A 12-week Study To Evaluate PF-06291874 Once a Day in Adults With T2DM Inadequately Controlled On Metformin

A 12-week, Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of Once Daily Pf-06291874 Administration In Adults With Type 2 Diabetes Mellitus Inadequately Controlled On Metformin

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02554877

Enrollment

206

Registered

2015-09-18

Start date

2015-10-31

Completion date

2016-08-31

Last updated

2017-08-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

Brief summary

The purpose of this study is to determine whether PF-06291874 is effective in the treatment T2DM

Detailed description

This will be a randomized, double blind, stratified, placebo controlled, parallel group study conducted in T2DM subjects receiving background metformin therapy. Subjects will complete screening procedures to determine eligibility, followed by an 8 week metformin stabilization period prior to randomization. In addition, subjects taking other OADs, in combination with metformin, will undergo a washout during this period, in which non metformin OAD medications will be temporarily discontinued for the duration of the trial. Following confirmation of study eligibility criteria at randomization, subjects will be stratified into 2 groups based on the use of concomitant statin therapy. Each stratum will be randomized across treatment groups, such that the number of subjects taking concomitant statin therapy and those not taking statin therapy will be approximately balanced across treatment groups.

Interventions

DRUGPF-06291874

study drug to be given as an oral tablet at 30, 60 or 100 mg

DRUGPlacebo

oral tablet

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

1. Males or non-childbearing potential females between the ages of 18 (or the minimum country specific age of consent if \>18) and 70 years, inclusive, at the screening visit (V1) with the diagnosis of T2DM;Female subjects who are not of childbearing potential 2. Subjects who have been on a stable dose of metformin either alone or in combination with one additional acceptable OAD 3. HbA1c at the Screen Visit (V1), as assessed by study specific central laboratory, is 7-11% if on metformin monotherapy; is 6.5-9.5% if on dual combination therapy (metformin plus 1)

Exclusion criteria

1. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes; 2. Fasting plasma glucose levels \>270 mg/dL (15.0 mmol/L) at the screening and run in visit, (as assessed by study specific central laboratory) confirmed by a single repeat, if deemed necessary 3. History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class III IV heart failure, or transient ischemic attack within 6 months of screening; 4. Any medical condition possibly affecting study drug absorption (eg, gastrectomy or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency 5. Subjects with a creatinine clearance \<60 mL/min as determined by the Cockcroft Gault equation (listed below) using serum creatinine measured at screening, confirmed via a single repeat, if deemed necessary 6. Subject with a positive result for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Ab) or hepatitis C virus (HCV) antibodies 7. Screening seated systolic blood pressure \>160 mm Hg and/or diastolic blood pressure \>105 mm Hg after at least a 5 minute rest. Blood pressure determined as the mean of triplicate measurements collected with approximately 2 minutes of rest between measurements 8. Screening supine 12 lead ECG demonstrating a corrected QT (QTc) \>470 msec; or a QRS interval \>120 msec. If QTc exceeds 470 msec or QRS exceeds 120 msec, the ECG may be repeated 2 more times with an interval of 2-4 minutes between each measurement and the mean of the 3 values used to determine the subject's eligibility 9. Subjects with an arm circumference \>52 cm measured at the midpoint of the length of the upper arm; 10. History (within the last 6 months) of regular alcohol consumption exceeding 14 drinks per week for men and 7 drinks a week for women. (1 drink = 5 ounces of wine (150 mL) or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor); 11. Treatment with thiazolidinediones (TZDs), or subcutaneously administered anti diabetic agents (eg, insulin, exenatide, liraglutide, pramlintide) within 6 weeks prior to V1; 12. Subjects with a known hypersensitivity or intolerance to a glucagon receptor antagonist, or known prior participation in a trial involving PF 06291874;

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo	Baseline, Week 12	HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Baseline was defined as the last pre-dose measurement prior to first double blind dosing for the study.

