Safety, Tolerability, Pharmacokinetics And Pharmacodynami... | NCT02175121

Safety, Tolerability, Pharmacokinetics And Pharmacodynami... | NCT02175121 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Treatment A- Placebo	Placebo Comparator	Drug: Placebo
Treatment B- PF-06291874	Experimental	Drug: PF-06291874
Treatment C- PF-06291874	Experimental	Drug: PF-06291874
Treatment D- PF-06291874	Experimental	Drug: PF-06291874
Treatment E- PF-06291874	Experimental	Drug: PF-06291874

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Tablet, once daily for 28 days	Treatment A- Placebo
PF-06291874

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), or Serious Adverse Events (SAEs), or Hypoglycemic Adverse Events (HAE) or Withdrawals Due to Adverse Events (AEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. An HAE was identified by characteristic symptoms or blood glucose levels. TEAEs are events between first dose of study drug and up to 10-14 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.	Baseline up to 10-14 days after last dose of study drug, up to 42 days
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.	Baseline up to 10-14 days after last dose of study drug, up to 42 days
Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern	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).	Baseline up to 10-14 days after last dose of study drug, up to 42 days
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Mean Daily Glucose	The mean daily glucose was determined from the area under the concentration (AUC) of the glucose concentrations measured at nominal times 0, 0.5, 1, 1.5, 2, 4, 6, 10, 12, 15 and 24 hours post dose. Mean daily glucose change from baseline (defined as Day 0) on Day 28.	Baseline and Day 28

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male subjects and non-childbearing potential female subjects between the ages of 18 and 70 years old.
Body Mass Index of 18.0 to 45.4 kg/m2; and a total body weight of >50 kg
HbA1c value at the screening visit meeting once of the following criteria:
- Currently taking acceptable oral antiglycemic drug therapy within 6.5 to 9.5%
- Not currently taking any oral antiglycemic drug therapy within 7 to 10.5%
Fasting plasma glucose concentrations<270mg/dL at the screening and run-in visit, confirmed by a single repeat, if deemed necessary.
Subjects must be willing and able to perform self-tests of blood glucose at least 4 times per day, and maintain a diary for the duration of participation in the study; and therefore, subjects must be literate.

Exclusion Criteria:

History of Type 1 diabetes mellitus or secondary forms of diabetes
One or more self-reported hypoglycemic episodes of sever intensity within 3 months of screening; or 2 or more self-reported hypoglycemic episodes of severe intensity within the previous 6 months.
History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II-IV heart failure, or transient ischemic attach within 6 months of screening.
History or evidence of diabetic complications with significant end organ damage, such as
- Proliferative retinopathy and/or macular edema;
- Diabetic neuropathy complicated by neuropathic ulcers;
Screening seated systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg after at least a 5 minute seated rest. If the blood pressure exceeds this limit, the blood pressure may be repeated 2 more times following approximately 2 minutes of rest between measurements and the median of the 3 values should be used to determine subject eligibility;
Male subjects with partners currently pregnant; or male subjects capable of conceiving children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Anaheim Clinical Trials, LLC		Anaheim	California	92801	United States
Profil Institute for Clinical Research, Inc.

Label	URL
To obtain contact information for a study center near you, click here.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
FG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Lack of Efficacy		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG0040 subjects
Lost to Follow-up		FG0000 subjects FG0011 subjects FG0020 subjects FG0031 subjects FG004
Personal emergency		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Schedule conflict		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004
Time issues		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
BG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
BG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
BG003	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
BG004	PF-06291874 150 mg	Participants received PF-06291874 150 mg (two 25 mg tablets, one 100 mg tablet and one 5/25 mg placebo tablet) once daily for 28 days
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.9± 6.3 BG00156.1± 9 BG00257.8± 7.5 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00016 BG0019 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), or Serious Adverse Events (SAEs), or Hypoglycemic Adverse Events (HAE) or Withdrawals Due to Adverse Events (AEs)

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. An HAE was identified by characteristic symptoms or blood glucose levels. TEAEs are events between first dose of study drug and up to 10-14 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.

The safety analysis set was defined as all participants who received at least 1 dose of study drug.

Posted

Number

participants

Baseline up to 10-14 days after last dose of study drug, up to 42 days

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG004	PF-06291874 150 mg	Participants received PF-06291874 150 mg (two 25 mg tablets, one 100 mg tablet and one 5/25 mg placebo tablet) once daily for 28 days

Units	Counts
Participants	OG00034 OG00135 OG00234 OG003

Title

Denominators

Categories

Number of Participants With AEs

Title	Measurements
	OG00011 OG0017 OG00210 OG003

Primary

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.

The safety analysis set was defined as all participants who received at least 1 dose of study drug.

Posted

Number

participants

Baseline up to 10-14 days after last dose of study drug, up to 42 days

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Primary

Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern

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).

The safety analysis set was defined as all participants who received at least 1 dose of study drug.

Posted

Number

participants

Baseline up to 10-14 days after last dose of study drug, up to 42 days

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days

Primary

Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern

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 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 milliseconds (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.

The safety analysis set was defined as all participants who received at least 1 dose of study drug.

Posted

Number

participants

Baseline up to 10-14 days after last dose of study drug, up to 42 days

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days

Secondary

Change From Baseline in Mean Daily Glucose

The mean daily glucose was determined from the area under the concentration (AUC) of the glucose concentrations measured at nominal times 0, 0.5, 1, 1.5, 2, 4, 6, 10, 12, 15 and 24 hours post dose. Mean daily glucose change from baseline (defined as Day 0) on Day 28.

The full analysis set (FAS) was used in the analysis of the pharmacodynamic (PD) parameters. The FAS was defined as all subjects randomized and who received at least 1 dose of randomized treatment. Number of participants analyzed represents the available number of participants for analysis at post-baseline days.

Posted

Mean

Standard Deviation

mg/dL

Baseline and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days

Secondary

Change From Baseline in Fasting Plasma Glucose

Fasting plasma glucose response change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

The FAS was used in the analysis of the PD parameters. The FAS was defined as all subjects randomized and who received at least 1 dose of randomized treatment. N in change from Baseline when different, represents the available number of participants for analysis at post-baseline days.

Posted

Mean

Standard Deviation

mg/dL

Baseline, Day 14 and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Triglycerides

Triglycerides percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

The FAS was used in the analysis of the PD parameters. The FAS was defined as all subjects randomized and who received at least 1 dose of randomized treatment. N in percent change from Baseline when different, represents the available number of participants for analysis at post-baseline days.

Posted

Mean

Standard Deviation

% (percent change)

Baseline, Day 14 and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Total Cholesterol

Total cholesterol percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

Posted

Mean

Standard Deviation

% (percent change)

Baseline, Day 14 and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003

Secondary

Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)

LDL-C percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

Posted

Mean

Standard Deviation

% (percent change)

Baseline, Day 14 and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003

Secondary

Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)

HDL-C percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

Posted

Mean

Standard Deviation

% (percent change)

Baseline, Day 14 and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003

Secondary

Percent Change From Baseline in Non-HDL-C

Non-HDL-C percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

Posted

Mean

Standard Deviation

% (percent change)

Baseline, Day 14 and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Oxidized LDL

Oxidized LDL percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

The FAS was used in the analysis of the PD parameters. The FAS was defined as all subjects randomized and who received at least 1 dose of randomized treatment. Number of participants analyzed represents the available number of participants for analysis at post-baseline days.

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Large LDL Particles

Large LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Medium Small LDL Particles

Medium small LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Small LDL Particles

Small LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Very Small LDL Particles

Very small LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Total LDL Particles

Total LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in LDL Size

The LDL size percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Percent Change From Baseline in Apolipoprotein B100

The Apolipoprotein B100 was calculated as the difference between total Apolipoprotein B and Apolipoprotein B48 and analyzed the percent change from baseline (defined as mean of Day 0 and Day 1) on Day 28 (mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days

Secondary

Percent Change From Baseline in Lipoprotein A

The Lipoprotein A percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (mean of Days 28 and 29).

Posted

Mean

Standard Deviation

% (percent change)

Baseline and the mean of Days 28 and 29

ID	Title	Description
OG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
OG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 75 mg

Secondary

Maximum Plasma Concentration (Cmax)

Maximum PF-06291874 plasma concentration.

The PK analysis set was defined as all participants who received at least 1 dose of study medication. Samples for participants taking placebo were not analyzed. Number of participants analyzed represents the available number of participants for analysis at post-baseline days.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

ID	Title	Description
OG000	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG001	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 150 mg

Secondary

Time to Reach Cmax (Tmax)

Time to maximum PF-06291874 plasma concentration.

