Trial Outcomes & Findings for A Study To Assess Pharmacodynamics, Safety And Tolerability Of PF-05221304 And PF-06865571 Co-Administered For 6 Weeks In Adults With Non-Alcoholic Fatty Liver Disease. (NCT NCT03776175)

Last Updated: 2020-09-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

99 participants

Primary outcome timeframe

Baseline, Day 42

Results posted on

2020-09-23

Participant Flow

Participant milestones

Participant milestones
Measure	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.	PF-05221304 15mg + Placebo Participants were randomized to receive PF-05221304 15 milligram (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.	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.	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.
Treatment Period (42 Days) STARTED	14	29	28	28
Treatment Period (42 Days) Treated	14	29	28	28
Treatment Period (42 Days) COMPLETED	13	22	24	26
Treatment Period (42 Days) NOT COMPLETED	1	7	4	2
Follow-Up Period (35 Days) STARTED	13	22	24	26
Follow-Up Period (35 Days) COMPLETED	13	22	24	24
Follow-Up Period (35 Days) NOT COMPLETED	0	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	PF-05221304 15mg + Placebo Participants were randomized to receive PF-05221304 15 milligram (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.	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.	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.
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) Withdrawal by Subject	1	2	3	0
Treatment Period (42 Days) Unable to attend study visits	0	2	0	0
Follow-Up Period (35 Days) Lost to Follow-up	0	0	0	2

Baseline Characteristics

A Study To Assess Pharmacodynamics, Safety And Tolerability Of PF-05221304 And PF-06865571 Co-Administered For 6 Weeks In Adults With Non-Alcoholic Fatty Liver Disease.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=14 Participants 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.	PF-05221304 15mg + Placebo n=29 Participants 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.	PF-06865571 300 mg + Placebo n=28 Participants 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.	PF-05221304 15 mg + PF-06865571 300 mg n=28 Participants 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.	Total n=99 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=93 Participants	22 Participants n=4 Participants	26 Participants n=27 Participants	25 Participants n=483 Participants	83 Participants n=36 Participants
Age, Categorical >=65 years	4 Participants n=93 Participants	7 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	16 Participants n=36 Participants
Sex: Female, Male Female	7 Participants n=93 Participants	14 Participants n=4 Participants	15 Participants n=27 Participants	10 Participants n=483 Participants	46 Participants n=36 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	15 Participants n=4 Participants	13 Participants n=27 Participants	18 Participants n=483 Participants	53 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=93 Participants	17 Participants n=4 Participants	13 Participants n=27 Participants	21 Participants n=483 Participants	61 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=93 Participants	12 Participants n=4 Participants	14 Participants n=27 Participants	7 Participants n=483 Participants	37 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	3 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	6 Participants n=36 Participants
Race (NIH/OMB) White	13 Participants n=93 Participants	25 Participants n=4 Participants	26 Participants n=27 Participants	25 Participants n=483 Participants	89 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants 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.	PF-05221304 15mg + Placebo n=22 Participants 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.	PF-06865571 300 mg + Placebo n=24 Participants 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.	PF-05221304 15 mg + PF-06865571 300 mg n=26 Participants 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.
Percent Change From Baseline in Whole Liver Proton Density Fat Fraction (PDFF) at Day 42	8.14 percent change Interval -8.56 to 27.89	-40.01 percent change Interval -47.0 to -32.09	-30.14 percent change Interval -37.97 to -21.33	-40.13 percent change Interval -46.58 to -32.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants 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.	PF-05221304 15mg + Placebo n=29 Participants 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.	PF-06865571 300 mg + Placebo n=28 Participants 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.	PF-05221304 15 mg + PF-06865571 300 mg n=28 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants With AEs	3 Participants	10 Participants	10 Participants	10 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants With SAEs	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants 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.	PF-05221304 15mg + Placebo n=29 Participants 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.	PF-06865571 300 mg + Placebo n=27 Participants 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.	PF-05221304 15 mg + PF-06865571 300 mg n=26 Participants 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.
Number of Participants With Laboratory Abnormalities	6 Participants	17 Participants	11 Participants	6 Participants

SECONDARY outcome

Timeframe: 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.

Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants 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.	PF-05221304 15mg + Placebo n=29 Participants 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.	PF-06865571 300 mg + Placebo n=28 Participants 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.	PF-05221304 15 mg + PF-06865571 300 mg n=26 Participants 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.
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	7.0 millimeter of mercury Standard Deviation 7.77	9.6 millimeter of mercury Standard Deviation 11.38	7.5 millimeter of mercury Standard Deviation 12.58
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	3.9 millimeter of mercury Standard Deviation 7.15	5.0 millimeter of mercury Standard Deviation 7.20	4.3 millimeter of mercury Standard Deviation 8.11
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	-8.9 millimeter of mercury Standard Deviation 7.69	-9.2 millimeter of mercury Standard Deviation 10.69	-12.0 millimeter of mercury Standard Deviation 12.54
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	-7.7 millimeter of mercury Standard Deviation 7.58	-7.3 millimeter of mercury Standard Deviation 6.69	-7.2 millimeter of mercury Standard Deviation 8.09

SECONDARY outcome

Timeframe: Baseline, Post- last dose of study drug (up to Day 42)

Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants 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.	PF-05221304 15mg + Placebo n=29 Participants 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.	PF-06865571 300 mg + Placebo n=28 Participants 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.	PF-05221304 15 mg + PF-06865571 300 mg n=26 Participants 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.
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	8.1 beats per minute Standard Deviation 9.35	6.8 beats per minute Standard Deviation 9.13	6.9 beats per minute Standard Deviation 8.69
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	-2.9 beats per minute Standard Deviation 7.25	-7.5 beats per minute Standard Deviation 7.47	-5.8 beats per minute Standard Deviation 7.91

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants 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.	PF-05221304 15mg + Placebo n=29 Participants 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.	PF-06865571 300 mg + Placebo n=28 Participants 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.	PF-05221304 15 mg + PF-06865571 300 mg n=26 Participants 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.
Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria QTcF: Change >60 msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria PR interval: %Change >=25/50%	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria QRS interval: %Change >=50%	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Meeting Pre-Specified Electrocardiogram (ECG) Criteria QTcF: Change >30 msec and <=60 msec	0 Participants	2 Participants	0 Participants	1 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PF-05221304 15mg + Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

PF-06865571 300 mg + Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

PF-05221304 |15mg Q12H + |PF-06865571 |300mg Q12H

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=14 participants at risk 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.	PF-05221304 15mg + Placebo n=29 participants at risk 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.	PF-06865571 300 mg + Placebo n=28 participants at risk 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.	PF-05221304 \|15mg Q12H + \|PF-06865571 \|300mg Q12H n=28 participants at risk Participants were randomized to receive PF-05221304 15 mg tablets and PF-06865571 300 mg tablets, orally, twice daily for 42 days. Participants were followed up to maximum of 35 days after last dose of study drug.
Infections and infestations Abscess jaw	0.00% 0/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.6% 1/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.

Other adverse events

Other adverse events
Measure	Placebo n=14 participants at risk 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.	PF-05221304 15mg + Placebo n=29 participants at risk 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.	PF-06865571 300 mg + Placebo n=28 participants at risk 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.	PF-05221304 \|15mg Q12H + \|PF-06865571 \|300mg Q12H n=28 participants at risk Participants were randomized to receive PF-05221304 15 mg tablets and PF-06865571 300 mg tablets, orally, twice daily for 42 days. Participants were followed up to maximum of 35 days after last dose of study drug.
Gastrointestinal disorders Abdominal pain	7.1% 1/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.6% 1/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Gastrointestinal disorders Constipation	7.1% 1/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.4% 1/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.6% 1/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Gastrointestinal disorders Diarrhoea	0.00% 0/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.4% 1/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	7.1% 2/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
General disorders Pyrexia	7.1% 1/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Infections and infestations Folliculitis	7.1% 1/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Infections and infestations Urinary tract infection	0.00% 0/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	6.9% 2/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.6% 1/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Investigations Blood thyroid stimulating hormone increased	7.1% 1/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Metabolism and nutrition disorders Hypertriglyceridaemia	7.1% 1/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Metabolism and nutrition disorders Type 2 diabetes mellitus	7.1% 1/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.4% 1/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Nervous system disorders Headache	0.00% 0/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	3.4% 1/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	7.1% 2/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.
Skin and subcutaneous tissue disorders Rash	0.00% 0/14 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/29 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	7.1% 2/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.	0.00% 0/28 • Baseline up to 35 days from last dose of study drug or early termination (maximum up to Day 77 days) Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population included all participants who received at least 1 dose of investigational product post-randomization.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER