Healthy
Conditions
Keywords
rifampin, pharmacokinetics, PF-06463922, drug interaction
Brief summary
The purpose of this study is to estimate the effect of rifampin on the single dose PK of PF-06463922.
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.
Interventions
DRUGPF-06463922
100 mg oral dose on day 1 in period 1 and on day 8 in period 2
DRUGrifampin
600 mg QD from day 1 to day 12 in period 2.
Sponsors
Pfizer
Study design
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study 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. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study |
|---|---|
| Age, Continuous | 36.5 years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 5 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 5 / 12 |
Outcome results
Primary
Plasma AUCinf for PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma AUCinf for PF-06463922 Given Alone and With Rifampin | 8766 nanogram (ng)*hr/ millilitre (mL) | Geometric Coefficient of Variation 19 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma AUCinf for PF-06463922 Given Alone and With Rifampin | 1299 nanogram (ng)*hr/ millilitre (mL) | Geometric Coefficient of Variation 30 |
Comparison: 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.90% CI: [12.78, 17.01]
Primary
Plasma Cmax for PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma Cmax for PF-06463922 Given Alone and With Rifampin | 621.4 ng/mL | Geometric Coefficient of Variation 26 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma Cmax for PF-06463922 Given Alone and With Rifampin | 148.4 ng/mL | Geometric Coefficient of Variation 31 |
Comparison: 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.90% CI: [21.58, 26.43]
Secondary
Plasma AUCinf for PF-06895751 When PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma AUCinf for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 4453 ng•hr/mL | Geometric Coefficient of Variation 38 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma AUCinf for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 3291 ng•hr/mL | Geometric Coefficient of Variation 60 |
Secondary
Plasma AUClast for PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma AUClast for PF-06463922 Given Alone and With Rifampin | 8597 ng•hr/mL | Geometric Coefficient of Variation 19 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma AUClast for PF-06463922 Given Alone and With Rifampin | 1200 ng•hr/mL | Geometric Coefficient of Variation 32 |
Comparison: 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.90% CI: [12.09, 16.12]
Secondary
Plasma AUClast for PF-06895751 When PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma AUClast for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 4105 ng*hr/mL | Geometric Coefficient of Variation 33 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma AUClast for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 3169 ng*hr/mL | Geometric Coefficient of Variation 60 |
Secondary
Plasma CL/F for PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma CL/F for PF-06463922 Given Alone and With Rifampin | 11.39 L/hr | Geometric Coefficient of Variation 20 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma CL/F for PF-06463922 Given Alone and With Rifampin | 76.91 L/hr | Geometric Coefficient of Variation 30 |
Secondary
Plasma Cmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma Cmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 59.02 ng/mL | Geometric Coefficient of Variation 29 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma Cmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 76.45 ng/mL | Geometric Coefficient of Variation 38 |
Secondary
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
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 | 5.521 ratio | Geometric Coefficient of Variation 56 |
Secondary
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
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 | 5.831 ratio | Geometric Coefficient of Variation 56 |
Secondary
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
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 | 1.136 ratio | Geometric Coefficient of Variation 35 |
Secondary
Plasma t1/2 for PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma t1/2 for PF-06463922 Given Alone and With Rifampin | 21.22 hr | Standard Deviation 4.12 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma t1/2 for PF-06463922 Given Alone and With Rifampin | 10.16 hr | Standard Deviation 2.43 |
Secondary
Plasma t1/2 for PF-06895751 When PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma t1/2 for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 29.14 hr | Standard Deviation 7.54 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma t1/2 for PF-06895751 When PF-06463922 Given Alone and With Rifampin | 18.43 hr | Standard Deviation 4.1 |
Secondary
Plasma Tmax for PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-06463922 100 mg | Plasma Tmax for PF-06463922 Given Alone and With Rifampin | 1.50 hr |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma Tmax for PF-06463922 Given Alone and With Rifampin | 1.51 hr |
Secondary
Plasma Tmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin.
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-06463922 100 mg | Plasma Tmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin. | 30.1 hr |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma Tmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin. | 12.0 hr |
Secondary
Plasma Vz/F for PF-06463922 Given Alone and With Rifampin
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.
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06463922 100 mg | Plasma Vz/F for PF-06463922 Given Alone and With Rifampin | 342.6 liter | Geometric Coefficient of Variation 19 |
| Rifampin 600 mg + PF-06463922 100 mg | Plasma Vz/F for PF-06463922 Given Alone and With Rifampin | 1095 liter | Geometric Coefficient of Variation 47 |
Other Pre-specified
Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
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.
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 | 1 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 | 1 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
Other Pre-specified
Number of Participants With Concomitant Treatments Meeting the Criteria of Potentially Significant Clinical Concerns
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.
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06463922 100 mg | Number of Participants With Concomitant Treatments Meeting the Criteria of Potentially Significant Clinical Concerns | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Concomitant Treatments Meeting the Criteria of Potentially Significant Clinical Concerns | 0 Participants |
Other Pre-specified
Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
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.
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Maximum (Max) PR Interval (msec) 200-<220 | 0 Participants |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max PR Interval (msec) 220-<240 | 0 Participants |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QTCF Interval (msec) >=500 | 0 Participants |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max PR Interval (msec) 240-<260 | 0 Participants |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max PR Interval (msec) >=260 | 0 Participants |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QT Interval (msec) >=500 | 0 Participants |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QTCF Interval (msec) 450-<480 | 0 Participants |
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QTCF Interval (msec) 480-<500 | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QTCF Interval (msec) >=500 | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QTCF Inc. From Baseline (msec) 30<=Chg<60 | 1 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QTCF Interval (msec) 480-<500 | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Maximum (Max) PR Interval (msec) 200-<220 | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max PR Interval (msec) 220-<240 | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max PR Interval (msec) 240-<260 | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max PR Interval (msec) >=260 | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QT Interval (msec) >=500 | 1 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns | Max QTCF Interval (msec) 450-<480 | 1 Participants |
Other Pre-specified
Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern
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
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06463922 100 mg | 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 |
| PF-06463922 100 mg | Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern | No. With Lab. Abnormalities | 5 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern | No. With Lab. Abnormalities | 6 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | 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 |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern | No. With Lab. Abnormalities | 11 Participants |
Other Pre-specified
Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern
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.
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06463922 100 mg | Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern | 0 Participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
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.
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with AEs (all Causalities) | 1 Participants |
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with SAEs (all Causalities) | 0 Participants |
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Participants with Severe AEs (all Causalities) | 0 Participants |
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Discontinued due to AEs (all Causality) | 0 Participants |
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with AEs (Treatment Related) | 1 Participants |
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with SAEs (Treatment Related) | 0 Participants |
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Participants with Severe AEs (Treatment Related) | 0 Participants |
| PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Discontinued due to AEs (Treatment Related) | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Participants with Severe AEs (all Causalities) | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Participants with Severe AEs (Treatment Related) | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Discontinued due to AEs (all Causality) | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with AEs (Treatment Related) | 4 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with SAEs (Treatment Related) | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with AEs (all Causalities) | 5 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with SAEs (all Causalities) | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Discontinued due to AEs (Treatment Related) | 0 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Participants with Severe AEs (all Causalities) | 7 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with SAEs (all Causalities) | 5 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with AEs (all Causalities) | 12 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Discontinued due to AEs (all Causality) | 12 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Participants with Severe AEs (Treatment Related) | 7 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with SAEs (Treatment Related) | 5 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | No. of Participants with AEs (Treatment Related) | 12 Participants |
| Rifampin 600 mg + PF-06463922 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related) | Discontinued due to AEs (Treatment Related) | 12 Participants |