Posted

Median

Full Range

hour (hr)

Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

ID	Title	Description
OG000	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG001	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 150 mg

Secondary

Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours)

Area under the PF-06291874 plasma concentration-time profile from time zero to time tau, the dosing interval, where tau=24 hours.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

ID	Title	Description
OG000	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG001	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days

Secondary

Minimum Plasma Concentration (Cmin)

Minimum PF-06291874 plasma concentration.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

ID	Title	Description
OG000	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG001	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 150 mg

Secondary

Apparent Clearance (CL/F)

Apparent oral clearance of PF-06291874.

Posted

Geometric Mean

Geometric Coefficient of Variation

L/hr

Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

ID	Title	Description
OG000	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG001	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days
OG002	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
OG003	PF-06291874 150 mg

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days	0	34	4	34
EG001	PF-06291874 15 mg	Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days	0	35	4	35
EG002	PF-06291874 35 mg	Participants received PF-06291874 35 mg (two 5 mg tablets, one 25 mg tablet and one 100 mg placebo tablet) once daily for 28 days	0	34	8	34
EG003	PF-06291874 75 mg	Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days	1	35	6	35
EG004	PF-06291874 150 mg	Participants received PF-06291874 150 mg (two 25 mg tablets, one 100 mg tablet and one 5/25 mg placebo tablet) once daily for 28 days	0	34	6	34

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Cerebral infarction	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 affected34 at risk EG0010 affected35 at risk EG0020 affected34 at risk EG0031 affected35 at risk EG0040 affected34 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected34 at risk EG0011 affected35 at risk EG0023 affected34 at risk EG0031 affected35 at risk EG0043 affected34 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected34 at risk EG0010 affected35 at risk EG0021 affected34 at risk EG003
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected34 at risk EG0012 affected35 at risk EG0020 affected34 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected34 at risk EG0012 affected35 at risk EG0023 affected34 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected34 at risk EG0010 affected35 at risk EG0023 affected34 at risk EG003

