Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis
Conditions
Brief summary
2-week study in people with nonalcoholic fatty liver disease. Study drug at 1 of 2 doses, or placebo, will be given for 14 days. Blood samples, heart monitoring, vital signs, and imaging procedures will be performed.
Interventions
DRUGPlacebo
tablet, 0 mg, 14 days, every 12 hours
DRUGPF-06865571
tablet, 50 mg, 14 days, every 12 hours
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* controlled attenuation parameter greater than or equal to 260 dB/m via FibroScan * liver fat greater than or equal to 6% via MRI
Exclusion criteria
* Chronic liver disease * Type 2 diabetes requiring drug treatment * Unable to undergo MRI * History of heart attack or stroke
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF) | Baseline (Day 1), Day 15 | MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Plasma Concentration (Cmin) For PF-06865571 | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | Cmin of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages. |
| Apparent Oral Clearance (CL/F) For PF-06865571 | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | CL/F of PF-06865571 on Day 14 was calculated as Dose/AUCtau. Geometric coefficients of variations were reported as percentages. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose of study treatment up to 28-35 days after last dose (maximum of up to 49 days) | An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs. |
| Number of Participants With Laboratory Test Abnormalities | From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, calcium, chloride, bicarbonate); urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, urine erythrocytes, urine leukocytes, hyaline casts); biomarker (total cholesterol, low-density and high-density lipoprotein cholesterol, triglycerides, fasting glucose). Participants with any of the laboratory test abnormalities were counted. |
| Time to Reach Maximum Plasma Concentration (Tmax) For PF-06865571 | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | Tmax of PF-06865571 on Day 14 was observed directly from data as time of Cmax occurrence. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities | From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) | ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): \>=140 milliseconds (msec), \>=50% change from baseline; 2) PR interval (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): \>=300 msec, \>=25% change when baseline is \> 200 msec or \>=50% change when baseline is less than or equal to (\<=) 200 msec; 3) QTcF interval (heart rate corrected QT \[time between the start of the ECG Q wave and the end of the T wave in the heart's electrical cycle\] using Fridericia's formula): absolute value of \>450 to 480 msec, \>480 to 500 msec, \>500 msec; a change from baseline of \>30 to 60 msec or \>60 msec. |
| Maximum Plasma Concentration (Cmax) For PF-06865571 | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | Cmax of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages. |
| Area Under the Plasma Concentration-Time Profile Over the Dosing Interval (AUCtau) For PF-06865571 | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | AUCtau of PF-06865571 on Day 14 was obtained by linear/log trapezoidal method. The dosing interval (tau) was 12 hours. Geometric coefficients of variations were reported as percentages. |
| Peak-to-Trough Ratio (PTR) For PF-06865571 | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | PTR of PF-06865571 on Day 14 was calculated as Cmax/Cmin. Geometric coefficients of variations were reported as percentages. |
| Number of Participants With Vital Sign Abnormalities | From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) | Vital sign categorical summarization criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine DBP greater than or equal to (\>=) 20 mmHg; 5) change from baseline (increase or decrease) in supine SBP \>=30 mmHg. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo tablets orally every 12 hours (Q12H) for 14 days. | 16 |
| PF-06865571 50 mg Participants received PF-06865571 50 mg tablets orally Q12H for 14 days. | 17 |
| PF-06865571 300 mg Participants received PF-06865571 300 mg tablets orally Q12H for 14 days. | 15 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Study dosing paused by sponsor | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | PF-06865571 50 mg | PF-06865571 300 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 45.8 years STANDARD_DEVIATION 10.5 | 47.0 years STANDARD_DEVIATION 8 | 48.3 years STANDARD_DEVIATION 5.5 | 47.0 years STANDARD_DEVIATION 8.2 |
| Age, Customized 18-44 years | 7 Participants | 4 Participants | 3 Participants | 14 Participants |
| Age, Customized 45-64 years | 9 Participants | 13 Participants | 12 Participants | 34 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 14 Participants | 9 Participants | 36 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 12 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 | 1 / 15 |
| other Total, other adverse events | 2 / 16 | 12 / 17 | 8 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 | 1 / 15 |
Outcome results
Primary
Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF)
MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of study treatment (PF-06865571 or placebo) and had whole liver fat assessed at Day 15.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF) | -10.94 percentage of whole liver fat |
| PF-06865571 50 mg | Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF) | -32.62 percentage of whole liver fat |
| PF-06865571 300 mg | Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF) | -41.14 percentage of whole liver fat |
p-value: <0.00180% CI: [-31.28, -16.7]ANCOVA
p-value: <0.00180% CI: [-39.78, -27.47]ANCOVA
Secondary
Apparent Oral Clearance (CL/F) For PF-06865571
CL/F of PF-06865571 on Day 14 was calculated as Dose/AUCtau. Geometric coefficients of variations were reported as percentages.
Time frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
Population: All randomized participants who received at least 1 dose of PF-06865571 (50 mg or 300 mg) and had CL/F data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Oral Clearance (CL/F) For PF-06865571 | 48.30 liters per hour (L/hr) | Geometric Coefficient of Variation 35 |
| PF-06865571 50 mg | Apparent Oral Clearance (CL/F) For PF-06865571 | 38.49 liters per hour (L/hr) | Geometric Coefficient of Variation 26 |
Secondary
Area Under the Plasma Concentration-Time Profile Over the Dosing Interval (AUCtau) For PF-06865571
AUCtau of PF-06865571 on Day 14 was obtained by linear/log trapezoidal method. The dosing interval (tau) was 12 hours. Geometric coefficients of variations were reported as percentages.
Time frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
Population: All randomized participants who received at least 1 dose of PF-06865571 (50 mg or 300 mg) and had AUCtau data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-Time Profile Over the Dosing Interval (AUCtau) For PF-06865571 | 1036 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| PF-06865571 50 mg | Area Under the Plasma Concentration-Time Profile Over the Dosing Interval (AUCtau) For PF-06865571 | 7798 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
Secondary
Maximum Plasma Concentration (Cmax) For PF-06865571
Cmax of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages.
Time frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
Population: All randomized participants who received at least 1 dose of PF-06865571 (50 mg or 300 mg) and had Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) For PF-06865571 | 345.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| PF-06865571 50 mg | Maximum Plasma Concentration (Cmax) For PF-06865571 | 2001 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Secondary
Minimum Plasma Concentration (Cmin) For PF-06865571
Cmin of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages.
Time frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
Population: All randomized participants who received at least 1 dose of PF-06865571 (50 mg or 300 mg) and had Cmin data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Minimum Plasma Concentration (Cmin) For PF-06865571 | 6.609 ng/mL | Geometric Coefficient of Variation 75 |
| PF-06865571 50 mg | Minimum Plasma Concentration (Cmin) For PF-06865571 | 57.79 ng/mL | Geometric Coefficient of Variation 68 |
Secondary
Number of Participants With Electrocardiogram (ECG) Abnormalities
ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): \>=140 milliseconds (msec), \>=50% change from baseline; 2) PR interval (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): \>=300 msec, \>=25% change when baseline is \> 200 msec or \>=50% change when baseline is less than or equal to (\<=) 200 msec; 3) QTcF interval (heart rate corrected QT \[time between the start of the ECG Q wave and the end of the T wave in the heart's electrical cycle\] using Fridericia's formula): absolute value of \>450 to 480 msec, \>480 to 500 msec, \>500 msec; a change from baseline of \>30 to 60 msec or \>60 msec.
Time frame: From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)
Population: All randomized participants who received at least 1 dose of study treatment (PF-06865571 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >500 msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change >30 to <=60 msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change >60 msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QRS interval >=140 msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | %Change in QRS interval >=50% | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | %Change in PR interval >=25/50% | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >450 to <=480 msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >480 to <=500 msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | PR interval >=300 msec | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QRS interval >=140 msec | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >500 msec | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | PR interval >=300 msec | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >450 to <=480 msec | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change >30 to <=60 msec | 1 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | %Change in PR interval >=25/50% | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | %Change in QRS interval >=50% | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change >60 msec | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >480 to <=500 msec | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change >60 msec | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QRS interval >=140 msec | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | %Change in PR interval >=25/50% | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | %Change in QRS interval >=50% | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >450 to <=480 msec | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >480 to <=500 msec | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF >500 msec | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change >30 to <=60 msec | 1 Participants |
| PF-06865571 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | PR interval >=300 msec | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, calcium, chloride, bicarbonate); urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, urine erythrocytes, urine leukocytes, hyaline casts); biomarker (total cholesterol, low-density and high-density lipoprotein cholesterol, triglycerides, fasting glucose). Participants with any of the laboratory test abnormalities were counted.
Time frame: From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)
Population: All randomized participants who received at least 1 dose of study treatment (PF-06865571 or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities | 5 Participants |
| PF-06865571 50 mg | Number of Participants With Laboratory Test Abnormalities | 8 Participants |
| PF-06865571 300 mg | Number of Participants With Laboratory Test Abnormalities | 6 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs.
Time frame: From first dose of study treatment up to 28-35 days after last dose (maximum of up to 49 days)
Population: All randomized participants who received at least 1 dose of study treatment (PF-06865571 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| PF-06865571 50 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 12 Participants |
| PF-06865571 50 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 9 Participants |
| PF-06865571 300 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
Secondary
Number of Participants With Vital Sign Abnormalities
Vital sign categorical summarization criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine DBP greater than or equal to (\>=) 20 mmHg; 5) change from baseline (increase or decrease) in supine SBP \>=30 mmHg.
Time frame: From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)
Population: All randomized participants who received at least 1 dose of study treatment (PF-06865571 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Sign Abnormalities | Pulse rate >120 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP <90 mm Hg | 0 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP <50 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP increase >=20 mm Hg | 2 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | Pulse rate <40 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP decrease >=30 mm Hg | 1 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP decrease >=20 mm Hg | 1 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP increase >=30 mm Hg | 2 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP increase >=30 mm Hg | 1 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP increase >=20 mm Hg | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP <90 mm Hg | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP decrease >=30 mm Hg | 1 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP <50 mmHg | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP decrease >=20 mm Hg | 1 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Pulse rate <40 bpm | 0 Participants |
| PF-06865571 50 mg | Number of Participants With Vital Sign Abnormalities | Pulse rate >120 bpm | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP <50 mmHg | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Pulse rate >120 bpm | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Pulse rate <40 bpm | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP <90 mm Hg | 0 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP decrease >=20 mm Hg | 2 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP increase >=20 mm Hg | 3 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP increase >=30 mm Hg | 2 Participants |
| PF-06865571 300 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP decrease >=30 mm Hg | 0 Participants |
Secondary
Peak-to-Trough Ratio (PTR) For PF-06865571
PTR of PF-06865571 on Day 14 was calculated as Cmax/Cmin. Geometric coefficients of variations were reported as percentages.
Time frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
Population: All randomized participants who received at least 1 dose of PF-06865571 (50 mg or 300 mg) and had Cmax and non-zero Cmin data for PTR evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak-to-Trough Ratio (PTR) For PF-06865571 | 53.17 ratio of concentrations | Geometric Coefficient of Variation 68 |
| PF-06865571 50 mg | Peak-to-Trough Ratio (PTR) For PF-06865571 | 34.63 ratio of concentrations | Geometric Coefficient of Variation 75 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) For PF-06865571
Tmax of PF-06865571 on Day 14 was observed directly from data as time of Cmax occurrence.
Time frame: Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
Population: All randomized participants who received at least 1 dose of PF-06865571 (50 mg or 300 mg) and had Tmax data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Maximum Plasma Concentration (Tmax) For PF-06865571 | 2.00 hours |
| PF-06865571 50 mg | Time to Reach Maximum Plasma Concentration (Tmax) For PF-06865571 | 2.00 hours |