Trial Outcomes & Findings for A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers (NCT NCT04016077)
NCT ID: NCT04016077
Last Updated: 2021-04-08
Results Overview
AUC24 of PF-06651600 pre and post dose.
COMPLETED
PHASE1
18 participants
Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
2021-04-08
Participant Flow
Eight participants were originally enrolled in each cohort. Two participants in moderate hepatic impairment cohort who discontinued from study treatment were included as "completed" and 2 additional participants were enrolled to ensure an adequate number of evaluable participants.
Participant milestones
| Measure |
Moderate Hepatic Impairment
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
8
|
|
Overall Study
COMPLETED
|
10
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 Participants
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.0 Years
STANDARD_DEVIATION 6.88 • n=5 Participants
|
57.4 Years
STANDARD_DEVIATION 6.48 • n=7 Participants
|
58.3 Years
STANDARD_DEVIATION 6.56 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10Population: The analysis population was defined as all participants treated who have at least 1 of the pharmacokinetic (PK) parameters of primary interest.
AUC24 of PF-06651600 pre and post dose.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 Participants
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600
|
454.5 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 45
|
383.6 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 16
|
PRIMARY outcome
Timeframe: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10Population: The analysis population was defined as all participants treated who have at least 1 of the PK parameters of primary interest.
Cmax is maximum observed plasma concentration.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 Participants
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) for PF-06651600
|
194.3 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 49
|
186.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 24
|
SECONDARY outcome
Timeframe: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)Population: All participants assigned to investigational product and who took at least 1 dose of investigational product.
AEs with all causalities were any untoward medical occurrences in a study participant administered a product which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 Participants
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
AEs (all causalities)
|
4 Participants
|
2 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
AEs (treatment related)
|
4 Participants
|
1 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
SAEs (all causalities)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
SAEs (treatment related)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)Population: All participants assigned to investigational product and who took at least 1 dose of investigational product.
Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, prothrombin time, prothrombin intl. normalized ratio), chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, sodium, potassium, calcium, bicarbonate and glucose), urinalysis (glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin and nitrite). Each parameter was evaluated against commonly used and widely accepted criteria.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 Participants
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
|
9 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)Population: All participants assigned to investigational product and who took at least 1 dose of investigational product.
Vital signs included supine blood pressure, pulse rate and temperature. The pre-specified out of range criterion for supine diastolic blood pressure was change from baseline equal to or over than (≥) 20 millimeter of mercury (mmHg). Clinical significance of vital signs and out of range criterion were determined at the investigator's discretion.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 Participants
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Number of Participants With Out of Range Vital Signs
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)Population: All participants assigned to investigational product and who took at least 1 dose of investigational product.
Adverse events result in participants discontinuations from the study drug.
Outcome measures
| Measure |
Moderate Hepatic Impairment
n=10 Participants
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 Participants
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Number of Adverse Events Leading to Discontinuation
|
2 adverse events
|
0 adverse events
|
Adverse Events
Moderate Hepatic Impairment
Normal Hepatic Function
Serious adverse events
| Measure |
Moderate Hepatic Impairment
n=10 participants at risk
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 participants at risk
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Hepatobiliary disorders
Cholestasis
|
10.0%
1/10 • Number of events 1 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
0.00%
0/8 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
Other adverse events
| Measure |
Moderate Hepatic Impairment
n=10 participants at risk
Participants with moderate hepatic impairment were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
Normal Hepatic Function
n=8 participants at risk
Participants with normal hepatic function were administered PF-06651600 30 milligram (mg) once daily (QD) for 10 treatment days.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
1/10 • Number of events 1 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
0.00%
0/8 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
1/10 • Number of events 1 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
0.00%
0/8 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/10 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
12.5%
1/8 • Number of events 1 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
|
Investigations
Hepatic enzyme increased
|
10.0%
1/10 • Number of events 1 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
0.00%
0/8 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Number of events 1 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
12.5%
1/8 • Number of events 1 • Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).
Participants were only counted once per hepatic function group per event. If a participant had more than one occurrence in the same Preferred Term event category, only the most severe occurrence was counted.
|
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