Title

Denominators

Categories

Supine SBP <90 mm Hg

Title	Measurements
	OG0003 OG0010 OG0020 OG0030 OG0040

Supine DBP <50 mm Hg

Title	Measurements
	OG0001 OG0010 OG0020 OG003

Increase: supine SBP >=30 mm Hg

Title	Measurements
	OG0003 OG0013 OG0023 OG003

Increase: supine DBP >=20 mm Hg

Title	Measurements
	OG0001 OG0010 OG0022 OG003

Decrease: supine SBP >= 30 mm Hg

Title	Measurements
	OG0001 OG0010 OG0020 OG003

Decrease: supine DBP >=20 mm Hg

Title	Measurements
	OG0003 OG0010 OG0020 OG003

Pulse rate <40 bpm

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Pulse rate >120 bpm

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Title

Denominators

Categories

PR interval >=300 msec

Title	Measurements
	OG0000 OG0010 OG0020 OG0030 OG0040

QRS interval >=140 msec

Title	Measurements
	OG0000 OG0010 OG0020 OG003

QTcF interval 450-480 msec

Title	Measurements
	OG0002 OG0014 OG0024 OG003

QTcF interval 480-500 msec

Title	Measurements
	OG0000 OG0010 OG0021 OG003

QTcF interval >=500 msec

Title	Measurements
	OG0000 OG0010 OG0020 OG003

PR interval increase >=25%/50%

Title	Measurements
	OG0000 OG0011 OG0020 OG003

QRS interval increase >=50%

Title	Measurements
	OG0000 OG0010 OG0020 OG003

QTcF interval increase 30-60 msec

Title	Measurements
	OG0001 OG0015 OG0024 OG003

QTcF interval increase >=60 msec

Title	Measurements
	OG0000 OG0010 OG0021 OG003

Title

Denominators

Categories

Title	Measurements
	OG0006.63± 38.938(2.33 to 18.37) OG001-29.15± 25.659(-37.73 to -22.22) OG002-32.29± 29.572(-43.44 to -26.93) OG003-59.98± 29.363(-66.19 to -50.68) OG004-55.99± 39.798(-65.76 to -49.78)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Placebo was the Reference and each of the active doses was the Test.	ANCOVA	LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.	<0.0001	Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.	Mean Difference (Net)	-40.33	Standard Error of the Mean	6.75	2-Sided	90	-51.49	-29.16	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test.	ANCOVA	LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.	<0.0001	Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.	Mean Difference (Net)	-45.53	Standard Error of the Mean	6.98	2-Sided	90	-57.08	-33.99	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test.	ANCOVA	LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.	<0.0001	Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.	Mean Difference (Net)	-68.79	Standard Error of the Mean	6.73	2-Sided	90	-79.92	-57.65	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test.	ANCOVA	LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.	<0.0001	Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.	Mean Difference (Net)	-68.12	Standard Error of the Mean	6.86	2-Sided	90	-79.46	-56.78	No	Superiority or Other

Title

Denominators

Categories

Day 14 Change from Baseline (N=33,34,32,35,33)

Title	Measurements
	OG000-6.08± 29.778 OG001-21.76± 24.278 OG002-29.59± 31.552 OG003-45.59± 26.040 OG004-52.18± 30.824

Day 28 Change from Baseline (N=33,35,32,35,33)

Title	Measurements
	OG0006.11± 29.840 OG001-20.26± 23.523 OG002-26.61± 22.045 OG003

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.0060	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-16.25	Standard Error of the Mean	5.83	2-Sided	90	-25.90	-6.60	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-26.98	Standard Error of the Mean	5.94	2-Sided	90	-36.81	-17.15	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-39.60	Standard Error of the Mean	5.80	2-Sided	90	-49.20	-30.00	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-46.72	Standard Error of the Mean	5.89	2-Sided	90	-56.46	-36.98	No	Superiority or Other
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-27.07	Standard Error of the Mean	5.33	2-Sided	90	-35.89	-18.25	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-36.18	Standard Error of the Mean	5.46	2-Sided	90	-45.21	-27.14	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-51.47	Standard Error of the Mean	5.33	2-Sided	90	-60.29	-42.65	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-57.17	Standard Error of the Mean	5.41	2-Sided	90	-66.12	-48.22	No	Superiority or Other

Title

Denominators

Categories

D14 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0000.52± 47.749 OG00125.69± 93.991 OG00226.95± 100.972 OG0032.71± 63.990 OG00421.52± 86.951

D28 Percent Change from Baseline(N=33,35,32,35,33）

Title	Measurements
	OG00019.58± 26.037 OG00115.20± 29.122 OG00219.48± 28.647 OG003

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.2063	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	12.86	Standard Error of the Mean	10.13	2-Sided	90	-3.91	29.62	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.2087	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	13.03	Standard Error of the Mean	10.33	2-Sided	90	-4.05	30.11	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.5802	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	5.60	Standard Error of the Mean	10.10	2-Sided	90	-11.11	22.30	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.1553	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	14.64	Standard Error of the Mean	10.25	2-Sided	90	-2.32	31.59	No	Superiority or Other
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.7741	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-2.20	Standard Error of the Mean	7.66	2-Sided	90	-14.87	10.47	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.9588	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-0.40	Standard Error of the Mean	7.78	2-Sided	90	-13.28	12.47	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.8523	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	1.42	Standard Error of the Mean	7.61	2-Sided	90	-11.17	14.01	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.4166	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	6.30	Standard Error of the Mean	7.73	2-Sided	90	-6.49	19.08	No	Superiority or Other

Title

Denominators

Categories

D14 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0004.04± 11.024 OG0014.49± 11.036 OG0027.94± 16.059 OG0034.60± 12.888 OG00412.98± 17.177

D28 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0004.07± 7.928 OG0012.93± 11.503 OG0024.52± 11.354 OG003

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.8516	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	0.60	Standard Error of the Mean	3.22	2-Sided	90	-4.73	5.93	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.2303	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	3.97	Standard Error of the Mean	3.29	2-Sided	90	-1.48	9.42	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.7132	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	1.19	Standard Error of the Mean	3.22	2-Sided	90	-4.15	6.52	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.0034	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	9.74	Standard Error of the Mean	3.28	2-Sided	90	4.32	15.16	No	Superiority or Other
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.7394	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-0.99	Standard Error of the Mean	2.96	2-Sided	90	-5.89	3.92	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.8652	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	0.52	Standard Error of the Mean	3.03	2-Sided	90	-4.50	5.53	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.8370	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	0.61	Standard Error of the Mean	2.97	2-Sided	90	-4.30	5.52	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.0018	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	9.59	Standard Error of the Mean	3.01	2-Sided	90	4.60	14.58	No	Superiority or Other