Secondary

Measure	Time frame	Description
Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Baseline, Weeks 2,4,8 and 12	Fasting plasma glucose response changed from baseline at Weeks 2,4,8 and 12. Baseline was defined as the average of the measurements obtained during Day 14 visit window and Day 1 pre-dose measurement. n represented the available number of participants for analysis at post-baseline days.
Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	Week 12	HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Number of Participants With Laboratory Test Abnormalities	Baseline up to 98 days	The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.
Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Baseline up to Day 98	ECG criteria of potential clinical concern were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): \>=140 milliseconds (msec); \>=50% increase from baseline; 2), 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 (PR interval): \>=300 msec; \>=25 percent (%) increase when baseline \>200 msec; or increase \>=50% when baseline less than or equal to (\<=)200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec, \>=480-\<500 msec, \>=500 msec; increase from baseline \>=30 - \<60, \>=60 msec.
Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Baseline up to Day 98	Vital signs included seated supine systolic and diastolic blood pressure (BP) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (\<) 90 mm Hg; diastolic BP (DBP) \>=20 mm Hg change from baseline, diastolic \<50 mm Hg; 2), pulse rate \<40 or greater than (\>) 120 beats per minute (bpm).
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	Baseline up to Day 119	An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug; the event need not necessarily have a causal relationship with the treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reasons: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. An HAE was identified by characteristic symptoms or blood glucose levels. Any events occurring following start of treatment (defined as blinded therapy, including single blind placebo administration on Day 14) or increasing in severity were counted as treatment emergent AE.
Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Baseline, Weeks 2, 4, 8	HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Baseline was defined as the last pre-dose measurement prior to first double blind dosing for the study. n represented the available number of participants for analysis at post-baseline days.
Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Baseline, Weeks 2, 4, 8 and 12	Triglycerides percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days. Triglycerides MMRM was not appropriate as the data were very skewed and not normally distributed, therefore per SAP non-parametric analysis were reported, presenting medians and CIs for medians, instead. If the data had many outliers even after the log transformation the following non parametric analysis was presented instead of the MMRM. An outlier was defined as any data point falling outside of 3.5 x standard deviations the median.
Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Baseline, Weeks 2, 4, 8 and 12	Total cholesterol percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Baseline, Weeks 2, 4, 8 and 12	High density lipoprotein-cholesterol (HDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Baseline, Weeks 2, 4, 8 and 12	Non-HDL-C percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Baseline, Weeks 2, 4, 8 and 12	The body weight change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Baseline, Weeks 2, 4, 8 and 12	Fasting low density lipoprotein-cholesterol (LDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

Countries

Canada, United States

Participant flow

Participants by arm

Arm	Count
Placebo Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	51
PF-06291874 30 mg Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	51
PF-06291874 60 mg Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	52
PF-06291874 100 mg Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	52
Total	206

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	2	0	0	1
Overall Study	Did not meet entrance criteria	0	0	1	0
Overall Study	Insufficient clinical response	4	0	0	0
Overall Study	Lost to Follow-up	1	1	1	2
Overall Study	No longer met eligibility criteria	1	0	1	1
Overall Study	No longer willing to participate	0	2	2	0
Overall Study	Other	1	3	0	3
Overall Study	Protocol Violation	3	1	1	0

Baseline characteristics

Characteristic	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg	Total
Age, Continuous	56.6 years STANDARD_DEVIATION 6.3	58.1 years STANDARD_DEVIATION 6.9	57.1 years STANDARD_DEVIATION 7.1	57.4 years STANDARD_DEVIATION 7.9	57.3 years STANDARD_DEVIATION 7
Sex: Female, Male Female	22 Participants	20 Participants	24 Participants	21 Participants	87 Participants
Sex: Female, Male Male	29 Participants	31 Participants	28 Participants	31 Participants	119 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	— / —	— / —	— / —	— / —
other Total, other adverse events	6 / 51	5 / 51	2 / 52	7 / 52
serious Total, serious adverse events	2 / 51	1 / 51	0 / 52	2 / 52

Outcome results

Primary

Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo

HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Baseline was defined as the last pre-dose measurement prior to first double blind dosing for the study.

Time frame: Baseline, Week 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo	0.18 percentage of HbA1c	Standard Deviation 0.834
PF-06291874 30 mg	Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo	-0.68 percentage of HbA1c	Standard Deviation 0.778
PF-06291874 60 mg	Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo	-0.91 percentage of HbA1c	Standard Deviation 0.765
PF-06291874 100 mg	Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo	-0.92 percentage of HbA1c	Standard Deviation 0.809

Comparison: Placebo was the reference and each of the active doses was the test for Week 12p-value: <0.000195% CI: [-1.34, -0.48]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12p-value: <0.000195% CI: [-1.59, -0.73]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: <0.000195% CI: [-1.6, -0.74]Mixed Models Analysis

Secondary

Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12

Fasting plasma glucose response changed from baseline at Weeks 2,4,8 and 12. Baseline was defined as the average of the measurements obtained during Day 14 visit window and Day 1 pre-dose measurement. n represented the available number of participants for analysis at post-baseline days.

Time frame: Baseline, Weeks 2,4,8 and 12

Population: All participants randomized and who had received at least 1 dose of randomized treatment. n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 2 Change from Baseline(n=49,48,48,47)	11.0 mg/dL	Standard Deviation 28.5
Placebo	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 4 Change from Baseline(n=45,47,47,47)	3.4 mg/dL	Standard Deviation 29.22
Placebo	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 8 Change from Baseline(n=39,44,47,45)	-1.8 mg/dL	Standard Deviation 42.57
Placebo	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 12 Change from Baseline(n=39,43,46,45)	-0.6 mg/dL	Standard Deviation 31.64
PF-06291874 30 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 4 Change from Baseline(n=45,47,47,47)	-26.8 mg/dL	Standard Deviation 29.68
PF-06291874 30 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 8 Change from Baseline(n=39,44,47,45)	-19.9 mg/dL	Standard Deviation 35.93
PF-06291874 30 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 12 Change from Baseline(n=39,43,46,45)	-18.5 mg/dL	Standard Deviation 30.19
PF-06291874 30 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 2 Change from Baseline(n=49,48,48,47)	-25.2 mg/dL	Standard Deviation 26.95
PF-06291874 60 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 8 Change from Baseline(n=39,44,47,45)	-35.4 mg/dL	Standard Deviation 32.5
PF-06291874 60 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 4 Change from Baseline(n=45,47,47,47)	-34.7 mg/dL	Standard Deviation 39.15
PF-06291874 60 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 12 Change from Baseline(n=39,43,46,45)	-32.8 mg/dL	Standard Deviation 35.24
PF-06291874 60 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 2 Change from Baseline(n=49,48,48,47)	-32.4 mg/dL	Standard Deviation 35.31
PF-06291874 100 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 12 Change from Baseline(n=39,43,46,45)	-31.9 mg/dL	Standard Deviation 35.56
PF-06291874 100 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 4 Change from Baseline(n=45,47,47,47)	-30.9 mg/dL	Standard Deviation 32.55
PF-06291874 100 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 2 Change from Baseline(n=49,48,48,47)	-32.5 mg/dL	Standard Deviation 32.26
PF-06291874 100 mg	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12	Week 8 Change from Baseline(n=39,44,47,45)	-31.8 mg/dL	Standard Deviation 26.57

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: <0.000195% CI: [-47.96, -27.7]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: <0.000195% CI: [-54.98, -34.72]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: <0.000195% CI: [-58.81, -38.37]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: <0.000195% CI: [-42.52, -18.74]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: <0.000195% CI: [-51.13, -27.35]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: <0.000195% CI: [-50.22, -26.38]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.002395% CI: [-31.88, -7.05]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: <0.000195% CI: [-49.27, -24.69]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: <0.000195% CI: [-47.55, -22.72]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.001495% CI: [-31.81, -7.73]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12p-value: <0.000195% CI: [-47.17, -23.35]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12p-value: <0.000195% CI: [-48.43, -24.46]Mixed Models Analysis

Secondary

Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8

Time frame: Baseline, Weeks 2, 4, 8

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received.n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 2 HbA1c(%)Change from Baseline(n=46,48,48,47)	0.10 percentage of HbA1c	Standard Deviation 0.363
Placebo	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 8 HbA1c(%)Change from Baseline(n=40,45,47,45)	0.15 percentage of HbA1c	Standard Deviation 0.653
Placebo	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 4 HbA1c(%)Change from Baseline(n=45,47,47,47)	0.12 percentage of HbA1c	Standard Deviation 0.426
PF-06291874 30 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 2 HbA1c(%)Change from Baseline(n=46,48,48,47)	-0.30 percentage of HbA1c	Standard Deviation 0.383
PF-06291874 30 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 8 HbA1c(%)Change from Baseline(n=40,45,47,45)	-0.65 percentage of HbA1c	Standard Deviation 0.617
PF-06291874 30 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 4 HbA1c(%)Change from Baseline(n=45,47,47,47)	-0.53 percentage of HbA1c	Standard Deviation 0.546
PF-06291874 60 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 4 HbA1c(%)Change from Baseline(n=45,47,47,47)	-0.57 percentage of HbA1c	Standard Deviation 0.444
PF-06291874 60 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 2 HbA1c(%)Change from Baseline(n=46,48,48,47)	-0.30 percentage of HbA1c	Standard Deviation 0.341
PF-06291874 60 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 8 HbA1c(%)Change from Baseline(n=40,45,47,45)	-0.90 percentage of HbA1c	Standard Deviation 0.612
PF-06291874 100 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 2 HbA1c(%)Change from Baseline(n=46,48,48,47)	-0.31 percentage of HbA1c	Standard Deviation 0.26
PF-06291874 100 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 8 HbA1c(%)Change from Baseline(n=40,45,47,45)	-0.82 percentage of HbA1c	Standard Deviation 0.512
PF-06291874 100 mg	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8	Week 4 HbA1c(%)Change from Baseline(n=45,47,47,47)	-0.49 percentage of HbA1c	Standard Deviation 0.371

