Trial Outcomes & Findings for A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers (NCT NCT02804399)
NCT ID: NCT02804399
Last Updated: 2019-01-25
Results Overview
AUCinf is the plasma area under the plasma concentration-time profile from time 0 extrapolated to infinite time. The pharmacokinetics (PK) parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
COMPLETED
PHASE1
12 participants
Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
2019-01-25
Participant Flow
Participant milestones
| Measure |
PF-06463922 100 mg Single Dose (SD)
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1. Investigator site personnel administered study medication with ambient temperature water to a total volume of approximately 240 milliliter (mL).
|
Rifampin 600 Once a Day (QD) + PF-06463922 100 mg SD
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg tablets) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|
|
Period 1
STARTED
|
12
|
0
|
|
Period 1
COMPLETED
|
12
|
0
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Washout Period at Least 10 Days
STARTED
|
12
|
0
|
|
Washout Period at Least 10 Days
COMPLETED
|
12
|
0
|
|
Washout Period at Least 10 Days
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
0
|
12
|
|
Period 2
COMPLETED
|
0
|
11
|
|
Period 2
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
PF-06463922 100 mg Single Dose (SD)
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1. Investigator site personnel administered study medication with ambient temperature water to a total volume of approximately 240 milliliter (mL).
|
Rifampin 600 Once a Day (QD) + PF-06463922 100 mg SD
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg tablets) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
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|---|---|---|
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Period 2
Adverse Event
|
0
|
1
|
Baseline Characteristics
A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Entire Study
n=12 Participants
All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
|
|---|---|
|
Age, Continuous
|
36.5 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
AUCinf is the plasma area under the plasma concentration-time profile from time 0 extrapolated to infinite time. The pharmacokinetics (PK) parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=11 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma AUCinf for PF-06463922 Given Alone and With Rifampin
|
8766 nanogram (ng)*hr/ millilitre (mL)
Geometric Coefficient of Variation 19
|
1299 nanogram (ng)*hr/ millilitre (mL)
Geometric Coefficient of Variation 30
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
Cmax is the maximum observed plasma concentration. PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Cmax for PF-06463922 Given Alone and With Rifampin
|
621.4 ng/mL
Geometric Coefficient of Variation 26
|
148.4 ng/mL
Geometric Coefficient of Variation 31
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
AUClast is the plasma area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma AUClast for PF-06463922 Given Alone and With Rifampin
|
8597 ng•hr/mL
Geometric Coefficient of Variation 19
|
1200 ng•hr/mL
Geometric Coefficient of Variation 32
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
Tmax is the time for maximum observed plasma concentration (Cmax). The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Tmax for PF-06463922 Given Alone and With Rifampin
|
1.50 hr
Interval 0.683 to 2.0
|
1.51 hr
Interval 1.0 to 4.0
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
Terminal plasma half-life (t1/2) is the time measured for the plasma concentration of drug to decrease by one half. The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=11 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma t1/2 for PF-06463922 Given Alone and With Rifampin
|
21.22 hr
Standard Deviation 4.12
|
10.16 hr
Standard Deviation 2.43
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
CL/F is the apparent oral clearance. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=11 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma CL/F for PF-06463922 Given Alone and With Rifampin
|
11.39 L/hr
Geometric Coefficient of Variation 20
|
76.91 L/hr
Geometric Coefficient of Variation 30
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg administration with rifampin in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
Vz/F is the apparent volume of distribution (only after single dose).The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=11 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Vz/F for PF-06463922 Given Alone and With Rifampin
|
342.6 liter
Geometric Coefficient of Variation 19
|
1095 liter
Geometric Coefficient of Variation 47
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
AUClast was the plasma area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period. PF-06895751 was the metabolite of PF-06463922.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma AUClast for PF-06895751 When PF-06463922 Given Alone and With Rifampin
|
4105 ng*hr/mL
Geometric Coefficient of Variation 33
|
3169 ng*hr/mL
Geometric Coefficient of Variation 60
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period. PF-06895751 was the metabolite of PF-06463922.
Outcome measures
| Measure |
PF-06463922 100 mg
n=10 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=11 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma AUCinf for PF-06895751 When PF-06463922 Given Alone and With Rifampin
|
4453 ng•hr/mL
Geometric Coefficient of Variation 38
|
3291 ng•hr/mL
Geometric Coefficient of Variation 60
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
Tmax was the time for maximum observed plasma concentration (Cmax). The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period. PF-06895751 was the metabolite of PF-06463922.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Tmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin.
|
30.1 hr
Interval 24.0 to 36.1
|
12.0 hr
Interval 6.0 to 36.1
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
T1/2 was the terminal plasma half-life. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period. PF-06895751 was the metabolite of PF-06463922.
Outcome measures
| Measure |
PF-06463922 100 mg
n=10 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=11 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma t1/2 for PF-06895751 When PF-06463922 Given Alone and With Rifampin
|
29.14 hr
Standard Deviation 7.54
|
18.43 hr
Standard Deviation 4.10
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
Cmax was the maximum observed plasma concentration. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period. PF-06895751 was the metabolite of PF-06463922.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Cmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin
|
59.02 ng/mL
Geometric Coefficient of Variation 29
|
76.45 ng/mL
Geometric Coefficient of Variation 38
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
Cmax was the maximum observed plasma concentration of PF-06463922 and PF-06895751 ( metabolite of PF-06463922). The molecular weight adjusted metabolite/parent ratio (PF-06895751/PF-06463922) for Cmax was presented. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax (MRCmax) of PF-06463922 and Its Metabolite: When PF-06463922 Given Alone and With Rifampin
|
0.2094 ratio
Geometric Coefficient of Variation 29
|
1.136 ratio
Geometric Coefficient of Variation 35
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
AUClast was the plasma area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration of PF-06463922 and PF-06895751 ( metabolite of PF-06463922). The molecular weight adjusted metabolite/parent ratio (PF-06895751/PF-06463922) for AUClast was presented. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period. PF-06895751 was the metabolite of PF-06463922.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUClast (MRAUClast) of PF-06463922 and Its Metabolite: When PF-06463922 Given Alone and With Rifampin
|
1.053 ratio
Geometric Coefficient of Variation 24
|
5.831 ratio
Geometric Coefficient of Variation 56
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
AUCinf was the plasma area under the plasma concentration-time profile from time 0 extrapolated to infinite time of PF-06463922 and PF-06895751 ( metabolite of PF-06463922). The molecular weight adjusted metabolite/parent ratio (PF-06895751/PF-06463922) for AUCinf was presented. The PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
PF-06463922 100 mg
n=10 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=10 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Plasma Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUCinf (MRAUCinf) of PF-06463922 and Its Metabolite: When PF-06463922 Given Alone and With Rifampin
|
1.166 ratio
Geometric Coefficient of Variation 25
|
5.521 ratio
Geometric Coefficient of Variation 56
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to about 18 days after the first PF-06463922 dosePopulation: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
The total number of participants with laboratory test abnormalities was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis and some other tests (including follicle-simulating hormone\[FSH\], urine drug screening, hepatitis B surface antigen \[HBsAg\], hepatitis B core antibody \[HBcAb\], hepatitis C virus antibody \[HCVAb\] and human immunodeficiency virus \[HIV\]. Clinical significance was judged by the investigator.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern
No. of Participants Evaluable for Lab. Abnormality
|
12 Participants
|
12 Participants
|
12 Participants
|
|
Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern
No. With Lab. Abnormalities
|
5 Participants
|
6 Participants
|
11 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to about 18 days after the first PF-06463922 dose.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated physical examination focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Clinical significance was judged by the investigator.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern
|
0 Participants
|
0 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to about 18 days after the first PF-06463922 dose.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
Criteria for potentially clinically important changes in vital signs were defined as: supine and standing systolic blood pressure (SBP) of less than (\<90) millimeters of mercury (mm Hg) or change in supine and standing SBP more than or equal to (\>=) 30 mm Hg; supine and standing diastolic blood pressure (DBP) of \< 50 mm Hg or change in supine and standing DBP of \>= 20 mm Hg; supine and standing pulse rate of \< 40 or \>120 beats per minute (bpm). Figure "99999" signifies data not measurable/applicable. Maximum Decrease is abbreviated as Max.Dec., and Maximum Increase is abbreviated as Max.Inc. n is the number of participants contributing to the parameter, not applicable is abbreviated as N/A.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Supine SBP (mmHg) <90
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Standing SBP (mmHg) <90
|
—
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Supine DBP (mmHg) <50
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Standing DBP (mmHg) <50
|
—
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Supine PR (BPM) >120
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Supine PR (BPM) <40
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Standing PR (BPM) >120
|
—
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Standing PR (BPM) <40
|
—
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Max.Dec. From Baseline in Supine SBP (mm Hg) >=30
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Max.Dec. From Baseline in Supine DBP (mm Hg) >=20
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Max.Inc. From Baseline in Supine SBP (mm Hg) >=30
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Max.Inc. From Baseline in Supine DBP (mm Hg) >=20
|
0 Participants
|
0 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to about 18 days after the first PF-06463922 dose.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
PR interval was the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization. Criteria for potentially clinically important changes (chg) in ECG were defined as: absolute values of PR interval \>=200 to \<220 msec, \>=220 to \<240 msec, \>=240 to \<260 msec and \>=260 msec. Increase from baseline \>=40, \<60, \>=60 and \<80, \>=80, and relative change from baseline \>25%. The beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval corrected using the Fridericia formular (QTCF) of 450 to \<480 msec, 480 to \<500 msec and \>=500 msec, or an increase of 30 to \<60 msec of \>=60 msec. Maximum is abbreviated as Max.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Maximum (Max) PR Interval (msec) 200-<220
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max PR Interval (msec) 220-<240
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max PR Interval (msec) 240-<260
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max PR Interval (msec) >=260
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max QT Interval (msec) >=500
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max QTCF Interval (msec) 450-<480
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max QTCF Interval (msec) 480-<500
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max QTCF Interval (msec) >=500
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max PR Interval Inc. From Baseline (msec) 40-<60
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max PR Interval Inc. From Baseline (msec) 60-<80
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max PR Interval Inc. From Baseline (msec) >=80
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max PR Interval Inc.From Baseline(msec)PctChg>25%
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max QTCF Inc. From Baseline (msec) 30<=Chg<60
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Max QTCF Inc. From Baseline (msec) Chg>=60
|
0 Participants
|
0 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to about 18 days after the first PF-06463922 dose.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
Participants abstained from all concomitant treatments, except for the treatment of adverse events. Limited use of non-prescription medications that were not believed to affect participant safety or the overall results of the study might be permitted on a case by case basis following approval by the sponsor. All participants were questioned about concomitant treatment at each clinic visit. Treatments taken within 28 days before the first dose of study investigational product were documented as a prior treatment. Treatment taken after the first dose of study investigational product were documented as concomitant treatments. Females taking hormone replacement therapy might be eligible to participate in this study if they were willing to discontinue therapy at least 28 days prior to the first dose of study treatment and remained off hormonal therapy for duration of the study. Clinical significance was judged by the investigator.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Number of Participants With Concomitant Treatments Meeting the Criteria of Potentially Significant Clinical Concerns
|
0 Participants
|
0 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to about 18 days after the first PF-06463922 dose.Population: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a casual relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: 1) resulted in death; 2) was life threatening (immediate risk of death); 3) required inpatient hospitalization or prolongation of existing hospitalization; 4) resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); 5) resulted in congenital anomaly/birth defect. TEAE included both non-serious adverse events and serious adverse events.
Outcome measures
| Measure |
PF-06463922 100 mg
n=12 Participants
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 Participants
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
No. of Participants with AEs (all Causalities)
|
1 Participants
|
5 Participants
|
12 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
No. of Participants with SAEs (all Causalities)
|
0 Participants
|
0 Participants
|
5 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
Participants with Severe AEs (all Causalities)
|
0 Participants
|
0 Participants
|
7 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
Discontinued due to AEs (all Causality)
|
0 Participants
|
0 Participants
|
12 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
No. of Participants with AEs (Treatment Related)
|
1 Participants
|
4 Participants
|
12 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
No. of Participants with SAEs (Treatment Related)
|
0 Participants
|
0 Participants
|
5 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
Participants with Severe AEs (Treatment Related)
|
0 Participants
|
0 Participants
|
7 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
Discontinued due to AEs (Treatment Related)
|
0 Participants
|
0 Participants
|
12 Participants
|
Adverse Events
PF-06463922 100 mg
Rifampin 600 mg QD
Rifampin 600 mg + PF-06463922 100 mg
Serious adverse events
| Measure |
PF-06463922 100 mg
n=12 participants at risk
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg QD
n=12 participants at risk
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal for 9 days, except for rifampin dose on Day 8, which was administered simultaneously with PF-06463922.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 participants at risk
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.00%
0/12
|
0.00%
0/12
|
41.7%
5/12
|
Other adverse events
| Measure |
PF-06463922 100 mg
n=12 participants at risk
PF-06463922 was administered following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours) as 4 \* 25 milligram (mg) tablets on Day 1 of Period 1.
|
Rifampin 600 mg QD
n=12 participants at risk
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal for 9 days, except for rifampin dose on Day 8, which was administered simultaneously with PF-06463922.
|
Rifampin 600 mg + PF-06463922 100 mg
n=12 participants at risk
Rifampin 600 mg once daily was administered 1 hour before or 2 hours after a meal from Day 1 to Day 9 of Period 2, except for rifampin dose on Day 8 of Period 2, which was administered simultaneously with PF-06463922. PF-06463922 100 mg (4 \* 25 mg table) and rifampin were administered (rifampin followed by PF-06463922) following an overnight fast of at least 10 hours at approximately 0800 hours (plus or minus 2 hours).
|
|---|---|---|---|
|
Eye disorders
Dry eye
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Eye disorders
Photophobia
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Defaecation urgency
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
2/12
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12
|
0.00%
0/12
|
75.0%
9/12
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12
|
0.00%
0/12
|
25.0%
3/12
|
|
General disorders
Asthenia
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
General disorders
Fatigue
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
|
General disorders
Hangover
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
General disorders
Hunger
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.00%
0/12
|
0.00%
0/12
|
58.3%
7/12
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
2/12
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12
|
0.00%
0/12
|
25.0%
3/12
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place