Trial Outcomes & Findings for A Hepatic Impairment Study for PF-04965842. (NCT NCT03626415)
NCT ID: NCT03626415
Last Updated: 2020-05-18
Results Overview
Cmax is maximum plasma concentration. It was observed directly from data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
Results posted on
2020-05-18
Participant Flow
Participant milestones
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Hepatic Impairment Study for PF-04965842.
Baseline characteristics by cohort
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58.5 Years
STANDARD_DEVIATION 5.86 • n=93 Participants
|
57.9 Years
STANDARD_DEVIATION 4.19 • n=4 Participants
|
58.6 Years
STANDARD_DEVIATION 8.21 • n=27 Participants
|
58.3 Years
STANDARD_DEVIATION 6.03 • n=483 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
15 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
23 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
18 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohortPopulation: The pharmacokinetic concentration population was defined as all participants who received 1 dose of PF-04965842 and in whom at least 1 plasma concentration value was reported.
Cmax is maximum plasma concentration. It was observed directly from data.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for PF-04965842
|
1352 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 44
|
1276 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 41
|
1426 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 63
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohortPopulation: The pharmacokinetic parameter analysis population was defined as all participants dosed who had at least 1 of the pharmocokinetics parameters of primary interest.
AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842
|
5587 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 74
|
7449 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 29
|
8603 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 55
|
SECONDARY outcome
Timeframe: From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.Population: All participants who received PF-04965842 were included in the safety analyses.
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent adverse events (TEAEs) were those with initial onset or increasing in severity between the first dose of investigational product and up to 36 days post-dose.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842
AEs (all causalities)
|
2 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842
AEs (treatment related)
|
1 Participants
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose.Population: All participants who received PF-04965842 were included in the safety analyses.
Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
|
4 Participants
|
7 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose.Population: All participants who received PF-04965842 were included in the safety analyses.
12-Lead ECGs were collected after the participants rested quietly for at least 10 minutes in a supine position. Clinical significance of ECG recordings was determined at the investigator's discretion.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose.Population: All participants who received PF-04965842 were included in the safety analyses.
Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant following at least 5 minutes of supine rest. Clinical significance of vital signs was determined at the investigator's discretion.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842
|
0 Participants
|
0 Participants
|
0 Participants
|
POST_HOC outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohortPopulation: The pharmacokinetic parameter analysis population was defined as all participants dosed who had at least 1 of the pharmocokinetic parameters of primary interest.
Cmax,u is unbound Cmax. The active moiety is comprised of parent drug PF-04965842, active metabolites PF-06471658 and PF-07055087.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Unbound Cmax (Cmax,u) for Active Moiety
|
2390 nanomolar (nM)
Geometric Coefficient of Variation 20
|
1815 nanomolar (nM)
Geometric Coefficient of Variation 36
|
2011 nanomolar (nM)
Geometric Coefficient of Variation 41
|
POST_HOC outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohortPopulation: The analysis population was defined as all participants contributing to the summary statistics for AUCinf,u.
AUCinf,u is unbound AUCinf. The active moiety is comprised of parent drug PF-04965842, active metabolites PF-06471658 and PF-07055087.
Outcome measures
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=7 Participants
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 Participants
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Unbound AUCinf (AUCinf,u) for Active Moiety
|
12010 nanomolar*hour (nM*hr)
Geometric Coefficient of Variation 40
|
11500 nanomolar*hour (nM*hr)
Geometric Coefficient of Variation 24
|
13790 nanomolar*hour (nM*hr)
Geometric Coefficient of Variation 30
|
Adverse Events
PF-04965842 (Normal Hepatic Function Cohort)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
PF-04965842 (Mild Hepatic Impairment Cohort)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
PF-04965842 (Moderate Hepatic Impairment Cohort)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PF-04965842 (Normal Hepatic Function Cohort)
n=8 participants at risk
Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Mild Hepatic Impairment Cohort)
n=8 participants at risk
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
PF-04965842 (Moderate Hepatic Impairment Cohort)
n=8 participants at risk
Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
25.0%
2/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
1/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
25.0%
2/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
0.00%
0/8 • From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER