Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06291874 As Oral Monotherapy To Treat Adults With Type 2 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02175121
Recruitment Status : Completed
First Posted : June 26, 2014
Results First Posted : June 15, 2016
Last Update Posted : June 15, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type II
Interventions Drug: Placebo
Drug: PF-06291874
Enrollment 172
Recruitment Details Eligibility included male participants or female participants of non-childbearing potential, 18 to 70 years of age (inclusive) who were willing and able to wash off all diabetes medications.
Pre-assignment Details  
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days 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 Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days 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
Period Title: Overall Study
Started 34 35 34 35 34
Completed 33 34 32 34 33
Not Completed 1 1 2 1 1
Reason Not Completed
Lack of Efficacy             1             0             0             0             0
Lost to Follow-up             0             1             0             1             0
Personal emergency             0             0             0             0             1
Schedule conflict             0             0             1             0             0
Time issues             0             0             1             0             0
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg Total
Hide Arm/Group Description Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days 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 Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days 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 Total of all reporting groups
Overall Number of Baseline Participants 34 35 34 35 34 172
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 35 participants 34 participants 35 participants 34 participants 172 participants
58.9  (6.3) 56.1  (9) 57.8  (7.5) 55.5  (7.6) 55.2  (7.5) 56.7  (7.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 35 participants 34 participants 35 participants 34 participants 172 participants
Female
16
  47.1%
9
  25.7%
16
  47.1%
12
  34.3%
18
  52.9%
71
  41.3%
Male
18
  52.9%
26
  74.3%
18
  52.9%
23
  65.7%
16
  47.1%
101
  58.7%
1.Primary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline up to 10-14 days after last dose of study drug, up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least 1 dose of study drug.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Measure Type: Number
Unit of Measure: participants
Number of Participants With AEs 11 7 10 11 12
Number of Participants with SAEs 0 0 0 1 0
Number of Participants with Protocol-Defined HAEs 0 0 0 1 0
Number of Participants discontinued from study 1 1 2 1 1
2.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities
Hide Description 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 10-14 days after last dose of study drug, up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least 1 dose of study drug.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Measure Type: Number
Unit of Measure: participants
31 31 24 32 30
3.Primary Outcome
Title Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern
Hide Description 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 10-14 days after last dose of study drug, up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least 1 dose of study drug.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Measure Type: Number
Unit of Measure: participants
Supine SBP <90 mm Hg 3 0 0 0 0
Supine DBP <50 mm Hg 1 0 0 0 0
Increase: supine SBP >=30 mm Hg 3 3 3 1 6
Increase: supine DBP >=20 mm Hg 1 0 2 1 0
Decrease: supine SBP >= 30 mm Hg 1 0 0 0 0
Decrease: supine DBP >=20 mm Hg 3 0 0 0 0
Pulse rate <40 bpm 0 0 0 0 0
Pulse rate >120 bpm 0 0 0 0 0
4.Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
Hide Description 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.
Time Frame Baseline up to 10-14 days after last dose of study drug, up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least 1 dose of study drug.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Measure Type: Number
Unit of Measure: participants
PR interval >=300 msec 0 0 0 0 0
QRS interval >=140 msec 0 0 0 0 0
QTcF interval 450-480 msec 2 4 4 2 3
QTcF interval 480-500 msec 0 0 1 0 1
QTcF interval >=500 msec 0 0 0 0 0
PR interval increase >=25%/50% 0 1 0 0 0
QRS interval increase >=50% 0 0 0 0 0
QTcF interval increase 30-60 msec 1 5 4 4 5
QTcF interval increase >=60 msec 0 0 1 0 0
5.Secondary Outcome
Title Change From Baseline in Mean Daily Glucose
Hide Description 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.
Time Frame Baseline and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 33 35 31 35 33
Mean (Standard Deviation)
Unit of Measure: mg/dL
6.63  (38.938) -29.15  (25.659) -32.29  (29.572) -59.98  (29.363) -55.99  (39.798)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
Method ANCOVA
Comments LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -40.33
Confidence Interval (2-Sided) 90%
-51.49 to -29.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.75
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
Method ANCOVA
Comments LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -45.53
Confidence Interval (2-Sided) 90%
-57.08 to -33.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
Method ANCOVA
Comments LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -68.79
Confidence Interval (2-Sided) 90%
-79.92 to -57.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Two-sided p-values are from analysis of Covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
Method ANCOVA
Comments LS mean difference from placebo adjusted for baseline values is derived from the ANCOVA model.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -68.12
Confidence Interval (2-Sided) 90%
-79.46 to -56.78
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.86
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose
Hide Description 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.
Time Frame Baseline, Day 14 and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Mean (Standard Deviation)
Unit of Measure: mg/dL
Day 14 Change from Baseline (N=33,34,32,35,33) -6.08  (29.778) -21.76  (24.278) -29.59  (31.552) -45.59  (26.040) -52.18  (30.824)
Day 28 Change from Baseline (N=33,35,32,35,33) 6.11  (29.840) -20.26  (23.523) -26.61  (22.045) -45.27  (22.115) -50.45  (32.045)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0060
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -16.25
Confidence Interval (2-Sided) 90%
-25.90 to -6.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -26.98
Confidence Interval (2-Sided) 90%
-36.81 to -17.15
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.94
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -39.60
Confidence Interval (2-Sided) 90%
-49.20 to -30.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -46.72
Confidence Interval (2-Sided) 90%
-56.46 to -36.98
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -27.07
Confidence Interval (2-Sided) 90%
-35.89 to -18.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -36.18
Confidence Interval (2-Sided) 90%
-45.21 to -27.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.46
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -51.47
Confidence Interval (2-Sided) 90%
-60.29 to -42.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -57.17
Confidence Interval (2-Sided) 90%
-66.12 to -48.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.41
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percent Change From Baseline in Triglycerides
Hide Description 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.
Time Frame Baseline, Day 14 and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Mean (Standard Deviation)
Unit of Measure: % (percent change)
D14 Percent Change from Baseline(N=33,35,32,35,33) 0.52  (47.749) 25.69  (93.991) 26.95  (100.972) 2.71  (63.990) 21.52  (86.951)
D28 Percent Change from Baseline(N=33,35,32,35,33) 19.58  (26.037) 15.20  (29.122) 19.48  (28.647) 20.72  (40.626) 24.96  (35.090)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2063
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.86
Confidence Interval (2-Sided) 90%
-3.91 to 29.62
Parameter Dispersion
Type: Standard Error of the mean
Value: 10.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2087
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 13.03
Confidence Interval (2-Sided) 90%
-4.05 to 30.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 10.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5802
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.60
Confidence Interval (2-Sided) 90%
-11.11 to 22.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 10.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1553
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 14.64
Confidence Interval (2-Sided) 90%
-2.32 to 31.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 10.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7741
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.20
Confidence Interval (2-Sided) 90%
-14.87 to 10.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 7.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9588
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.40
Confidence Interval (2-Sided) 90%
-13.28 to 12.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 7.78
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8523
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.42
Confidence Interval (2-Sided) 90%
-11.17 to 14.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 7.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4166
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.30
Confidence Interval (2-Sided) 90%
-6.49 to 19.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 7.73
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol
Hide Description 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.
Time Frame Baseline, Day 14 and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Mean (Standard Deviation)
Unit of Measure: % (percent change)
D14 Percent Change from Baseline(N=33,35,32,35,33) 4.04  (11.024) 4.49  (11.036) 7.94  (16.059) 4.60  (12.888) 12.98  (17.177)
D28 Percent Change from Baseline(N=33,35,32,35,33) 4.07  (7.928) 2.93  (11.503) 4.52  (11.354) 4.05  (13.061) 12.86  (17.086)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8516
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.60
Confidence Interval (2-Sided) 90%
-4.73 to 5.93
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2303
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.97
Confidence Interval (2-Sided) 90%
-1.48 to 9.42
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7132
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.19
Confidence Interval (2-Sided) 90%
-4.15 to 6.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.74
Confidence Interval (2-Sided) 90%
4.32 to 15.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7394
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.99
Confidence Interval (2-Sided) 90%
-5.89 to 3.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8652
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.52
Confidence Interval (2-Sided) 90%
-4.50 to 5.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8370
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.61
Confidence Interval (2-Sided) 90%
-4.30 to 5.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.97
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.59
Confidence Interval (2-Sided) 90%
4.60 to 14.58
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.01
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)
Hide Description 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.
Time Frame Baseline, Day 14 and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Mean (Standard Deviation)
Unit of Measure: % (percent change)
D14 Percent Change from Baseline(N=33,35,32,35,33) 6.24  (15.803) 3.95  (14.407) 8.12  (23.085) 5.29  (15.223) 14.24  (21.612)
D28 Percent Change from Baseline(N=33,35,32,35,33) 2.92  (12.046) 2.46  (13.472) 3.51  (19.507) 2.15  (17.238) 14.19  (24.128)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6182
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.12
Confidence Interval (2-Sided) 90%
-9.15 to 4.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7028
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.66
Confidence Interval (2-Sided) 90%
-5.52 to 8.84
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9445
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.30
Confidence Interval (2-Sided) 90%
-7.33 to 6.73
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0373
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.07
Confidence Interval (2-Sided) 90%
1.93 to 16.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9448
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.29
Confidence Interval (2-Sided) 90%
-7.25 to 6.67
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9312
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.37
Confidence Interval (2-Sided) 90%
-6.74 to 7.49
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9791
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.11
Confidence Interval (2-Sided) 90%
-7.07 to 6.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0044
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.34
Confidence Interval (2-Sided) 90%
5.26 to 19.41
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.28
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)
Hide Description 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.
Time Frame Baseline, Day 14 and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Mean (Standard Deviation)
Unit of Measure: % (percent change)
D14 Percent Change from Baseline(N=33,35,32,35,33) 6.99  (15.590) 9.02  (14.884) 11.27  (15.720) 14.47  (16.884) 19.75  (18.172)
D28 Percent Change from Baseline(N=33,35,32,35,33) 3.94  (11.330) 4.78  (9.271) 4.82  (13.426) 8.34  (9.013) 18.73  (24.979)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6553
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.77
Confidence Interval (2-Sided) 90%
-4.78 to 8.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2569
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.61
Confidence Interval (2-Sided) 90%
-2.09 to 11.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0553
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.64
Confidence Interval (2-Sided) 90%
1.09 to 14.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.89
Confidence Interval (2-Sided) 90%
6.26 to 19.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8717
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.58
Confidence Interval (2-Sided) 90%
-5.35 to 6.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7430
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.20
Confidence Interval (2-Sided) 90%
-4.86 to 7.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2041
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.56
Confidence Interval (2-Sided) 90%
-1.36 to 10.48
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 14.92
Confidence Interval (2-Sided) 90%
8.92 to 20.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.63
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C
Hide Description 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.
Time Frame Baseline, Day 14 and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 34 35 34 35 34
Mean (Standard Deviation)
Unit of Measure: % (percent change)
D14 Percent Change from Baseline(N=33,35,32,35,33) 3.29  (11.686) 2.96  (14.179) 7.52  (20.983) 1.26  (16.181) 12.32  (22.192)
D28 Percent Change from Baseline(N=33,35,32,35,33) 3.84  (8.728) 2.55  (14.319) 4.65  (14.309) 2.75  (17.275) 12.32  (22.758)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9750
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.13
Confidence Interval (2-Sided) 90%
-6.62 to 6.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3396
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.99
Confidence Interval (2-Sided) 90%
-2.90 to 10.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7142
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.49
Confidence Interval (2-Sided) 90%
-8.23 to 5.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 14.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0192
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.78
Confidence Interval (2-Sided) 90%
2.94 to 16.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 15 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8277
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.84
Confidence Interval (2-Sided) 90%
-7.20 to 5.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 35 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8857
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.57
Confidence Interval (2-Sided) 90%
-5.93 to 7.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 75 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8824
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.57
Confidence Interval (2-Sided) 90%
-6.93 to 5.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-06291874 150 mg
Comments Placebo was the Reference and each of the active doses was the Test for Day 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0192
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.23
Confidence Interval (2-Sided) 90%
2.77 to 15.69
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.90
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percent Change From Baseline in Oxidized LDL
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 33 35 32 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
2.84  (10.730) 2.83  (13.474) 6.54  (17.054) 2.05  (16.179) 11.93  (18.012)
13.Secondary Outcome
Title Percent Change From Baseline in Large LDL Particles
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 32 35 31 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
3.49  (52.827) 33.07  (116.700) -2.40  (28.818) -3.27  (37.299) 21.49  (63.913)
14.Secondary Outcome
Title Percent Change From Baseline in Medium Small LDL Particles
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 32 35 31 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
2.50  (34.138) 8.19  (29.408) 9.90  (35.164) 8.32  (28.865) 14.31  (35.623)
15.Secondary Outcome
Title Percent Change From Baseline in Small LDL Particles
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 32 35 31 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
2.60  (32.581) 7.58  (47.408) 13.21  (42.540) 3.67  (27.883) 13.21  (38.033)
16.Secondary Outcome
Title Percent Change From Baseline in Very Small LDL Particles
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 32 35 31 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
2.87  (33.545) 8.39  (57.323) 14.25  (46.491) 2.61  (28.176) 12.92  (39.082)
17.Secondary Outcome
Title Percent Change From Baseline in Total LDL Particles
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 32 35 31 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
1.33  (16.399) 0.62  (13.142) 3.39  (20.100) 1.95  (17.192) 13.70  (23.707)
18.Secondary Outcome
Title Percent Change From Baseline in LDL Size
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 32 35 31 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
-0.10  (2.294) 0.16  (1.814) -0.19  (1.604) -0.26  (1.803) 0.23  (2.018)
19.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B100
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 33 35 32 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
1.85  (7.912) 2.94  (11.436) 3.82  (13.694) 2.04  (13.900) 10.35  (18.035)
20.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein A
Hide Description 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).
Time Frame Baseline and the mean of Days 28 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 33 35 32 35 33
Mean (Standard Deviation)
Unit of Measure: % (percent change)
-4.38  (16.100) -12.78  (15.095) -13.48  (15.739) -13.17  (16.639) -15.15  (19.449)
21.Secondary Outcome
Title Maximum Plasma Concentration (Cmax)
Hide Description Maximum PF-06291874 plasma concentration.
Time Frame Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 35 31 35 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
714.3
(25%)
1819
(29%)
3560
(28%)
8265
(27%)
22.Secondary Outcome
Title Time to Reach Cmax (Tmax)
Hide Description Time to maximum PF-06291874 plasma concentration.
Time Frame Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 35 31 35 33
Median (Full Range)
Unit of Measure: hour (hr)
6.00
(2.00 to 8.02)
6.00
(2.00 to 8.02)
6.00
(2.00 to 24.0)
6.00
(3.92 to 8.02)
23.Secondary Outcome
Title Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours)
Hide Description Area under the PF-06291874 plasma concentration-time profile from time zero to time tau, the dosing interval, where tau=24 hours.
Time Frame Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 35 31 35 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
12760
(29%)
32370
(32%)
65230
(31%)
142900
(32%)
24.Secondary Outcome
Title Minimum Plasma Concentration (Cmin)
Hide Description Minimum PF-06291874 plasma concentration.
Time Frame Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 35 31 35 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
350.6
(46%)
666.4
(305%)
1257
(361%)
3247
(233%)
25.Secondary Outcome
Title Apparent Clearance (CL/F)
Hide Description Apparent oral clearance of PF-06291874.
Time Frame Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description:
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
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
Overall Number of Participants Analyzed 35 31 35 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/hr
1.176
(29%)
1.082
(32%)
1.150
(31%)
1.050
(32%)
Time Frame From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Hide Arm/Group Description Participants received placebo (three 5/25 milligram [mg] and one 100 mg matching placebo tablets) once daily for 28 days Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days 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 Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days 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
All-Cause Mortality
Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/34 (0.00%)   0/35 (0.00%)   0/34 (0.00%)   1/35 (2.86%)   0/34 (0.00%) 
Nervous system disorders           
Cerebral infarction  1  0/34 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  1/35 (2.86%)  0/34 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo PF-06291874 15 mg PF-06291874 35 mg PF-06291874 75 mg PF-06291874 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/34 (11.76%)   4/35 (11.43%)   8/34 (23.53%)   6/35 (17.14%)   6/34 (17.65%) 
Gastrointestinal disorders           
Diarrhoea  1  1/34 (2.94%)  1/35 (2.86%)  3/34 (8.82%)  1/35 (2.86%)  3/34 (8.82%) 
Nausea  1  0/34 (0.00%)  0/35 (0.00%)  1/34 (2.94%)  0/35 (0.00%)  3/34 (8.82%) 
General disorders           
Fatigue  1  0/34 (0.00%)  2/35 (5.71%)  0/34 (0.00%)  0/35 (0.00%)  0/34 (0.00%) 
Infections and infestations           
Upper respiratory tract infection  1  2/34 (5.88%)  2/35 (5.71%)  3/34 (8.82%)  4/35 (11.43%)  1/34 (2.94%) 
Nervous system disorders           
Headache  1  1/34 (2.94%)  0/35 (0.00%)  3/34 (8.82%)  1/35 (2.86%)  1/34 (2.94%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02175121    
Other Study ID Numbers: B4801011
First Submitted: June 24, 2014
First Posted: June 26, 2014
Results First Submitted: February 19, 2016
Results First Posted: June 15, 2016
Last Update Posted: June 15, 2016