Title

Denominators

Categories

D14 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0006.24± 15.803 OG0013.95± 14.407 OG0028.12± 23.085 OG0035.29± 15.223 OG00414.24± 21.612

D28 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0002.92± 12.046 OG0012.46± 13.472 OG0023.51± 19.507 OG003

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.6182	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-2.12	Standard Error of the Mean	4.25	2-Sided	90	-9.15	4.91	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.7028	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	1.66	Standard Error of the Mean	4.34	2-Sided	90	-5.52	8.84	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.9445	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-0.30	Standard Error of the Mean	4.25	2-Sided	90	-7.33	6.73	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.0373	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	9.07	Standard Error of the Mean	4.32	2-Sided	90	1.93	16.21	No	Superiority or Other
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.9448	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-0.29	Standard Error of the Mean	4.21	2-Sided	90	-7.25	6.67	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.9312	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	0.37	Standard Error of the Mean	4.30	2-Sided	90	-6.74	7.49	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.9791	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-0.11	Standard Error of the Mean	4.21	2-Sided	90	-7.07	6.85	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.0044	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	12.34	Standard Error of the Mean	4.28	2-Sided	90	5.26	19.41	No	Superiority or Other

Title

Denominators

Categories

D14 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0006.99± 15.590 OG0019.02± 14.884 OG00211.27± 15.720 OG00314.47± 16.884 OG00419.75± 18.172

D28 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0003.94± 11.330 OG0014.78± 9.271 OG0024.82± 13.426 OG003

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.6553	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	1.77	Standard Error of the Mean	3.96	2-Sided	90	-4.78	8.33	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.2569	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	4.61	Standard Error of the Mean	4.05	2-Sided	90	-2.09	11.30	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.0553	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	7.64	Standard Error of the Mean	3.96	2-Sided	90	1.09	14.18	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.0016	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	12.89	Standard Error of the Mean	4.01	2-Sided	90	6.26	19.53	No	Superiority or Other
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.8717	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	0.58	Standard Error of the Mean	3.58	2-Sided	90	-5.35	6.51	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.7430	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	1.20	Standard Error of the Mean	3.66	2-Sided	90	-4.86	7.26	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.2041	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	4.56	Standard Error of the Mean	3.58	2-Sided	90	-1.36	10.48	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	<0.0001	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	14.92	Standard Error of the Mean	3.63	2-Sided	90	8.92	20.92	No	Superiority or Other

Title

Denominators

Categories

D14 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0003.29± 11.686 OG0012.96± 14.179 OG0027.52± 20.983 OG0031.26± 16.181 OG00412.32± 22.192

D28 Percent Change from Baseline(N=33,35,32,35,33)

Title	Measurements
	OG0003.84± 8.728 OG0012.55± 14.319 OG0024.65± 14.309 OG003

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.9750	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	0.13	Standard Error of the Mean	4.08	2-Sided	90	-6.62	6.87	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.3396	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	3.99	Standard Error of the Mean	4.16	2-Sided	90	-2.90	10.87	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.7142	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-1.49	Standard Error of the Mean	4.07	2-Sided	90	-8.23	5.24	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 14.	Mixed Models Analysis	0.0192	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	9.78	Standard Error of the Mean	4.14	2-Sided	90	2.94	16.63	No	Superiority or Other
OG000 OG001	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.8277	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-0.84	Standard Error of the Mean	3.85	2-Sided	90	-7.20	5.52	No	Superiority or Other
OG000 OG002	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.8857	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	0.57	Standard Error of the Mean	3.93	2-Sided	90	-5.93	7.06	No	Superiority or Other
OG000 OG003	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.8824	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	-0.57	Standard Error of the Mean	3.84	2-Sided	90	-6.93	5.79	No	Superiority or Other
OG000 OG004	Placebo was the Reference and each of the active doses was the Test for Day 28.	Mixed Models Analysis	0.0192	Two-sided p-values are from MMRM with baseline value, time, treatment group, study day, statin use and treatment interaction as fixed effects. Subject was used as a random effect.	Mean Difference (Net)	9.23	Standard Error of the Mean	3.90	2-Sided	90	2.77	15.69	No	Superiority or Other

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases