interval -7.15 to -3.17
|
2.8 msec
Interval 0.8 to 4.85
|
|
Change From Baseline in (Δ) QTcF
Change at 12 hours post-dose
|
1.2 msec
Interval -1.41 to 3.75
|
0.6 msec
Interval -1.99 to 3.17
|
6.8 msec
Interval 4.12 to 9.44
|
|
Change From Baseline in (Δ) QTcF
Change at 24 hours post-dose
|
0.0 msec
Interval -1.71 to 1.69
|
0.6 msec
Interval -1.11 to 2.41
|
5.0 msec
Interval 3.22 to 6.74
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. Here, 'Number Analyzed' signifies participants who were evaluable at specific timepoints. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
Heart rate is the number of times the ventricles of the heart contract and relax per minute. Change from baseline in heart rate (ΔHR) was calculated using linear mixed-effects model analysis.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 2 hours post-dose
|
0.5 beats per minute (beats/min)
Interval -0.73 to 1.76
|
-0.8 beats per minute (beats/min)
Interval -1.98 to 0.42
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 2.5 hours post-dose
|
2.2 beats per minute (beats/min)
Interval 0.87 to 3.54
|
-0.1 beats per minute (beats/min)
Interval -1.37 to 1.22
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 4 hours post-dose
|
1.4 beats per minute (beats/min)
Interval 0.12 to 2.67
|
0.4 beats per minute (beats/min)
Interval -0.85 to 1.61
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 0.25 hour post-dose
|
0.1 beats per minute (beats/min)
Interval -0.94 to 1.07
|
-0.9 beats per minute (beats/min)
Interval -1.81 to 0.09
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 0.5 hour post-dose
|
-0.5 beats per minute (beats/min)
Interval -1.66 to 0.61
|
-1.2 beats per minute (beats/min)
Interval -2.24 to -0.07
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 0.75 hour post-dose
|
0.0 beats per minute (beats/min)
Interval -1.28 to 1.23
|
-0.4 beats per minute (beats/min)
Interval -1.66 to 0.76
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 1 hour post-dose
|
1.0 beats per minute (beats/min)
Interval -0.23 to 2.32
|
-0.1 beats per minute (beats/min)
Interval -1.34 to 1.09
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 1.5 hours post-dose
|
0.9 beats per minute (beats/min)
Interval -0.28 to 2.06
|
-1.7 beats per minute (beats/min)
Interval -2.82 to -0.58
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 3 hours post-dose
|
1.3 beats per minute (beats/min)
Interval -0.01 to 2.52
|
0.4 beats per minute (beats/min)
Interval -0.84 to 1.6
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 6 hours post-dose
|
2.0 beats per minute (beats/min)
Interval 0.65 to 3.43
|
0.5 beats per minute (beats/min)
Interval -0.88 to 1.82
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 8.5 hours post-dose
|
4.0 beats per minute (beats/min)
Interval 2.42 to 5.59
|
3.4 beats per minute (beats/min)
Interval 1.89 to 5.0
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 12 hours post-dose
|
2.0 beats per minute (beats/min)
Interval 0.22 to 3.74
|
0.4 beats per minute (beats/min)
Interval -1.36 to 2.09
|
—
|
|
Change From Baseline in Heart Rate (ΔHR)
Change at 24 hours post-dose
|
1.2 beats per minute (beats/min)
Interval 0.0 to 2.48
|
0.8 beats per minute (beats/min)
Interval -0.41 to 2.04
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. Here, 'Number Analyzed' signifies participants evaluable for specific timepoints. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
Pulse rate is number of times heart beats per minute. Pulse rate measurements were performed using the same arm for each reading and measurements were taken after the participant had been resting in the supine position for at least 5 minutes. Change from baseline in pulse rate (ΔPR) was calculated using linear mixed-effects model analysis.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 6 hours post-dose
|
-4.4 beats per minute (beats/min)
Interval -6.12 to -2.73
|
-2.7 beats per minute (beats/min)
Interval -4.34 to -0.96
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 0.25 hour post-dose
|
-2.6 beats per minute (beats/min)
Interval -4.46 to -0.83
|
-0.8 beats per minute (beats/min)
Interval -2.6 to 1.02
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 24 hours post-dose
|
-4.2 beats per minute (beats/min)
Interval -6.59 to -1.75
|
-0.6 beats per minute (beats/min)
Interval -3.11 to 1.9
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 12 hours post-dose
|
-4.9 beats per minute (beats/min)
Interval -7.82 to -1.88
|
-2.8 beats per minute (beats/min)
Interval -5.77 to 0.17
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 8.5 hours post-dose
|
-6.2 beats per minute (beats/min)
Interval -8.3 to -4.06
|
-5.1 beats per minute (beats/min)
Interval -7.24 to -3.0
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 0.5 hour post-dose
|
0.3 beats per minute (beats/min)
Interval -1.61 to 2.15
|
1.5 beats per minute (beats/min)
Interval -0.42 to 3.34
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 0.75 hour post-dose
|
0.3 beats per minute (beats/min)
Interval -1.41 to 1.98
|
1.0 beats per minute (beats/min)
Interval -0.72 to 2.67
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 1 hour post-dose
|
-0.1 beats per minute (beats/min)
Interval -2.24 to 2.11
|
0.7 beats per minute (beats/min)
Interval -1.48 to 2.83
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 1.5 hours post-dose
|
-0.9 beats per minute (beats/min)
Interval -2.69 to 0.81
|
-1.2 beats per minute (beats/min)
Interval -2.96 to 0.54
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 2 hours post-dose
|
-0.5 beats per minute (beats/min)
Interval -1.97 to 0.99
|
-0.5 beats per minute (beats/min)
Interval -1.94 to 1.01
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 2.5 hours post-dose
|
-3.9 beats per minute (beats/min)
Interval -5.82 to -2.02
|
-0.8 beats per minute (beats/min)
Interval -2.73 to 1.06
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 3 hours post-dose
|
-0.9 beats per minute (beats/min)
Interval -2.87 to 1.13
|
-1.3 beats per minute (beats/min)
Interval -3.3 to 0.7
|
—
|
|
Change From Baseline in Pulse Rate (ΔPR)
Change at 4 hours post-dose
|
-1.6 beats per minute (beats/min)
Interval -3.23 to 0.05
|
-2.3 beats per minute (beats/min)
Interval -3.91 to -0.64
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. Here, 'Number Analyzed' signifies participants evaluable for specific timepoints. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
QRS interval in an ECG measured the total time of ventricular depolarization. It begins with Q or R wave and ends at the end of the S wave. Change from baseline in QRS intervals (Δ QRS) was calculated using linear mixed-effects model analysis.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 2 hours post-dose
|
0.0 msec
Interval -0.29 to 0.2
|
-0.1 msec
Interval -0.33 to 0.16
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 2.5 hours post-dose
|
-0.1 msec
Interval -0.39 to 0.18
|
-0.1 msec
Interval -0.41 to 0.15
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 0.25 hour post-dose
|
0.0 msec
Interval -0.24 to 0.24
|
0.0 msec
Interval -0.26 to 0.22
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 0.5 hour post-dose
|
0.2 msec
Interval -0.03 to 0.45
|
-0.1 msec
Interval -0.37 to 0.11
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 0.75 hour post-dose
|
0.2 msec
Interval -0.01 to 0.42
|
0.0 msec
Interval -0.18 to 0.25
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 1 hour post-dose
|
0.2 msec
Interval -0.18 to 0.49
|
-0.1 msec
Interval -0.43 to 0.22
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 1.5 hours post-dose
|
-0.1 msec
Interval -0.34 to 0.17
|
-0.1 msec
Interval -0.35 to 0.15
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 3 hours post-dose
|
0.2 msec
Interval -0.06 to 0.5
|
-0.1 msec
Interval -0.38 to 0.18
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 4 hours post-dose
|
0.2 msec
Interval -0.13 to 0.44
|
0.1 msec
Interval -0.19 to 0.37
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 6 hours post-dose
|
0.7 msec
Interval 0.3 to 1.01
|
0.2 msec
Interval -0.19 to 0.52
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 8.5 hours post-dose
|
-0.6 msec
Interval -1.17 to -0.12
|
0.1 msec
Interval -0.42 to 0.63
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 12 hours post-dose
|
0.4 msec
Interval -0.11 to 0.83
|
0.3 msec
Interval -0.16 to 0.78
|
—
|
|
Change From Baseline in QRS Intervals (Δ QRS)
Change at 24 hours post-dose
|
0.2 msec
Interval -0.81 to 1.23
|
-1.0 msec
Interval -2.03 to 0.1
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcS.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Change From Baseline in Individualized Heart Rate-Corrected QT Interval (ΔQTcS), If a Substantial Heart Rate Effect Was Observed
|
NA msec
Pirtobrutinib did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcS with hysteresis adjustment) could not be calculated.
|
NA msec
Pirtobrutinib Matched Placebo did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcS with hysteresis adjustment) could not be calculated.
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcI.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Change From Baseline in Optimized Heart Rate-Corrected QT Interval (ΔQTcI), If a Substantial Heart Rate Effect Was Observed
|
NA msec
Pirtobrutinib did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcI with hysteresis adjustment) could not be calculated.
|
NA msec
Pirtobrutinib matched placebo did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcI with hysteresis adjustment) could not be calculated.
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. As per planned analysis, data was planned to be reported only for Treatment A and C for this outcome measure.
Heart rate is the number of times the ventricles of the heart contract and relax per minute. Placebo-corrected change from baseline in heart rate (ΔΔHR) was calculated using linear mixed-effects model analysis.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=29 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 0.25 hours post-dose
|
0.9 beats/min
Interval -0.11 to 1.96
|
0.1 beats/min
Interval -0.92 to 1.15
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 0.5 hours post-dose
|
0.6 beats/min
Interval -0.65 to 1.9
|
3.0 beats/min
Interval 1.71 to 4.27
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 1 hour post-dose
|
1.2 beats/min
Interval -0.33 to 2.68
|
4.2 beats/min
Interval 2.71 to 5.71
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 1.5 hours post-dose
|
2.6 beats/min
Interval 1.26 to 3.92
|
2.8 beats/min
Interval 1.43 to 4.1
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 2 hours post-dose
|
1.3 beats/min
Interval -0.18 to 2.77
|
2.5 beats/min
Interval 1.02 to 3.99
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 2.5 hours post-dose
|
2.3 beats/min
Interval 0.66 to 3.9
|
2.9 beats/min
Interval 1.25 to 4.53
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 3 hours post-dose
|
0.9 beats/min
Interval -0.63 to 2.38
|
1.1 beats/min
Interval -0.38 to 2.65
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 4 hours post-dose
|
1.0 beats/min
Interval -0.51 to 2.53
|
1.9 beats/min
Interval 0.34 to 3.4
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 6 hours post-dose
|
1.6 beats/min
Interval -0.14 to 3.28
|
2.6 beats/min
Interval 0.86 to 4.32
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 8.5 hours post-dose
|
0.6 beats/min
Interval -1.47 to 2.58
|
1.5 beats/min
Interval -0.54 to 3.54
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 12 hours post-dose
|
1.6 beats/min
Interval -0.68 to 3.91
|
4.5 beats/min
Interval 2.16 to 6.82
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 24 hours post-dose
|
0.4 beats/min
Interval -1.06 to 1.91
|
1.0 beats/min
Interval -0.47 to 2.54
|
—
|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
Change at 0.75 hours post-dose
|
0.4 beats/min
Interval -1.06 to 1.91
|
3.8 beats/min
Interval 2.35 to 5.34
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. As per planned analysis, data was planned to be reported only for Treatment A and C for this outcome measure.
Pulse rate is number of times heart beats per minute. Pulse rate measurements were performed using the same arm for each reading and measurements were taken after the participant had been resting in the supine position for at least 5 minutes. Placebo-corrected change from baseline in pulse rate (ΔPR) was calculated using linear mixed-effects model analysis.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=29 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 8.5 hours post-dose
|
-1.1 beats/min
Interval -3.94 to 1.82
|
-2.1 beats/min
Interval -5.0 to 0.8
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 12 hours post-dose
|
-2.1 beats/min
Interval -6.17 to 2.06
|
-3.5 beats/min
Interval -7.63 to 0.71
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 1 hours post-dose
|
-0.7 beats/min
Interval -3.69 to 2.2
|
-3.8 beats/min
Interval -6.78 to -0.88
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 1.5 hours post-dose
|
0.3 beats/min
Interval -2.05 to 2.6
|
-3.4 beats/min
Interval -5.78 to -1.09
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 2 hours post-dose
|
0.0 beats/min
Interval -1.94 to 1.89
|
-3.6 beats/min
Interval -5.54 to -1.68
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 2.5 hours post-dose
|
-3.1 beats/min
Interval -5.64 to -0.54
|
-4.6 beats/min
Interval -7.23 to -2.05
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 3 hours post-dose
|
0.4 beats/min
Interval -2.27 to 3.13
|
-4.0 beats/min
Interval -6.7 to -1.26
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 4 hours post-dose
|
0.7 beats/min
Interval -1.47 to 2.85
|
-4.2 beats/min
Interval -6.33 to -1.98
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 6 hours post-dose
|
-1.8 beats/min
Interval -4.01 to 0.47
|
-4.3 beats/min
Interval -6.53 to -2.02
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 0.25 hours post-dose
|
-1.9 beats/min
Interval -4.28 to 0.56
|
-1.2 beats/min
Interval -3.65 to 1.24
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 0.5 hours post-dose
|
-1.2 beats/min
Interval -3.72 to 1.33
|
-2.1 beats/min
Interval -4.68 to 0.42
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 0.75 hours post-dose
|
-0.7 beats/min
Interval -2.93 to 1.55
|
-2.5 beats/min
Interval -4.8 to -0.27
|
—
|
|
Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
Change at 24 hours post-dose
|
-3.6 beats/min
Interval -6.95 to -0.18
|
-0.8 beats/min
Interval -4.19 to 2.69
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. As per planned analysis, data was planned to be reported only for Treatment A and C for this outcome measure.
QRS interval in an ECG measured the total time of ventricular depolarization. It begins with Q or R wave and ends at the end of the S wave. Placebo-corrected change from baseline in QRS intervals (ΔΔQRS) was calculated using linear mixed-effects model analysis.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=29 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 0.25 hours post-dose
|
0.0 msec
Interval -0.32 to 0.36
|
-0.3 msec
Interval -0.63 to 0.06
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 0.5 hours post-dose
|
0.3 msec
Interval 0.0 to 0.68
|
0.1 msec
Interval -0.26 to 0.43
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 0.75 hours post-dose
|
0.2 msec
Interval -0.13 to 0.47
|
0.3 msec
Interval 0.03 to 0.63
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 1 hours post-dose
|
0.3 msec
Interval -0.21 to 0.73
|
0.1 msec
Interval -0.34 to 0.59
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 1.5 hours post-dose
|
0.0 msec
Interval -0.34 to 0.37
|
0.1 msec
Interval -0.22 to 0.49
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 2 hours post-dose
|
0.0 msec
Interval -0.3 to 0.39
|
0.1 msec
Interval -0.2 to 0.5
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 4 hours post-dose
|
0.1 msec
Interval -0.33 to 0.46
|
-0.3 msec
Interval -0.67 to 0.13
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 6 hours post-dose
|
0.5 msec
Interval -0.01 to 0.99
|
-0.1 msec
Interval -0.58 to 0.43
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 8.5 hours post-dose
|
-0.8 msec
Interval -1.5 to -0.01
|
-0.4 msec
Interval -1.12 to 0.38
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 12 hours post-dose
|
0.1 msec
Interval -0.62 to 0.72
|
0.0 msec
Interval -0.65 to 0.7
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 24 hours post-dose
|
1.2 msec
Interval -0.3 to 2.65
|
0.2 msec
Interval -1.25 to 1.74
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 2.5 hours post-dose
|
0.0 msec
Interval -0.37 to 0.43
|
0.1 msec
Interval -0.33 to 0.48
|
—
|
|
Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
Change at 3 hours post-dose
|
0.3 msec
Interval -0.07 to 0.72
|
-0.1 msec
Interval -0.5 to 0.29
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: PK/QTc population included all participants who were in both the PK and QT/QTc populations with at least 1 pair of post-dose PK and ΔQTc data from the same time point in at least 1 period as well as participants in the QT/QTc population who received placebo. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Placebo-corrected Change From Baseline in ΔQTcF (ΔΔQTcF), If a Substantial Heart Rate Effect Was Observed
|
NA msec
Pirtobrutinib did not cause a substantial HR effect, hence data could not be calculated.
