A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02804399
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 3
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

The purpose of this study is to estimate the effect of rifampin on the single dose PK of PF-06463922.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: PF-06463922; Drug: rifampin	Phase 1

Detailed Description

This will be a Phase 1, open-label, 2-period, 2-treatment, fixed-sequence, cross-over study in approximately 12 healthy subjects employing administration of a single oral dose of PF-06463922 in the fasted state alone, and with multiple dosing of rifampin 600 mg once a day to estimate the effect of multiple dose rifampin on the single dose PK of PF-06463922.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase One, Open Label, Two-period, Two-treatment, Fixed Sequence, Cross-over Study To Estimate The Effect Of Multiple Dose Rifampin On The Single Dose Pharmacokinetics Of Pf-06463922 In Healthy Volunteers.
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: all subjects subjects will receive a 100 mg single oral dose of PF-06463922 followed by a 100 mg single dose of PF-06463922 combined with 600 mg QD dose of rifampin with at least 10 days of washout period between two PF-06463922 doses.	Drug: PF-06463922; 100 mg oral dose on day 1 in period 1 and on day 8 in period 2; Other Names: lorlatinib ; Drug: rifampin; 600 mg QD from day 1 to day 12 in period 2.; Other Names: rifampicin

Outcome Measures

Primary Outcome Measures

1. Plasma AUCinf for PF-06463922 Given Alone and With Rifampin [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.]

   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.

2. Plasma Cmax for PF-06463922 Given Alone and With Rifampin [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.]

   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.

Secondary Outcome Measures

1. Plasma AUClast for PF-06463922 Given Alone and With Rifampin [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.]

   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.

2. Plasma Tmax for PF-06463922 Given Alone and With Rifampin [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.]

   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.

3. Plasma t1/2 for PF-06463922 Given Alone and With Rifampin [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.]

   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.

4. Plasma CL/F for PF-06463922 Given Alone and With Rifampin [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.]

   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.

5. Plasma Vz/F for PF-06463922 Given Alone and With Rifampin [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.]

   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.

6. Plasma AUClast for PF-06895751 When PF-06463922 Given Alone and With Rifampin [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.]

   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.

7. Plasma AUCinf for PF-06895751 When PF-06463922 Given Alone and With Rifampin [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.]

   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.

8. Plasma Tmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin. [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.]

   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.

9. Plasma t1/2 for PF-06895751 When PF-06463922 Given Alone and With Rifampin [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.]

   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.

10. Plasma Cmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin [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.]

    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.

11. 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 [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.]

    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.

12. 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 [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.]

    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.

13. 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 [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.]

    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.

Other Outcome Measures

1. Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern [Baseline to about 18 days after the first PF-06463922 dose]

   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.

2. Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern [Baseline to about 18 days after the first PF-06463922 dose.]

   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.

3. Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns [Baseline to about 18 days after the first PF-06463922 dose.]

   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.

4. Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns [Baseline to about 18 days after the first PF-06463922 dose.]

   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.

5. Number of Participants With Concomitant Treatments Meeting the Criteria of Potentially Significant Clinical Concerns [Baseline to about 18 days after the first PF-06463922 dose.]

   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.

6. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) [Baseline to about 18 days after the first PF-06463922 dose.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy female subjects of non-childbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive

• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease

• Any condition possibly affecting drug absorption

• Positive urine drug screen

• History of HIV, Hep B or Hep C

• History of regular alcohol consumption

• History of cardiac arrhythmia, history of AV block, history of symptomatic bradycardia, history of QTc prolongation

• History of pancreatitis or hyperlipidemia, elevated lipase

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer New Haven Clinical Research Unit	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02804399
• Other Study ID Numbers: B7461011; RIFAMPIN DDI STUDY
• First Posted: Jun 17, 2016
• Last Update Posted: Jan 25, 2019
• Last Verified: Aug 1, 2018

• Keywords provided by Pfizer: rifampin; pharmacokinetics; PF-06463922; drug interaction
• Additional relevant MeSH terms: Rifampin

Study Results

Participant Flow

Arm/Group Title	PF-06463922 100 mg Single Dose (SD)	Rifampin 600 Once a Day (QD) + PF-06463922 100 mg SD
Arm/Group Description	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 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 Title: Period 1
STARTED	12	0
COMPLETED	12	0
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	12	0
COMPLETED	12	0
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	0	12
COMPLETED	0	11
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Entire Study
Arm/Group Description	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.
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.5 (11.1)
Sex: Female, Male (Count of Participants)
Female	1 8.3%
Male	11 91.7%

