Non-Alcoholic Fatty Liver Disease (NAFLD)
Conditions
Brief summary
This study is to assess the effect of PF 05221304 alone, PF 06865571 alone, the co administration of PF 05221304 and PF 06865571, or placebo on whole liver fat in subjects with NAFLD. In addition, this study will evaluate the safety and tolerability of co administration of PF 05221304 and PF 06865571 along with the effects on selected pharmacodynamics (PD)/exploratory parameters, compared to administration of PF 05221304 alone, PF 06865571 alone, and placebo in adults with NAFLD.
Interventions
DRUGPF-05221304 Monotherapy
Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of Placebo for PF-06865571, each to be taken twice daily for 41 days and once on Day 42.
DRUGPF-06865571 Monotherapy
Participants enrolled in this Arm will receive 300 mg dose of PF-06865571 (3 tablets of 100 mg each) and 3 tablets of Placebo for PF-05221304, all to be taken twice daily for 41 days and once on Day 42.
DRUGPlacebo
Participants enrolled in this Arm will receive 3 tablets for Placebo of PF-05221304 and 3 tablets of Placebo of PF-06865571, to be taken twice daily for 41 days and once on Day 42.
DRUGPF-05221304 and PF-06865571 Combination
Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of PF-06865571 (3 tablets of 100 mg each), each to be taken twice daily for 41 days and once on Day 42.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male subjects or female subjects of non childbearing potential * Total body weight of \>50 kg (110 lbs) and a BMI greater than or equal to 25 kg/m2 * Medical diagnosis of Type 2 Diabetes Mellitus (T2DM) being treated with no more than 1 acceptable oral antidiabetic drug OR Subjects without a diagnosis of T2DM that meet 2 or more of the following 5 criteria commonly associated with metabolic syndrome * Fasting Plasma Glucose (FPG) greater than or equal to 100 mg/dL; * Documentation of at least stage 1 hypertension or medical history of hypertension; * Fasting serum HDL C \<40 mg/dL for males and \<50 mg/dL for females, or on pharmacological agents with explicit purpose to increase HDL-C; * Fasting serum triglyceride (TG) greater than or equal to 150 mg/dL or on pharmacological agents with explicit purpose to decrease TG; * Waist circumference greater than or equal to 40 inches (102 cm) for males and 35 inches (89 cm) for females. * Liver fat greater than or equal to 8% measured by MRI PDFF
Exclusion criteria
* Subjects with acute or chronic medical or psychiatric condition. * Subjects with any of the following clinical laboratory abnormalities: * Fasting TG \>400 mg/dL; * AST, ALT, or GGT \>2.0x ULN; * Hemoglobin A1c (HbA1c) \>7.0%; * Fasting plasma glucose \>270 mg/dL; * Total bilirubin \>1.5x ULN; * Albumin \< lower limit of normal (LLN); * Platelet count \<0.95x LLN; * International normalized ratio (INR) greater than or equal to 1.3. * A positive urine test for illicit drugs. * History of regular alcohol consumption. * Seated systolic BP\>=160 mmHg and/or diastolic BP\>=100 mmHg. * Supine 12 lead ECG demonstrating a corrected QT (QTcF) interval \>450 msec or a QRS interval \>120 msec. * Subjects with an estimated GFR \<60 mL/min/1.73m2. * Evidence or diagnosis of other forms of chronic liver diseases. * Subjects with any of the following medical conditions: * Any condition possibly affecting drug absorption (eg prior bariatric surgery, gastrectomy, ileal resection); * Diagnosis of type 1 diabetes mellitus; * History of congestive heart failure, unstable angina, myocardial infarction, stroke, or transient ischemic attack; * Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin); * Active placement of medical devices in/on thoracic or abdominal cavities such as pacemakers, defibrillators; * Subjects with any anatomical or pathological abnormality that would either preclude or tend to confound the analysis of study data. * Blood donation of approximately 1 pint or more within 60 days prior to dosing. * Subjects taking prohibited concomitant medication(s) or those unwilling/unable to switch to permitted concomitant medication(s) * Weight loss of greater than or equal to 5% within 1 month prior to Screening. * Unwilling or unable to comply with the Lifestyle Requirements criteria of the protocol. * Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential; fertile male subjects who are unwilling or unable to use highly effective method(s) of contraception. * Investigator site staff members or Pfizer employees, including their family members, directly involved in the conduct of the study. * Subjects with known prior treatment with or participation in a clinical trial involving any of the IPs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42 | Baseline, Day 42 | Magnetic resonance imaging proton density fat fraction (MRI-PDFF) technique is an established method that enables quantification of fat content in the liver. It measures the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF = PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by total number of segments assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 35 days from last dose of study drug or early termination: (maximum up to Day 77) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included all serious and non-serious adverse events. |
| Number of Participants With Laboratory Abnormalities | Baseline up to 35 days last from dose of study drug or early termination (maximum up to Day 77) | Clinical chemistry: Bilirubin (milligram per deciliter \[mg/dL\]), direct bilirubin (mg/dL)\>3.0\*upper limit of normal (ULN), alanine aminotransferase international units per liter (U/L), aspartate aminotransferase (U/L), alkaline phosphatase (U/L), gamma glutamyl transferase (U/L)\>5.0\*ULN, urea nitrogen (mg/dL)\>2.0\*ULN, low density lipoprotein direct endpoint measure (mg/dL)\>1.5\*ULN, triglycerides (mg/dL)\>2.0\*ULN, creatinine based estimated glomerular filtration rate by modification of diet in renal disease equation and cystatin based eGFR by chronic kidney disease epidemiology collaboration equation (C \<60 milliliter per minute per 1.73 square of meter), very low density lipoprotein (millimoles per liter), Cholesterol \>2.0\*ULN. |
| Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Baseline, Post-last dose of study drug (up to Day 42) | Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate. |
| Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Baseline, Post- last dose of study drug (up to Day 42) | Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate. |
| Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | Baseline up to 35 days last dose of study drug or early termination (maximum up to Day 77) | ECG criteria included: 1) PR interval (milliseconds \[msec\]): baseline greater than (\>) 200 msec and maximum increase from baseline greater than or equal to (\>=) 25 percent (%) or baseline less than or equal to (\<=) 200 msec and maximum increase from baseline \>=50%; 2) QRS interval (msec): maximum increase from baseline \>=50%; 3) QT interval corrected using Fridericia's formula (QTcF): a) change from baseline \>30 msec and \<=60 msec, b) change from baseline \>60 msec. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were randomized to receive placebo (3 tablets) matched to PF-05221304 and placebo (3 tablets) matched to PF-06865571 orally, twice daily for 41 days and once on Day 42. Participants were followed up to maximum of 35 days after last dose of study drug. | 14 |
| PF-05221304 15mg + Placebo Participants were randomized to receive PF-05221304 15 mg tablets (3 tablets, each of 5 mg) and placebo (3 tablets) matched to PF-06865571, orally, twice daily for 41 days and once on Day 42. Participants were followed up to maximum of 35 days after last dose of study drug. | 29 |
| PF-06865571 300 mg + Placebo Participants were randomized to receive PF-06865571 300 mg (3 tablets, each of 100 mg) and placebo (3 tablets) matched to PF-05221304 orally, twice daily for 41 days and once on Day 42. Participants were followed up to maximum of 35 days after last dose of study drug. | 28 |
| PF-05221304 15 mg + PF-06865571 300 mg Participants were randomized to receive PF-05221304 15 mg (3 tablets, each of 5 mg) and PF-06865571 300 mg (3 tablets, each of 100 mg) orally, twice daily for 41 days and once on Day 42. Participants were followed up to maximum of 35 days after last dose of study drug. | 28 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-Up Period (35 Days) | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Treatment Period (42 Days) | Adverse Event | 0 | 1 | 1 | 0 |
| Treatment Period (42 Days) | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Treatment Period (42 Days) | Participants screened at other site | 0 | 2 | 0 | 0 |
| Treatment Period (42 Days) | Unable to attend study visits | 0 | 2 | 0 | 0 |
| Treatment Period (42 Days) | Withdrawal by Subject | 1 | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo | PF-05221304 15mg + Placebo | PF-06865571 300 mg + Placebo | PF-05221304 15 mg + PF-06865571 300 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 7 Participants | 2 Participants | 3 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 22 Participants | 26 Participants | 25 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 17 Participants | 13 Participants | 21 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 12 Participants | 14 Participants | 7 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 25 Participants | 26 Participants | 25 Participants | 89 Participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 15 Participants | 10 Participants | 46 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 13 Participants | 18 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 29 | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 3 / 14 | 6 / 29 | 6 / 28 | 1 / 28 |
| serious Total, serious adverse events | 0 / 14 | 0 / 29 | 0 / 28 | 1 / 28 |
Outcome results
Primary
Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42
Magnetic resonance imaging proton density fat fraction (MRI-PDFF) technique is an established method that enables quantification of fat content in the liver. It measures the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF = PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by total number of segments assessed.
Time frame: Baseline, Day 42
Population: Full analysis set population included all randomized participants who received at least 1 dose of investigational product and participants were assigned to the randomized treatment regardless of what treatment was received. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42 | 8.14 percent change |
| PF-05221304 15mg + Placebo | Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42 | -40.01 percent change |
| PF-06865571 300 mg + Placebo | Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42 | -30.14 percent change |
| PF-05221304 15 mg + PF-06865571 300 mg | Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42 | -40.13 percent change |
Comparison: Natural log-transformed of individual relative change from baseline to Day 42 was analyzed using the ANCOVA model with treatment as a fixed effect, natural log-transformed baseline whole liver fat by MRI-PDFF as covariate. Values were back-transformed from the log scale. 90% CI was calculated on difference in least square (LS) mean between groupsp-value: 090% CI: [-54.97, -31.65]ANCOVA
Comparison: Natural log-transformed of individual relative change from baseline to Day 42 was analyzed using the ANCOVA model with treatment as a fixed effect, natural log-transformed baseline whole liver fat by MRI-PDFF as covariate. Values were back-transformed from the log scale. 90% CI was calculated on difference LS mean between groups.p-value: 0.000790% CI: [-47.4, -20.68]ANCOVA
Comparison: Natural log-transformed of individual relative change from baseline to Day 42 was analyzed using the ANCOVA model with treatment as a fixed effect, natural log-transformed baseline whole liver fat by MRI-PDFF as covariate. Values were back-transformed from the log scale. 90% CI was calculated on difference in LS mean between groups.p-value: 090% CI: [-54.8, -32.19]ANCOVA
Comparison: Natural log-transformed of individual relative change from baseline to Day 42 was analyzed using the ANCOVA model with treatment as a fixed effect, natural log-transformed baseline whole liver fat by MRI-PDFF as covariate. Values were back-transformed from the log scale. 90% CI was calculated on difference in LS mean between groups.p-value: 0.983690% CI: [-15.66, 18.08]ANCOVA
Comparison: Natural log-transformed of individual relative change from baseline to Day 42 was analyzed using the ANCOVA model with treatment as a fixed effect, natural log-transformed baseline whole liver fat by MRI-PDFF as covariate. Values were back-transformed from the log scale. 90% CI was calculated on difference in LS mean between groups.p-value: 0.123390% CI: [-27.32, 1.06]ANCOVA
Comparison: Natural log-transformed of individual relative change from baseline to Day 42 was analyzed using the ANCOVA model with treatment as a fixed effect, natural log-transformed baseline whole liver fat by MRI-PDFF as covariate. Values were back-transformed from the log scale. 50% CI was calculated on difference in LS mean between groups.50% CI: [-6.82, 6.87]
Comparison: Natural log-transformed of individual relative change from baseline to Day 42 was analyzed using the ANCOVA model with treatment as a fixed effect, natural log-transformed baseline whole liver fat by MRI-PDFF as covariate. Values were back-transformed from the log scale. 50% CI was calculated on difference in LS mean between groups.50% CI: [-19.86, -8.35]
Secondary
Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure
Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate.
Time frame: Baseline, Post-last dose of study drug (up to Day 42)
Population: Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Systolic blood pressure | 10.8 millimeter of mercury | Standard Deviation 6.59 |
| Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Diastolic blood pressure | 6.1 millimeter of mercury | Standard Deviation 6.86 |
| Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Systolic blood pressure | -9.7 millimeter of mercury | Standard Deviation 11.12 |
| Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Diastolic blood pressure | -6.2 millimeter of mercury | Standard Deviation 7.56 |
| PF-05221304 15mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Diastolic blood pressure | 3.9 millimeter of mercury | Standard Deviation 7.15 |
| PF-05221304 15mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Systolic blood pressure | -8.9 millimeter of mercury | Standard Deviation 7.69 |
| PF-05221304 15mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Diastolic blood pressure | -7.7 millimeter of mercury | Standard Deviation 7.58 |
| PF-05221304 15mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Systolic blood pressure | 7.0 millimeter of mercury | Standard Deviation 7.77 |
| PF-06865571 300 mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Systolic blood pressure | -9.2 millimeter of mercury | Standard Deviation 10.69 |
| PF-06865571 300 mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Diastolic blood pressure | 5.0 millimeter of mercury | Standard Deviation 7.2 |
| PF-06865571 300 mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Diastolic blood pressure | -7.3 millimeter of mercury | Standard Deviation 6.69 |
| PF-06865571 300 mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Systolic blood pressure | 9.6 millimeter of mercury | Standard Deviation 11.38 |
| PF-05221304 15 mg + PF-06865571 300 mg | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Diastolic blood pressure | -7.2 millimeter of mercury | Standard Deviation 8.09 |
| PF-05221304 15 mg + PF-06865571 300 mg | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Diastolic blood pressure | 4.3 millimeter of mercury | Standard Deviation 8.11 |
| PF-05221304 15 mg + PF-06865571 300 mg | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum increase: Systolic blood pressure | 7.5 millimeter of mercury | Standard Deviation 12.58 |
| PF-05221304 15 mg + PF-06865571 300 mg | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Blood Pressure | Maximum decrease: Systolic blood pressure | -12.0 millimeter of mercury | Standard Deviation 12.54 |
Secondary
Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate
Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate.
Time frame: Baseline, Post- last dose of study drug (up to Day 42)
Population: Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum increase: Pulse rate | 7.5 beats per minute | Standard Deviation 8.56 |
| Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum decrease: Pulse rate | -3.4 beats per minute | Standard Deviation 7.62 |
| PF-05221304 15mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum decrease: Pulse rate | -2.9 beats per minute | Standard Deviation 7.25 |
| PF-05221304 15mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum increase: Pulse rate | 8.1 beats per minute | Standard Deviation 9.35 |
| PF-06865571 300 mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum increase: Pulse rate | 6.8 beats per minute | Standard Deviation 9.13 |
| PF-06865571 300 mg + Placebo | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum decrease: Pulse rate | -7.5 beats per minute | Standard Deviation 7.47 |
| PF-05221304 15 mg + PF-06865571 300 mg | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum increase: Pulse rate | 6.9 beats per minute | Standard Deviation 8.69 |
| PF-05221304 15 mg + PF-06865571 300 mg | Maximum Change (Increase or Decrease) From Baseline to Post-last Dose of Study Drug in Vital Signs: Pulse Rate | Maximum decrease: Pulse rate | -5.8 beats per minute | Standard Deviation 7.91 |
Secondary
Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria
ECG criteria included: 1) PR interval (milliseconds \[msec\]): baseline greater than (\>) 200 msec and maximum increase from baseline greater than or equal to (\>=) 25 percent (%) or baseline less than or equal to (\<=) 200 msec and maximum increase from baseline \>=50%; 2) QRS interval (msec): maximum increase from baseline \>=50%; 3) QT interval corrected using Fridericia's formula (QTcF): a) change from baseline \>30 msec and \<=60 msec, b) change from baseline \>60 msec.
Time frame: Baseline up to 35 days last dose of study drug or early termination (maximum up to Day 77)
Population: Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure and Number Analyzed signifies number of participants evaluable for specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QRS interval: %Change >=50% | 0 Participants |
| Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | PR interval: %Change >=25/50% | 0 Participants |
| Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >60 msec | 0 Participants |
| Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >30 msec and <=60 msec | 0 Participants |
| PF-05221304 15mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | PR interval: %Change >=25/50% | 0 Participants |
| PF-05221304 15mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QRS interval: %Change >=50% | 0 Participants |
| PF-05221304 15mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >30 msec and <=60 msec | 2 Participants |
| PF-05221304 15mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >60 msec | 0 Participants |
| PF-06865571 300 mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | PR interval: %Change >=25/50% | 0 Participants |
| PF-06865571 300 mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >30 msec and <=60 msec | 0 Participants |
| PF-06865571 300 mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QRS interval: %Change >=50% | 0 Participants |
| PF-06865571 300 mg + Placebo | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >60 msec | 0 Participants |
| PF-05221304 15 mg + PF-06865571 300 mg | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QRS interval: %Change >=50% | 0 Participants |
| PF-05221304 15 mg + PF-06865571 300 mg | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >30 msec and <=60 msec | 1 Participants |
| PF-05221304 15 mg + PF-06865571 300 mg | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | QTcF: Change >60 msec | 0 Participants |
| PF-05221304 15 mg + PF-06865571 300 mg | Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria | PR interval: %Change >=25/50% | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
Clinical chemistry: Bilirubin (milligram per deciliter \[mg/dL\]), direct bilirubin (mg/dL)\>3.0\*upper limit of normal (ULN), alanine aminotransferase international units per liter (U/L), aspartate aminotransferase (U/L), alkaline phosphatase (U/L), gamma glutamyl transferase (U/L)\>5.0\*ULN, urea nitrogen (mg/dL)\>2.0\*ULN, low density lipoprotein direct endpoint measure (mg/dL)\>1.5\*ULN, triglycerides (mg/dL)\>2.0\*ULN, creatinine based estimated glomerular filtration rate by modification of diet in renal disease equation and cystatin based eGFR by chronic kidney disease epidemiology collaboration equation (C \<60 milliliter per minute per 1.73 square of meter), very low density lipoprotein (millimoles per liter), Cholesterol \>2.0\*ULN.
Time frame: Baseline up to 35 days last from dose of study drug or early termination (maximum up to Day 77)
Population: Safety analysis population included all participants who received at least 1 dose of investigational product. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for laboratory abnormalities.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Laboratory Abnormalities | 6 Participants |
| PF-05221304 15mg + Placebo | Number of Participants With Laboratory Abnormalities | 17 Participants |
| PF-06865571 300 mg + Placebo | Number of Participants With Laboratory Abnormalities | 11 Participants |
| PF-05221304 15 mg + PF-06865571 300 mg | Number of Participants With Laboratory 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 investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included all serious and non-serious adverse events.
Time frame: Baseline up to 35 days from last dose of study drug or early termination: (maximum up to Day 77)
Population: Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 Participants |
| PF-05221304 15mg + Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 Participants |
| PF-05221304 15mg + Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 10 Participants |
| PF-06865571 300 mg + Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 10 Participants |
| PF-06865571 300 mg + Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 Participants |
| PF-05221304 15 mg + PF-06865571 300 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 10 Participants |
| PF-05221304 15 mg + PF-06865571 300 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 1 Participants |