|
NA msec
Pirtobrutinib matched placebo did not cause a substantial HR effect, hence data could not be calculated.
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants w.ho received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcS.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Placebo-corrected Change From Baseline in Individualized Heart Rate-Corrected QT Interval (ΔΔQTcS), If a Substantial Heart Rate Effect Was Observed
|
NA msec
Pirtobrutinib did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcS with hysteresis adjustment) could not be calculated.
|
NA msec
Pirtobrutinib matched placebo did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcS with hysteresis adjustment) could not be calculated.
|
—
|
SECONDARY outcome
Timeframe: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dosePopulation: QT/QTc population included all participants who received 1 dose of study drug with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcI.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=30 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Placebo-corrected Change From Baseline in Optimized Heart Rate-Corrected QT Interval (ΔΔQTcI), If a Substantial Heart Rate Effect Was Observed
|
NA msec
Pirtobrutinib did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcI with hysteresis adjustment) could not be calculated.
|
NA msec
Pirtobrutinib matched placebo did not cause a substantial HR effect, the Fridericia's formula was chosen as the HR correction method for the QT analysis and hence the other QT correction methods (QTcI with hysteresis adjustment) could not be calculated.
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Day 33Population: The safety population included all participants who received 1 dose of study drug. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. Number of participants with potentially clinically significant ECG changes were reported.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=31 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Changes
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Day 33Population: The safety population included all participants who received 1 dose of study drug. As per planned analysis, data was planned to be reported only for Treatment A and B for this outcome measure.
The cardiodynamic assessment was performed through 12-lead ECG extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. Number of participants with treatment emergent changes in T-wave morphology and U-wave presence were reported.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=31 Participants
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Changes in T-wave Morphology and U-wave Presence
Treatment Emergent Changes in T-wave Morphology
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Treatment Emergent Changes in T-wave Morphology and U-wave Presence
Treatment Emergent Changes in U-wave Presence
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: %AUCextrap was defined as percentage extrapolation for AUC0-inf.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
Pharmacokinetic (PK): Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Pirtobrutinib
|
5.41 percentage of AUC
Geometric Coefficient of Variation 42.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: MRT was calculated by the area under the first moment curve divided by the area under the concentration time curve.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Mean Residence Time (MRT) of Pirtobrutinib
|
33.6 hours
Geometric Coefficient of Variation 14.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was calculated as (CL/F)/Lambda Z. Where, CL/F is the apparent total clearance and lambda Z is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Apparent Volume of Distribution at the Terminal Phase (Vz/F) of Pirtobrutinib
|
62.1 liter
Geometric Coefficient of Variation 22.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: Tmax was defined as the time to reach maximum observed plasma concentration (Cmax) for pirtobrutinib.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
|
4.01 hours
Interval 3.0 to 24.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: t1/2 was defined as the terminal elimination phase half-life for pirtobrutinib.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib
|
23.0 hours
Geometric Coefficient of Variation 14.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: Cmax was defined as the maximum plasma concentration for pirtobrutinib.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib
|
14300 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 23.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: AUC(0-24) was defined as the area under the plasma concentration-time curve from 0 time to 24 hours post-dose.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Area Under the Concentration-time Curve, From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib
|
229000 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 17.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: AUC(0-t) was defined as the area under the plasma concentration-time curve from 0 time to last measurable point for pirtobrutinib.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
|
452000 h*ng/mL
Geometric Coefficient of Variation 20.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as (Dose/AUC(0-inf))/F. Where AUC(0-inf) is the area under the plasma concentration-time curve from zero to infinity and F is the bioavailability of the drug.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib
|
1.88 liter per hour (L/h)
Geometric Coefficient of Variation 21.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: AUC(0-inf) was defined as the area under the plasma concentration-time curve from 0 to infinity for pirtobrutinib.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Pirtobrutinib
|
480000 h*ng/mL
Geometric Coefficient of Variation 21.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dosePopulation: PK population included participants who received 1 dose of pirtobrutinib and have at least 1 quantifiable plasma concentration of pirtobrutinib and have evaluable PK data. Here, 'Overall Number of participants analyzed' signifies individual participants who were evaluable for rate constant evaluation. As per planned analysis, data was planned to be reported only for Treatment A for this outcome measure.
PK: Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase.
Outcome measures
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 Participants
Participants who received a single oral dose of 900 mg Pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
Participants who received a single oral dose of 400 mg moxifloxacin tablets.
|
|---|---|---|---|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 17
|
0.0364 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 18
|
0.0289 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 19
|
0.0309 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 20
|
0.0271 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 21
|
0.0269 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 1
|
0.0320 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 2
|
0.0270 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 3
|
0.0356 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 4
|
0.0259 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 5
|
0.0270 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 6
|
0.0330 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 7
|
0.0310 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 8
|
0.0331 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 9
|
0.0353 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 10
|
0.0322 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 11
|
0.0271 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 12
|
0.0213 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 13
|
0.0337 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 14
|
0.0273 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 15
|
0.0229 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 16
|
0.0314 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 22
|
0.0422 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 23
|
0.0346 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 24
|
0.0273 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 25
|
0.0288 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 26
|
0.0306 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 27
|
0.0364 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 28
|
0.0299 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 29
|
0.0304 one per hour (1/h)
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
Participant 30
|
0.0283 one per hour (1/h)
|
—
|
—
|
Adverse Events
Treatment A: 900 mg Pirtobrutinib
Treatment B: 900 mg Pirtobrutinib Matched Placebo
Treatment C: 400 mg Moxifloxacin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: 900 mg Pirtobrutinib
n=30 participants at risk
Participants who received a single oral dose of 900 mg pirtobrutinib capsules.
|
Treatment B: 900 mg Pirtobrutinib Matched Placebo
n=31 participants at risk
Participants who received a single oral dose of 900 mg pirtobrutinib matched placebo capsules.
|
Treatment C: 400 mg Moxifloxacin
n=30 participants at risk
Participants who received a single oral dose of 400 mg Moxifloxacin tablet.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
2/30 • Number of events 2 • Baseline up to follow-up (up to Day 42)
All participants who received 1 dose of study drug.
|
0.00%
0/31 • Baseline up to follow-up (up to Day 42)
All participants who received 1 dose of study drug.
|
0.00%
0/30 • Baseline up to follow-up (up to Day 42)
All participants who received 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
16.7%
5/30 • Number of events 5 • Baseline up to follow-up (up to Day 42)
All participants who received 1 dose of study drug.
|
3.2%
1/31 • Number of events 1 • Baseline up to follow-up (up to Day 42)
All participants who received 1 dose of study drug.
|
3.3%
1/30 • Number of events 1 • Baseline up to follow-up (up to Day 42)
All participants who received 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60