Outcome Measures

1. Primary Outcome

Title	Plasma AUCinf for PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	11
Geometric Mean (Geometric Coefficient of Variation) [nanogram (ng)*hr/ millilitre (mL)]	8766 (19)	1299 (30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-06463922 100 mg, Rifampin 600 mg + PF-06463922 100 mg
	Comments	Mixed model was fitted to obtain ratio of geometric means of Rifampin 600 mg QD + PF-06463922 100 mg SD (test) to PF-06463922 100 mg SD (reference) and the results are presented as percentage. 90% CI was calculated on ratio of geometric means.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Mean
	Estimated Value	14.74
	Confidence Interval	(2-Sided) 90%; 12.78 to 17.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Plasma Cmax for PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	621.4 (26)	148.4 (31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-06463922 100 mg, Rifampin 600 mg + PF-06463922 100 mg
	Comments	Mixed model was fitted to obtain ratio of geometric means of Rifampin 600 mg QD + PF-06463922 100 mg SD (test) to PF-06463922 100 mg SD (reference) and the results are presented as percentage. 90% CI was calculated on ratio of geometric means.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Mean
	Estimated Value	23.88
	Confidence Interval	(2-Sided) 90%; 21.58 to 26.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Plasma AUClast for PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [ng•hr/mL]	8597 (19)	1200 (32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-06463922 100 mg, Rifampin 600 mg + PF-06463922 100 mg
	Comments	Mixed model was fitted to obtain ratio of geometric means of Rifampin 600 mg QD + PF-06463922 100 mg SD (test) to PF-06463922 100 mg SD (reference) and the results are presented as percentage. 90% CI was calculated on ratio of geometric means.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Mean
	Estimated Value	13.96
	Confidence Interval	(2-Sided) 90%; 12.09 to 16.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Plasma Tmax for PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Median (Full Range) [hr]	1.50	1.51

5. Secondary Outcome

Title	Plasma t1/2 for PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	11
Mean (Standard Deviation) [hr]	21.22 (4.12)	10.16 (2.43)

6. Secondary Outcome

Title	Plasma CL/F for PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	11
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	11.39 (20)	76.91 (30)

7. Secondary Outcome

Title	Plasma Vz/F for PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	11
Geometric Mean (Geometric Coefficient of Variation) [liter]	342.6 (19)	1095 (47)

8. Secondary Outcome

Title	Plasma AUClast for PF-06895751 When PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	4105 (33)	3169 (60)

9. Secondary Outcome

Title	Plasma AUCinf for PF-06895751 When PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	10	11
Geometric Mean (Geometric Coefficient of Variation) [ng•hr/mL]	4453 (38)	3291 (60)

10. Secondary Outcome

Title	Plasma Tmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin.
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Median (Full Range) [hr]	30.1	12.0

11. Secondary Outcome

Title	Plasma t1/2 for PF-06895751 When PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	10	11
Mean (Standard Deviation) [hr]	29.14 (7.54)	18.43 (4.10)

12. Secondary Outcome

Title	Plasma Cmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	59.02 (29)	76.45 (38)

13. Secondary Outcome

Title	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
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.2094 (29)	1.136 (35)

14. Secondary Outcome

Title	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
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [ratio]	1.053 (24)	5.831 (56)

15. Secondary Outcome

Title	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
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	10	10
Geometric Mean (Geometric Coefficient of Variation) [ratio]	1.166 (25)	5.521 (56)

16. Other Pre-specified Outcome

Title	Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern
Description	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.
Time Frame	Baseline to about 18 days after the first PF-06463922 dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg QD	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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 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).
Measure Participants	12	12	12
No. of Participants Evaluable for Lab. Abnormality	12 100%	12 NaN	12 NaN
No. With Lab. Abnormalities	5 41.7%	6 NaN	11 NaN

17. Other Pre-specified Outcome

Title	Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern
Description	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.
Time Frame	Baseline to about 18 days after the first PF-06463922 dose.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Count of Participants [Participants]	0 0%	0 NaN

18. Other Pre-specified Outcome

Title	Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
Description	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.
Time Frame	Baseline to about 18 days after the first PF-06463922 dose.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Supine SBP (mmHg) <90	0 0%	1 NaN
Standing SBP (mmHg) <90	0 0%
Supine DBP (mmHg) <50	0 0%	0 NaN
Standing DBP (mmHg) <50	0 0%
Supine PR (BPM) >120	0 0%	0 NaN
Supine PR (BPM) <40	0 0%	0 NaN
Standing PR (BPM) >120	0 0%
Standing PR (BPM) <40	0 0%
Max.Dec. From Baseline in Supine SBP (mm Hg) >=30	0 0%	0 NaN
Max.Dec. From Baseline in Supine DBP (mm Hg) >=20	0 0%	0 NaN
Max.Inc. From Baseline in Supine SBP (mm Hg) >=30	0 0%	1 NaN
Max.Inc. From Baseline in Supine DBP (mm Hg) >=20	0 0%	0 NaN

19. Other Pre-specified Outcome

Title	Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
Description	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.
Time Frame	Baseline to about 18 days after the first PF-06463922 dose.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Maximum (Max) PR Interval (msec) 200-<220	0 0%	0 NaN
Max PR Interval (msec) 220-<240	0 0%	0 NaN
Max PR Interval (msec) 240-<260	0 0%	0 NaN
Max PR Interval (msec) >=260	0 0%	0 NaN
Max QT Interval (msec) >=500	0 0%	1 NaN
Max QTCF Interval (msec) 450-<480	0 0%	1 NaN
Max QTCF Interval (msec) 480-<500	0 0%	0 NaN
Max QTCF Interval (msec) >=500	0 0%	0 NaN
Max PR Interval Inc. From Baseline (msec) 40-<60	0 0%	0 NaN
Max PR Interval Inc. From Baseline (msec) 60-<80	0 0%	0 NaN
Max PR Interval Inc. From Baseline (msec) >=80	0 0%	0 NaN
Max PR Interval Inc.From Baseline(msec)PctChg>25%	0 0%	0 NaN
Max QTCF Inc. From Baseline (msec) 30<=Chg<60	0 0%	1 NaN
Max QTCF Inc. From Baseline (msec) Chg>=60	0 0%	0 NaN

20. Other Pre-specified Outcome

Title	Number of Participants With Concomitant Treatments Meeting the Criteria of Potentially Significant Clinical Concerns
Description	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.
Time Frame	Baseline to about 18 days after the first PF-06463922 dose.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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).
Measure Participants	12	12
Count of Participants [Participants]	0 0%	0 NaN

21. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
Description	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.
Time Frame	Baseline to about 18 days after the first PF-06463922 dose.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-06463922 100 mg	Rifampin 600 mg QD	Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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 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).
Measure Participants	12	12	12
No. of Participants with AEs (all Causalities)	1 8.3%	5 NaN	12 NaN
No. of Participants with SAEs (all Causalities)	0 0%	0 NaN	5 NaN
Participants with Severe AEs (all Causalities)	0 0%	0 NaN	7 NaN
Discontinued due to AEs (all Causality)	0 0%	0 NaN	12 NaN
No. of Participants with AEs (Treatment Related)	1 8.3%	4 NaN	12 NaN
No. of Participants with SAEs (Treatment Related)	0 0%	0 NaN	5 NaN
Participants with Severe AEs (Treatment Related)	0 0%	0 NaN	7 NaN
Discontinued due to AEs (Treatment Related)	0 0%	0 NaN	12 NaN

Adverse Events

Arm/Group Title	PF-06463922 100 mg		Rifampin 600 mg QD		Rifampin 600 mg + PF-06463922 100 mg
Arm/Group Description	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 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 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).
All Cause Mortality
	PF-06463922 100 mg		Rifampin 600 mg QD		Rifampin 600 mg + PF-06463922 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PF-06463922 100 mg		Rifampin 600 mg QD		Rifampin 600 mg + PF-06463922 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		5/12 (41.7%)
Hepatobiliary disorders
Drug-induced liver injury	0/12 (0%)		0/12 (0%)		5/12 (41.7%)
Other (Not Including Serious) Adverse Events
	PF-06463922 100 mg		Rifampin 600 mg QD		Rifampin 600 mg + PF-06463922 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		5/12 (41.7%)		11/12 (91.7%)
Eye disorders
Dry eye	0/12 (0%)		1/12 (8.3%)		1/12 (8.3%)
Photophobia	0/12 (0%)		1/12 (8.3%)		1/12 (8.3%)
Gastrointestinal disorders
Abdominal pain	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Abdominal pain lower	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Defaecation urgency	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Diarrhoea	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Dyspepsia	0/12 (0%)		0/12 (0%)		2/12 (16.7%)
Flatulence	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Nausea	0/12 (0%)		0/12 (0%)		9/12 (75%)
Retching	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Vomiting	0/12 (0%)		0/12 (0%)		3/12 (25%)
General disorders
Asthenia	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Fatigue	0/12 (0%)		1/12 (8.3%)		1/12 (8.3%)
Hangover	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Hunger	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Hepatobiliary disorders
Drug-induced liver injury	0/12 (0%)		0/12 (0%)		7/12 (58.3%)
Metabolism and nutrition disorders
Decreased appetite	0/12 (0%)		0/12 (0%)		2/12 (16.7%)
Musculoskeletal and connective tissue disorders
Muscle twitching	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Nervous system disorders
Dizziness	1/12 (8.3%)		0/12 (0%)		3/12 (25%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	0/12 (0%)		1/12 (8.3%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/12 (0%)		1/12 (8.3%)		0/12 (0%)

Limitations/Caveats

As all participants receiving co-administration of PF-06463922 (100 mg SD) with rifampin (600 mg QD) experienced drug-induced liver injury AEs, all 12 participants were discontinued from further rifampin treatment after 9 days but not 12 days.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.