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: <0.000195% CI: [-0.52, -0.26]ANCOVA

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: <0.000195% CI: [-0.57, -0.3]ANCOVA

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: <0.000195% CI: [-0.76, -0.42]ANCOVA

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: <0.000195% CI: [-0.8, -0.46]ANCOVA

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: <0.000195% CI: [-0.79, -0.46]ANCOVA

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: <0.000195% CI: [-0.93, -0.49]ANCOVA

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: <0.000195% CI: [-1.17, -0.74]ANCOVA

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: <0.000195% CI: [-1.2, -0.76]ANCOVA

Secondary

Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.

The body weight change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

Time frame: Baseline, Weeks 2, 4, 8 and 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 4 Change from Baseline(n=45,47,47,47)	-0.76 kg	Standard Deviation 3.302
Placebo	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 2 Change from Baseline(n=49,48,48,47)	-0.15 kg	Standard Deviation 1.347
Placebo	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 12 Change from Baseline(n=39,44,46,45)	-0.79 kg	Standard Deviation 1.892
Placebo	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 8 Change from Baseline(n=41,45,47,45)	-0.61 kg	Standard Deviation 1.517
PF-06291874 30 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 2 Change from Baseline(n=49,48,48,47)	0.15 kg	Standard Deviation 1.234
PF-06291874 30 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 4 Change from Baseline(n=45,47,47,47)	0.55 kg	Standard Deviation 1.231
PF-06291874 30 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 8 Change from Baseline(n=41,45,47,45)	0.44 kg	Standard Deviation 1.694
PF-06291874 30 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 12 Change from Baseline(n=39,44,46,45)	0.49 kg	Standard Deviation 2.119
PF-06291874 60 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 2 Change from Baseline(n=49,48,48,47)	-0.15 kg	Standard Deviation 1.253
PF-06291874 60 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 8 Change from Baseline(n=41,45,47,45)	0.26 kg	Standard Deviation 1.775
PF-06291874 60 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 4 Change from Baseline(n=45,47,47,47)	0.28 kg	Standard Deviation 1.219
PF-06291874 60 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 12 Change from Baseline(n=39,44,46,45)	0.31 kg	Standard Deviation 2.135
PF-06291874 100 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 4 Change from Baseline(n=45,47,47,47)	0.56 kg	Standard Deviation 2.925
PF-06291874 100 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 8 Change from Baseline(n=41,45,47,45)	0.55 kg	Standard Deviation 2.786
PF-06291874 100 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 12 Change from Baseline(n=39,44,46,45)	0.41 kg	Standard Deviation 3.216
PF-06291874 100 mg	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.	Week 2 Change from Baseline(n=49,48,48,47)	0.65 kg	Standard Deviation 3.342

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.40290% CI: [-0.33, 1.01]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.878990% CI: [-0.61, 0.73]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.034590% CI: [0.19, 1.54]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.008790% CI: [0.48, 2.08]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.026890% CI: [0.28, 1.88]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.004790% CI: [0.58, 2.19]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.011690% CI: [0.38, 1.76]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.02290% CI: [0.27, 1.66]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.002190% CI: [0.62, 2.01]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.006790% CI: [0.56, 2.26]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.022590% CI: [0.33, 2.02]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.007390% CI: [0.55, 2.25]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation. (Excluding outliers)p-value: 0.239190% CI: [-0.12, 0.73]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation. (Excluding outliers)p-value: 0.003890% CI: [0.35, 1.25]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)p-value: 0.039490% CI: [0.12, 1.02]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)p-value: 0.086290% CI: [0.02, 0.93]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)p-value: 0.002490% CI: [0.48, 1.61]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)p-value: 0.002490% CI: [0.65, 2.14]Mixed Models Analysis

Secondary

Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria

ECG criteria of potential clinical concern were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): \>=140 milliseconds (msec); \>=50% increase from baseline; 2), 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 (PR interval): \>=300 msec; \>=25 percent (%) increase when baseline \>200 msec; or increase \>=50% when baseline less than or equal to (\<=)200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec, \>=480-\<500 msec, \>=500 msec; increase from baseline \>=30 - \<60, \>=60 msec.

Time frame: Baseline up to Day 98

Population: The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval >=500 msec	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 450-<480 msec	4 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase >=60 msec	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS interval >=140 msec	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 480-<500 msec	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval increase >=25%/50%	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase 30<=-<60 msec	1 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS complex increase >=50%	1 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval >=300 msec	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS complex increase >=50%	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase >=60 msec	1 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase 30<=-<60 msec	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS interval >=140 msec	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 480-<500 msec	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 450-<480 msec	4 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval >=300 msec	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval increase >=25%/50%	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval >=500 msec	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval increase >=25%/50%	1 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval >=300 msec	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS interval >=140 msec	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 450-<480 msec	2 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS complex increase >=50%	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase 30<=-<60 msec	3 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase >=60 msec	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 480-<500 msec	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval >=500 msec	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase >=60 msec	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 450-<480 msec	2 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS interval >=140 msec	1 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval >=500 msec	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval 480-<500 msec	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval >=300 msec	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QTcF interval increase 30<=-<60 msec	5 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum QRS complex increase >=50%	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria	Maximum PR interval increase >=25%/50%	1 participants

Secondary

Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria

Vital signs included seated supine systolic and diastolic blood pressure (BP) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (\<) 90 mm Hg; diastolic BP (DBP) \>=20 mm Hg change from baseline, diastolic \<50 mm Hg; 2), pulse rate \<40 or greater than (\>) 120 beats per minute (bpm).

Time frame: Baseline up to Day 98

Population: The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting Systolic BP >=20 mm Hg	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate <40 bpm	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=20 mm Hg	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting SBP <90 mm Hg	1 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate >120 bpm	0 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=30 mm Hg	1 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting DBP <50mm Hg	1 participants
Placebo	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting SBP >=30 mm Hg	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting DBP <50mm Hg	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=30 mm Hg	2 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=20 mm Hg	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting SBP <90 mm Hg	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate <40 bpm	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate >120 bpm	0 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting SBP >=30 mm Hg	3 participants
PF-06291874 30 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting Systolic BP >=20 mm Hg	1 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate <40 bpm	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting Systolic BP >=20 mm Hg	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting SBP >=30 mm Hg	1 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=20 mm Hg	1 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting DBP <50mm Hg	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting SBP <90 mm Hg	0 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=30 mm Hg	1 participants
PF-06291874 60 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate >120 bpm	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=20 mm Hg	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting SBP <90 mm Hg	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting DBP <50mm Hg	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate <40 bpm	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Sitting Pulse Rate >120 bpm	0 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting SBP >=30 mm Hg	4 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Increase: Sitting Systolic BP >=20 mm Hg	3 participants
PF-06291874 100 mg	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria	Decrease: Sitting SBP >=30 mm Hg	0 participants

Secondary

Number of Participants With Laboratory Test Abnormalities

The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.

Time frame: Baseline up to 98 days

Population: The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants With Laboratory Test Abnormalities	49 participants
PF-06291874 30 mg	Number of Participants With Laboratory Test Abnormalities	42 participants
PF-06291874 60 mg	Number of Participants With Laboratory Test Abnormalities	40 participants
PF-06291874 100 mg	Number of Participants With Laboratory Test Abnormalities	38 participants

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).

An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug; the event need not necessarily have a causal relationship with the treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reasons: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. An HAE was identified by characteristic symptoms or blood glucose levels. Any events occurring following start of treatment (defined as blinded therapy, including single blind placebo administration on Day 14) or increasing in severity were counted as treatment emergent AE.

Time frame: Baseline up to Day 119

Population: The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	AEs	22 participants
Placebo	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	HAEs	5 participants
Placebo	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	SAEs	2 participants
PF-06291874 30 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	AEs	20 participants
PF-06291874 30 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	HAEs	1 participants
PF-06291874 30 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	SAEs	1 participants
PF-06291874 60 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	SAEs	0 participants
PF-06291874 60 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	AEs	18 participants
PF-06291874 60 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	HAEs	1 participants
PF-06291874 100 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	AEs	27 participants
PF-06291874 100 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	HAEs	2 participants
PF-06291874 100 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).	SAEs	2 participants

Secondary

Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.

HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

Time frame: Week 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received.

Arm	Measure	Group	Value (NUMBER)
Placebo	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <7%	15.38 % (percentage of participants)
Placebo	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <6.5%	5.13 % (percentage of participants)
PF-06291874 30 mg	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <6.5%	11.36 % (percentage of participants)
PF-06291874 30 mg	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <7%	29.55 % (percentage of participants)
PF-06291874 60 mg	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <7%	34.78 % (percentage of participants)
PF-06291874 60 mg	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <6.5%	13.04 % (percentage of participants)
PF-06291874 100 mg	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <7%	55.56 % (percentage of participants)
PF-06291874 100 mg	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.	HbA1c <6.5%	22.22 % (percentage of participants)

Comparison: Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C\<7%)p-value: 0.005995% CI: [1.68, 21.82]Regression, Logistic

Comparison: Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C\<7%)p-value: 0.000895% CI: [2.49, 31.96]Regression, Logistic

Comparison: Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C\<7%)p-value: <0.000195% CI: [4.34, 52.67]Regression, Logistic

Comparison: Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C\<6.5%)p-value: 0.153295% CI: [0.64, 17.47]Regression, Logistic

Comparison: Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C\<6.5%)p-value: 0.082695% CI: [0.83, 21.22]Regression, Logistic

Comparison: Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C\<6.5%)p-value: 0.027295% CI: [1.21, 25.73]Regression, Logistic

Secondary

Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12

Fasting low density lipoprotein-cholesterol (LDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

Time frame: Baseline, Weeks 2, 4, 8 and 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	5.31 % (percent change)	Standard Deviation 21.244
Placebo	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=45,47,47,47)	3.29 % (percent change)	Standard Deviation 18.485
Placebo	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,47,48,47)	0.68 % (percent change)	Standard Deviation 16.301
Placebo	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,43,46,45)	0.13 % (percent change)	Standard Deviation 18.68
PF-06291874 30 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=45,47,47,47)	0.46 % (percent change)	Standard Deviation 12.752
PF-06291874 30 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,47,48,47)	-1.41 % (percent change)	Standard Deviation 17.832
PF-06291874 30 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	2.17 % (percent change)	Standard Deviation 15.503
PF-06291874 30 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,43,46,45)	1.77 % (percent change)	Standard Deviation 17.278
PF-06291874 60 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,47,48,47)	-0.64 % (percent change)	Standard Deviation 17.154
PF-06291874 60 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	1.32 % (percent change)	Standard Deviation 17.448
PF-06291874 60 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=45,47,47,47)	-0.62 % (percent change)	Standard Deviation 18.522
PF-06291874 60 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,43,46,45)	4.20 % (percent change)	Standard Deviation 18.315
PF-06291874 100 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=45,47,47,47)	-2.07 % (percent change)	Standard Deviation 15.17
PF-06291874 100 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	1.92 % (percent change)	Standard Deviation 17.03
PF-06291874 100 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,43,46,45)	1.16 % (percent change)	Standard Deviation 19.061
PF-06291874 100 mg	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,47,48,47)	2.16 % (percent change)	Standard Deviation 16.846

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.761890% CI: [-6.66, 4.59]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.848990% CI: [-6.25, 4.96]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.469990% CI: [-3.17, 8.12]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.497990% CI: [-7.63, 3.19]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.292790% CI: [-8.85, 1.95]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.14390% CI: [-10.26, 0.6]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.737390% CI: [-7.42, 4.92]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.507590% CI: [-8.57, 3.66]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.629590% CI: [-7.99, 4.37]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.426690% CI: [-3.39, 9.69]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.203890% CI: [-1.47, 11.4]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.559290% CI: [-4.19, 8.78]Mixed Models Analysis

Secondary

Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12

High density lipoprotein-cholesterol (HDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

Time frame: Baseline, Weeks 2, 4, 8 and 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	-0.14 % (percent change)	Standard Deviation 8.086
Placebo	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	0.51 % (percent change)	Standard Deviation 11.391
Placebo	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	-1.91 % (percent change)	Standard Deviation 11.736
Placebo	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	-2.62 % (percent change)	Standard Deviation 13.237
PF-06291874 30 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	0.79 % (percent change)	Standard Deviation 10.626
PF-06291874 30 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	1.24 % (percent change)	Standard Deviation 10.292
PF-06291874 30 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	3.65 % (percent change)	Standard Deviation 12.889
PF-06291874 30 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	0.08 % (percent change)	Standard Deviation 9.345
PF-06291874 60 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	2.15 % (percent change)	Standard Deviation 10.724
PF-06291874 60 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	3.98 % (percent change)	Standard Deviation 14.288
PF-06291874 60 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	4.51 % (percent change)	Standard Deviation 10.598
PF-06291874 60 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	2.60 % (percent change)	Standard Deviation 10.739
PF-06291874 100 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	7.57 % (percent change)	Standard Deviation 15.226
PF-06291874 100 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	8.16 % (percent change)	Standard Deviation 11.776
PF-06291874 100 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	8.13 % (percent change)	Standard Deviation 13.554
PF-06291874 100 mg	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	7.71 % (percent change)	Standard Deviation 13.768

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: <0.000190% CI: [5.98, 14.3]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.855990% CI: [-3.19, 3.98]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.172990% CI: [-0.62, 6.55]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.000290% CI: [4.84, 12.06]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.883790% CI: [-3.85, 4.59]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.157390% CI: [-0.6, 7.84]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.002490% CI: [3.65, 12.11]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.153890% CI: [-0.55, 7.73]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.078990% CI: [0.28, 8.49]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.013290% CI: [2.36, 11.56]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.007990% CI: [2.85, 11.96]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.000190% CI: [6.24, 15.42]Mixed Models Analysis

Secondary

Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12

Non-HDL-C percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

Time frame: Baseline, Weeks 2, 4, 8 and 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	0.51 % (percent change)	Standard Deviation 16.195
Placebo	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	4.18 % (percent change)	Standard Deviation 21.486
Placebo	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	5.24 % (percent change)	Standard Deviation 19.222
Placebo	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	-0.48 % (percent change)	Standard Deviation 16.711
PF-06291874 30 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	1.88 % (percent change)	Standard Deviation 11.961
PF-06291874 30 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	1.76 % (percent change)	Standard Deviation 14.128
PF-06291874 30 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	2.09 % (percent change)	Standard Deviation 16.451
PF-06291874 30 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	1.00 % (percent change)	Standard Deviation 16.675
PF-06291874 60 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	-0.52 % (percent change)	Standard Deviation 16.014
PF-06291874 60 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	-0.47 % (percent change)	Standard Deviation 17.972
PF-06291874 60 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	2.67 % (percent change)	Standard Deviation 18.098
PF-06291874 60 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	0.63 % (percent change)	Standard Deviation 14.87
PF-06291874 100 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	-0.25 % (percent change)	Standard Deviation 17.666
PF-06291874 100 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	-2.40 % (percent change)	Standard Deviation 13.877
PF-06291874 100 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	2.73 % (percent change)	Standard Deviation 18.427
PF-06291874 100 mg	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	0.88 % (percent change)	Standard Deviation 13.765

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.659790% CI: [-4.01, 6.92]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.758390% CI: [-4.45, 6.49]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.351690% CI: [-2.39, 8.61]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.587790% CI: [-7.42, 3.75]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.201690% CI: [-9.92, 1.26]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.056890% CI: [-12.08, -0.89]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.382790% CI: [-8.48, 2.61]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.112690% CI: [-10.81, 0.2]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.21690% CI: [-9.73, 1.38]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.344390% CI: [-2.64, 9.72]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.303190% CI: [-2.3, 9.94]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.812990% CI: [-5.27, 7.04]Mixed Models Analysis

Secondary

Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12

Total cholesterol percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

Time frame: Baseline, Weeks 2, 4, 8 and 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	2.65 % (percent change)	Standard Deviation 14.642
Placebo	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	0.16 % (percent change)	Standard Deviation 11.863
Placebo	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	-0.87 % (percent change)	Standard Deviation 13.238
Placebo	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	3.30 % (percent change)	Standard Deviation 14.354
PF-06291874 30 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	0.39 % (percent change)	Standard Deviation 12.606
PF-06291874 30 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	1.69 % (percent change)	Standard Deviation 8.763
PF-06291874 30 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	1.53 % (percent change)	Standard Deviation 10.569
PF-06291874 30 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	2.28 % (percent change)	Standard Deviation 12.26
PF-06291874 60 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	1.02 % (percent change)	Standard Deviation 12.058
PF-06291874 60 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	-0.11 % (percent change)	Standard Deviation 12.692
PF-06291874 60 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	0.36 % (percent change)	Standard Deviation 13.732
PF-06291874 60 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	3.00 % (percent change)	Standard Deviation 13.952
PF-06291874 100 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	0.44 % (percent change)	Standard Deviation 11.674
PF-06291874 100 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	2.77 % (percent change)	Standard Deviation 10.86
PF-06291874 100 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	2.03 % (percent change)	Standard Deviation 13.986
PF-06291874 100 mg	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	4.05 % (percent change)	Standard Deviation 13.9

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.6890% CI: [-3.12, 5.2]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.51590% CI: [-2.52, 5.8]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.p-value: 0.067690% CI: [0.47, 8.85]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.802190% CI: [-4.73, 3.48]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.434690% CI: [-6.06, 2.16]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.p-value: 0.417390% CI: [-6.15, 2.09]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.703690% CI: [-5.21, 3.26]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.299390% CI: [-6.84, 1.56]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.p-value: 0.975190% CI: [-4.16, 4.32]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.140890% CI: [-0.5, 8.96]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.098690% CI: [0.02, 9.38]Mixed Models Analysis

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.p-value: 0.185190% CI: [-0.92, 8.5]Mixed Models Analysis

Secondary

Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12

Triglycerides percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days. Triglycerides MMRM was not appropriate as the data were very skewed and not normally distributed, therefore per SAP non-parametric analysis were reported, presenting medians and CIs for medians, instead. If the data had many outliers even after the log transformation the following non parametric analysis was presented instead of the MMRM. An outlier was defined as any data point falling outside of 3.5 x standard deviations the median.

Time frame: Baseline, Weeks 2, 4, 8 and 12

Population: All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm	Measure	Group	Value (MEDIAN)
Placebo	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	5.45 % (percent change)
Placebo	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	3.74 % (percent change)
Placebo	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	6.72 % (percent change)
Placebo	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	-0.72 % (percent change)
PF-06291874 30 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	6.45 % (percent change)
PF-06291874 30 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	5.08 % (percent change)
PF-06291874 30 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	7.13 % (percent change)
PF-06291874 30 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	10.55 % (percent change)
PF-06291874 60 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	2.13 % (percent change)
PF-06291874 60 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	6.67 % (percent change)
PF-06291874 60 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	-1.85 % (percent change)
PF-06291874 60 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	8.32 % (percent change)
PF-06291874 100 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week12 Percent Change from Baseline(n=39,44,46,45)	5.26 % (percent change)
PF-06291874 100 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 4 Percent Change from Baseline(n=44,47,47,47)	1.18 % (percent change)
PF-06291874 100 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 2 Percent Change from Baseline(n=49,48,48,47)	22.58 % (percent change)
PF-06291874 100 mg	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12	Week 8 Percent Change from Baseline(n=40,45,47,45)	9.47 % (percent change)

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.90% CI: [-5.86, 16.05]

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.90% CI: [-9.76, 15.48]

Comparison: Placebo was the reference and each of the active doses was the test for Week 2.90% CI: [3.91, 30.34]

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.90% CI: [-10.8, 16.22]

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.90% CI: [-10.61, 16.45]

Comparison: Placebo was the reference and each of the active doses was the test for Week 4.90% CI: [-15.08, 9.94]

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.90% CI: [-16.29, 13.03]

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.90% CI: [-20.4, 11.22]

Comparison: Placebo was the reference and each of the active doses was the test for Week 8.90% CI: [-13.66, 19.16]

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.90% CI: [-3.3, 19.02]

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.90% CI: [-16.13, 13.87]

Comparison: Placebo was the reference and each of the active doses was the test for Week 12.90% CI: [-7.07, 19.04]

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

A 12-week Study To Evaluate PF-06291874 Once a Day in Adults With T2DM Inadequately Controlled On Metformin

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo

Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12

Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8

Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.

Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria

Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria

Number of Participants With Laboratory Test Abnormalities

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).

Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.

Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12

Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12

Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12

Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12

Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12