Diabetes Mellitus, Type II
Conditions
Brief summary
This study is going to assess the safety and tolerability of PF-06291874 in adults with Type 2 Diabetes Mellitus as monotherapy, to evaluate the significance of overall glycemic control in these subjects.
Interventions
DRUGPlacebo
Tablet, once daily for 28 days
DRUGPF-06291874
Tablet, 15 mg, once daily for 28 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Baseline up to 10-14 days after last dose of study drug, up to 42 days | 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. |
| Number of Participants With Laboratory Test Abnormalities | Baseline up to 10-14 days after last dose of study drug, up to 42 days | The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests. |
| Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Baseline up to 10-14 days after last dose of study drug, up to 42 days | Vital Signs included seated supine systolic and diastolic blood pressure (BP) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (\<) 90 mm Hg; diastolic BP (DBP) \>=20 mm Hg change from baseline, diastolic \<50 mm Hg; 2), pulse rate \<40 or greater than (\>) 120 beats per minute (bpm). |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | Baseline up to 10-14 days after last dose of study drug, up to 42 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | Baseline, Day 14 and the mean of Days 28 and 29 | 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. |
| Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | Baseline, Day 14 and the mean of Days 28 and 29 | 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. |
| Percent Change From Baseline in Non-HDL-C | Baseline, Day 14 and the mean of Days 28 and 29 | 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. |
| Percent Change From Baseline in Oxidized LDL | Baseline and the mean of Days 28 and 29 | 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). |
| Percent Change From Baseline in Large LDL Particles | Baseline and the mean of Days 28 and 29 | 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). |
| Percent Change From Baseline in Medium Small LDL Particles | Baseline and the mean of Days 28 and 29 | 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). |
| Percent Change From Baseline in Small LDL Particles | Baseline and the mean of Days 28 and 29 | 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). |
| Percent Change From Baseline in Very Small LDL Particles | Baseline and the mean of Days 28 and 29 | 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). |
| Change From Baseline in Mean Daily Glucose | Baseline and Day 28 | 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. |
| Percent Change From Baseline in LDL Size | Baseline and the mean of Days 28 and 29 | 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). |
| Percent Change From Baseline in Apolipoprotein B100 | Baseline and the mean of Days 28 and 29 | 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). |
| Percent Change From Baseline in Lipoprotein A | Baseline and the mean of Days 28 and 29 | 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). |
| Maximum Plasma Concentration (Cmax) | Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) | Maximum PF-06291874 plasma concentration. |
| Time to Reach Cmax (Tmax) | Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) | Time to maximum PF-06291874 plasma concentration. |
| Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours) | Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) | Area under the PF-06291874 plasma concentration-time profile from time zero to time tau, the dosing interval, where tau=24 hours. |
| Minimum Plasma Concentration (Cmin) | Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) | Minimum PF-06291874 plasma concentration. |
| Apparent Clearance (CL/F) | Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) | Apparent oral clearance of PF-06291874. |
| Percent Change From Baseline in Total LDL Particles | Baseline and the mean of Days 28 and 29 | 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). |
| Change From Baseline in Fasting Plasma Glucose | Baseline, Day 14 and the mean of Days 28 and 29 | 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. |
| Percent Change From Baseline in Triglycerides | Baseline, Day 14 and the mean of Days 28 and 29 | 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. |
| Percent Change From Baseline in Total Cholesterol | Baseline, Day 14 and the mean of Days 28 and 29 | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days | 34 |
| 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 | 35 |
| 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 | 34 |
| 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 | 35 |
| 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 | 34 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Personal emergency | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Schedule conflict | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Time issues | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | PF-06291874 15 mg | PF-06291874 35 mg | PF-06291874 75 mg | PF-06291874 150 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 6.3 | 56.1 years STANDARD_DEVIATION 9 | 57.8 years STANDARD_DEVIATION 7.5 | 55.5 years STANDARD_DEVIATION 7.6 | 55.2 years STANDARD_DEVIATION 7.5 | 56.7 years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 16 Participants | 9 Participants | 16 Participants | 12 Participants | 18 Participants | 71 Participants |
| Sex: Female, Male Male | 18 Participants | 26 Participants | 18 Participants | 23 Participants | 16 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 34 | 4 / 35 | 8 / 34 | 6 / 35 | 6 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 35 | 0 / 34 | 1 / 35 | 0 / 34 |
Outcome results
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).
Time frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
Population: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine DBP <50 mm Hg | 1 participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine SBP >= 30 mm Hg | 1 participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine DBP >=20 mm Hg | 1 participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate >120 bpm | 0 participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate <40 bpm | 0 participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine DBP >=20 mm Hg | 3 participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine SBP <90 mm Hg | 3 participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine SBP >=30 mm Hg | 3 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine SBP >= 30 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine SBP >=30 mm Hg | 3 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine DBP >=20 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine DBP >=20 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate <40 bpm | 0 participants |
| PF-06291874 15 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate >120 bpm | 0 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate <40 bpm | 0 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate >120 bpm | 0 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine DBP >=20 mm Hg | 0 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine SBP >=30 mm Hg | 3 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine SBP >= 30 mm Hg | 0 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine DBP >=20 mm Hg | 2 participants |
| PF-06291874 35 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine DBP >=20 mm Hg | 1 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate <40 bpm | 0 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine DBP >=20 mm Hg | 0 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine SBP >= 30 mm Hg | 0 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine SBP >=30 mm Hg | 1 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 75 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate >120 bpm | 0 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine SBP >=30 mm Hg | 6 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Increase: supine DBP >=20 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine SBP >= 30 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Decrease: supine DBP >=20 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate <40 bpm | 0 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern | Pulse rate >120 bpm | 0 participants |
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.
Time frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
Population: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 450-480 msec | 2 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase >=60 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval >=300 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval >=140 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 480-500 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval >=500 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval increase >=25%/50% | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval increase >=50% | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase 30-60 msec | 1 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval >=500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval >=140 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval >=300 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval increase >=25%/50% | 1 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase 30-60 msec | 5 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 450-480 msec | 4 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase >=60 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval increase >=50% | 0 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval >=500 msec | 0 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase >=60 msec | 1 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval >=300 msec | 0 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 480-500 msec | 1 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase 30-60 msec | 4 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval >=140 msec | 0 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval increase >=50% | 0 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval increase >=25%/50% | 0 participants |
| PF-06291874 35 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 450-480 msec | 4 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase 30-60 msec | 4 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval increase >=25%/50% | 0 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase >=60 msec | 0 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval >=300 msec | 0 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval >=140 msec | 0 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 450-480 msec | 2 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval >=500 msec | 0 participants |
| PF-06291874 75 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval increase >=50% | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval >=140 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 450-480 msec | 3 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval >=300 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval 480-500 msec | 1 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | PR interval increase >=25%/50% | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase >=60 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval increase 30-60 msec | 5 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QRS interval increase >=50% | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern | QTcF interval >=500 msec | 0 participants |
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.
Time frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
Population: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities | 31 participants |
| PF-06291874 15 mg | Number of Participants With Laboratory Test Abnormalities | 31 participants |
| PF-06291874 35 mg | Number of Participants With Laboratory Test Abnormalities | 24 participants |
| PF-06291874 75 mg | Number of Participants With Laboratory Test Abnormalities | 32 participants |
| PF-06291874 150 mg | Number of Participants With Laboratory Test Abnormalities | 30 participants |
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.
Time frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
Population: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), or Serious Adverse Events (SAEs), or Hypoglycemic Adverse Events (HAE) or Withdrawals Due to Adverse Events (AEs) | Number of Participants with SAEs | 0 participants |
| Placebo | 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) | Number of Participants discontinued from study | 1 participants |
| Placebo | 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) | Number of Participants With AEs | 11 participants |
| Placebo | 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) | Number of Participants with Protocol-Defined HAEs | 0 participants |
| PF-06291874 15 mg | 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) | Number of Participants With AEs | 7 participants |
| PF-06291874 15 mg | 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) | Number of Participants with SAEs | 0 participants |
| PF-06291874 15 mg | 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) | Number of Participants discontinued from study | 1 participants |
| PF-06291874 15 mg | 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) | Number of Participants with Protocol-Defined HAEs | 0 participants |
| PF-06291874 35 mg | 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) | Number of Participants with Protocol-Defined HAEs | 0 participants |
| PF-06291874 35 mg | 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) | Number of Participants discontinued from study | 2 participants |
| PF-06291874 35 mg | 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) | Number of Participants with SAEs | 0 participants |
| PF-06291874 35 mg | 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) | Number of Participants With AEs | 10 participants |
| PF-06291874 75 mg | 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) | Number of Participants discontinued from study | 1 participants |
| PF-06291874 75 mg | 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) | Number of Participants With AEs | 11 participants |
| PF-06291874 75 mg | 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) | Number of Participants with SAEs | 1 participants |
| PF-06291874 75 mg | 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) | Number of Participants with Protocol-Defined HAEs | 1 participants |
| PF-06291874 150 mg | 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) | Number of Participants discontinued from study | 1 participants |
| PF-06291874 150 mg | 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) | Number of Participants with Protocol-Defined HAEs | 0 participants |
| PF-06291874 150 mg | 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) | Number of Participants with SAEs | 0 participants |
| PF-06291874 150 mg | 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) | Number of Participants With AEs | 12 participants |
Secondary
Apparent Clearance (CL/F)
Apparent oral clearance of PF-06291874.
Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Clearance (CL/F) | 1.176 L/hr | Geometric Coefficient of Variation 29 |
| PF-06291874 15 mg | Apparent Clearance (CL/F) | 1.082 L/hr | Geometric Coefficient of Variation 32 |
| PF-06291874 35 mg | Apparent Clearance (CL/F) | 1.150 L/hr | Geometric Coefficient of Variation 31 |
| PF-06291874 75 mg | Apparent Clearance (CL/F) | 1.050 L/hr | Geometric Coefficient of Variation 32 |
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.
Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours) | 12760 ng*hr/mL | Geometric Coefficient of Variation 29 |
| PF-06291874 15 mg | Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours) | 32370 ng*hr/mL | Geometric Coefficient of Variation 32 |
| PF-06291874 35 mg | Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours) | 65230 ng*hr/mL | Geometric Coefficient of Variation 31 |
| PF-06291874 75 mg | Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours) | 142900 ng*hr/mL | Geometric Coefficient of Variation 32 |
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.
Time frame: Baseline, Day 14 and the mean of Days 28 and 29
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose | Day 14 Change from Baseline (N=33,34,32,35,33) | -6.08 mg/dL | Standard Deviation 29.778 |
| Placebo | Change From Baseline in Fasting Plasma Glucose | Day 28 Change from Baseline (N=33,35,32,35,33) | 6.11 mg/dL | Standard Deviation 29.84 |
| PF-06291874 15 mg | Change From Baseline in Fasting Plasma Glucose | Day 14 Change from Baseline (N=33,34,32,35,33) | -21.76 mg/dL | Standard Deviation 24.278 |
| PF-06291874 15 mg | Change From Baseline in Fasting Plasma Glucose | Day 28 Change from Baseline (N=33,35,32,35,33) | -20.26 mg/dL | Standard Deviation 23.523 |
| PF-06291874 35 mg | Change From Baseline in Fasting Plasma Glucose | Day 14 Change from Baseline (N=33,34,32,35,33) | -29.59 mg/dL | Standard Deviation 31.552 |
| PF-06291874 35 mg | Change From Baseline in Fasting Plasma Glucose | Day 28 Change from Baseline (N=33,35,32,35,33) | -26.61 mg/dL | Standard Deviation 22.045 |
| PF-06291874 75 mg | Change From Baseline in Fasting Plasma Glucose | Day 28 Change from Baseline (N=33,35,32,35,33) | -45.27 mg/dL | Standard Deviation 22.115 |
| PF-06291874 75 mg | Change From Baseline in Fasting Plasma Glucose | Day 14 Change from Baseline (N=33,34,32,35,33) | -45.59 mg/dL | Standard Deviation 26.04 |
| PF-06291874 150 mg | Change From Baseline in Fasting Plasma Glucose | Day 14 Change from Baseline (N=33,34,32,35,33) | -52.18 mg/dL | Standard Deviation 30.824 |
| PF-06291874 150 mg | Change From Baseline in Fasting Plasma Glucose | Day 28 Change from Baseline (N=33,35,32,35,33) | -50.45 mg/dL | Standard Deviation 32.045 |
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.00690% CI: [-25.9, -6.6]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: <0.000190% CI: [-36.81, -17.15]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: <0.000190% CI: [-49.2, -30]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: <0.000190% CI: [-56.46, -36.98]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: <0.000190% CI: [-35.89, -18.25]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: <0.000190% CI: [-45.21, -27.14]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: <0.000190% CI: [-60.29, -42.65]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: <0.000190% CI: [-66.12, -48.22]Mixed Models Analysis
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.
Time frame: Baseline and Day 28
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Daily Glucose | 6.63 mg/dL | Standard Deviation 38.938 |
| PF-06291874 15 mg | Change From Baseline in Mean Daily Glucose | -29.15 mg/dL | Standard Deviation 25.659 |
| PF-06291874 35 mg | Change From Baseline in Mean Daily Glucose | -32.29 mg/dL | Standard Deviation 29.572 |
| PF-06291874 75 mg | Change From Baseline in Mean Daily Glucose | -59.98 mg/dL | Standard Deviation 29.363 |
| PF-06291874 150 mg | Change From Baseline in Mean Daily Glucose | -55.99 mg/dL | Standard Deviation 39.798 |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: <0.000190% CI: [-51.49, -29.16]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: <0.000190% CI: [-57.08, -33.99]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: <0.000190% CI: [-79.92, -57.65]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: <0.000190% CI: [-79.46, -56.78]ANCOVA
Secondary
Maximum Plasma Concentration (Cmax)
Maximum PF-06291874 plasma concentration.
Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) | 714.3 ng/mL | Geometric Coefficient of Variation 25 |
| PF-06291874 15 mg | Maximum Plasma Concentration (Cmax) | 1819 ng/mL | Geometric Coefficient of Variation 29 |
| PF-06291874 35 mg | Maximum Plasma Concentration (Cmax) | 3560 ng/mL | Geometric Coefficient of Variation 28 |
| PF-06291874 75 mg | Maximum Plasma Concentration (Cmax) | 8265 ng/mL | Geometric Coefficient of Variation 27 |
Secondary
Minimum Plasma Concentration (Cmin)
Minimum PF-06291874 plasma concentration.
Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Minimum Plasma Concentration (Cmin) | 350.6 ng/mL | Geometric Coefficient of Variation 46 |
| PF-06291874 15 mg | Minimum Plasma Concentration (Cmin) | 666.4 ng/mL | Geometric Coefficient of Variation 305 |
| PF-06291874 35 mg | Minimum Plasma Concentration (Cmin) | 1257 ng/mL | Geometric Coefficient of Variation 361 |
| PF-06291874 75 mg | Minimum Plasma Concentration (Cmin) | 3247 ng/mL | Geometric Coefficient of Variation 233 |
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein B100 | 1.85 % (percent change) | Standard Deviation 7.912 |
| PF-06291874 15 mg | Percent Change From Baseline in Apolipoprotein B100 | 2.94 % (percent change) | Standard Deviation 11.436 |
| PF-06291874 35 mg | Percent Change From Baseline in Apolipoprotein B100 | 3.82 % (percent change) | Standard Deviation 13.694 |
| PF-06291874 75 mg | Percent Change From Baseline in Apolipoprotein B100 | 2.04 % (percent change) | Standard Deviation 13.9 |
| PF-06291874 150 mg | Percent Change From Baseline in Apolipoprotein B100 | 10.35 % (percent change) | Standard Deviation 18.035 |
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.
Time frame: Baseline, Day 14 and the mean of Days 28 and 29
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 6.99 % (percent change) | Standard Deviation 15.59 |
| Placebo | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 3.94 % (percent change) | Standard Deviation 11.33 |
| PF-06291874 15 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 9.02 % (percent change) | Standard Deviation 14.884 |
| PF-06291874 15 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 4.78 % (percent change) | Standard Deviation 9.271 |
| PF-06291874 35 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 11.27 % (percent change) | Standard Deviation 15.72 |
| PF-06291874 35 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 4.82 % (percent change) | Standard Deviation 13.426 |
| PF-06291874 75 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 8.34 % (percent change) | Standard Deviation 9.013 |
| PF-06291874 75 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 14.47 % (percent change) | Standard Deviation 16.884 |
| PF-06291874 150 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 19.75 % (percent change) | Standard Deviation 18.172 |
| PF-06291874 150 mg | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 18.73 % (percent change) | Standard Deviation 24.979 |
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.204190% CI: [-1.36, 10.48]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.655390% CI: [-4.78, 8.33]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.256990% CI: [-2.09, 11.3]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.055390% CI: [1.09, 14.18]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.001690% CI: [6.26, 19.53]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.871790% CI: [-5.35, 6.51]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.74390% CI: [-4.86, 7.26]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: <0.000190% CI: [8.92, 20.92]Mixed Models Analysis
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Large LDL Particles | 3.49 % (percent change) | Standard Deviation 52.827 |
| PF-06291874 15 mg | Percent Change From Baseline in Large LDL Particles | 33.07 % (percent change) | Standard Deviation 116.7 |
| PF-06291874 35 mg | Percent Change From Baseline in Large LDL Particles | -2.40 % (percent change) | Standard Deviation 28.818 |
| PF-06291874 75 mg | Percent Change From Baseline in Large LDL Particles | -3.27 % (percent change) | Standard Deviation 37.299 |
| PF-06291874 150 mg | Percent Change From Baseline in Large LDL Particles | 21.49 % (percent change) | Standard Deviation 63.913 |
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in LDL Size | -0.10 % (percent change) | Standard Deviation 2.294 |
| PF-06291874 15 mg | Percent Change From Baseline in LDL Size | 0.16 % (percent change) | Standard Deviation 1.814 |
| PF-06291874 35 mg | Percent Change From Baseline in LDL Size | -0.19 % (percent change) | Standard Deviation 1.604 |
| PF-06291874 75 mg | Percent Change From Baseline in LDL Size | -0.26 % (percent change) | Standard Deviation 1.803 |
| PF-06291874 150 mg | Percent Change From Baseline in LDL Size | 0.23 % (percent change) | Standard Deviation 2.018 |
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipoprotein A | -4.38 % (percent change) | Standard Deviation 16.1 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipoprotein A | -12.78 % (percent change) | Standard Deviation 15.095 |
| PF-06291874 35 mg | Percent Change From Baseline in Lipoprotein A | -13.48 % (percent change) | Standard Deviation 15.739 |
| PF-06291874 75 mg | Percent Change From Baseline in Lipoprotein A | -13.17 % (percent change) | Standard Deviation 16.639 |
| PF-06291874 150 mg | Percent Change From Baseline in Lipoprotein A | -15.15 % (percent change) | Standard Deviation 19.449 |
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.
Time frame: Baseline, Day 14 and the mean of Days 28 and 29
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 6.24 % (percent change) | Standard Deviation 15.803 |
| Placebo | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 2.92 % (percent change) | Standard Deviation 12.046 |
| PF-06291874 15 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 2.46 % (percent change) | Standard Deviation 13.472 |
| PF-06291874 15 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 3.95 % (percent change) | Standard Deviation 14.407 |
| PF-06291874 35 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 3.51 % (percent change) | Standard Deviation 19.507 |
| PF-06291874 35 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 8.12 % (percent change) | Standard Deviation 23.085 |
| PF-06291874 75 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 2.15 % (percent change) | Standard Deviation 17.238 |
| PF-06291874 75 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 5.29 % (percent change) | Standard Deviation 15.223 |
| PF-06291874 150 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D28 Percent Change from Baseline(N=33,35,32,35,33) | 14.19 % (percent change) | Standard Deviation 24.128 |
| PF-06291874 150 mg | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) | D14 Percent Change from Baseline(N=33,35,32,35,33) | 14.24 % (percent change) | Standard Deviation 21.612 |
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.618290% CI: [-9.15, 4.91]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.702890% CI: [-5.52, 8.84]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.944590% CI: [-7.33, 6.73]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.037390% CI: [1.93, 16.21]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.944890% CI: [-7.25, 6.67]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.931290% CI: [-6.74, 7.49]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.979190% CI: [-7.07, 6.85]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.004490% CI: [5.26, 19.41]Mixed Models Analysis
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Medium Small LDL Particles | 2.50 % (percent change) | Standard Deviation 34.138 |
| PF-06291874 15 mg | Percent Change From Baseline in Medium Small LDL Particles | 8.19 % (percent change) | Standard Deviation 29.408 |
| PF-06291874 35 mg | Percent Change From Baseline in Medium Small LDL Particles | 9.90 % (percent change) | Standard Deviation 35.164 |
| PF-06291874 75 mg | Percent Change From Baseline in Medium Small LDL Particles | 8.32 % (percent change) | Standard Deviation 28.865 |
| PF-06291874 150 mg | Percent Change From Baseline in Medium Small LDL Particles | 14.31 % (percent change) | Standard Deviation 35.623 |
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.
Time frame: Baseline, Day 14 and the mean of Days 28 and 29
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Non-HDL-C | D28 Percent Change from Baseline(N=33,35,32,35,33) | 3.84 % (percent change) | Standard Deviation 8.728 |
| Placebo | Percent Change From Baseline in Non-HDL-C | D14 Percent Change from Baseline(N=33,35,32,35,33) | 3.29 % (percent change) | Standard Deviation 11.686 |
| PF-06291874 15 mg | Percent Change From Baseline in Non-HDL-C | D14 Percent Change from Baseline(N=33,35,32,35,33) | 2.96 % (percent change) | Standard Deviation 14.179 |
| PF-06291874 15 mg | Percent Change From Baseline in Non-HDL-C | D28 Percent Change from Baseline(N=33,35,32,35,33) | 2.55 % (percent change) | Standard Deviation 14.319 |
| PF-06291874 35 mg | Percent Change From Baseline in Non-HDL-C | D28 Percent Change from Baseline(N=33,35,32,35,33) | 4.65 % (percent change) | Standard Deviation 14.309 |
| PF-06291874 35 mg | Percent Change From Baseline in Non-HDL-C | D14 Percent Change from Baseline(N=33,35,32,35,33) | 7.52 % (percent change) | Standard Deviation 20.983 |
| PF-06291874 75 mg | Percent Change From Baseline in Non-HDL-C | D14 Percent Change from Baseline(N=33,35,32,35,33) | 1.26 % (percent change) | Standard Deviation 16.181 |
| PF-06291874 75 mg | Percent Change From Baseline in Non-HDL-C | D28 Percent Change from Baseline(N=33,35,32,35,33) | 2.75 % (percent change) | Standard Deviation 17.275 |
| PF-06291874 150 mg | Percent Change From Baseline in Non-HDL-C | D14 Percent Change from Baseline(N=33,35,32,35,33) | 12.32 % (percent change) | Standard Deviation 22.192 |
| PF-06291874 150 mg | Percent Change From Baseline in Non-HDL-C | D28 Percent Change from Baseline(N=33,35,32,35,33) | 12.32 % (percent change) | Standard Deviation 22.758 |
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.97590% CI: [-6.62, 6.87]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.339690% CI: [-2.9, 10.87]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.714290% CI: [-8.23, 5.24]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.019290% CI: [2.94, 16.63]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.827790% CI: [-7.2, 5.52]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.885790% CI: [-5.93, 7.06]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.882490% CI: [-6.93, 5.79]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.019290% CI: [2.77, 15.69]Mixed Models Analysis
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Oxidized LDL | 2.84 % (percent change) | Standard Deviation 10.73 |
| PF-06291874 15 mg | Percent Change From Baseline in Oxidized LDL | 2.83 % (percent change) | Standard Deviation 13.474 |
| PF-06291874 35 mg | Percent Change From Baseline in Oxidized LDL | 6.54 % (percent change) | Standard Deviation 17.054 |
| PF-06291874 75 mg | Percent Change From Baseline in Oxidized LDL | 2.05 % (percent change) | Standard Deviation 16.179 |
| PF-06291874 150 mg | Percent Change From Baseline in Oxidized LDL | 11.93 % (percent change) | Standard Deviation 18.012 |
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Small LDL Particles | 2.60 % (percent change) | Standard Deviation 32.581 |
| PF-06291874 15 mg | Percent Change From Baseline in Small LDL Particles | 7.58 % (percent change) | Standard Deviation 47.408 |
| PF-06291874 35 mg | Percent Change From Baseline in Small LDL Particles | 13.21 % (percent change) | Standard Deviation 42.54 |
| PF-06291874 75 mg | Percent Change From Baseline in Small LDL Particles | 3.67 % (percent change) | Standard Deviation 27.883 |
| PF-06291874 150 mg | Percent Change From Baseline in Small LDL Particles | 13.21 % (percent change) | Standard Deviation 38.033 |
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.
Time frame: Baseline, Day 14 and the mean of Days 28 and 29
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Cholesterol | D28 Percent Change from Baseline(N=33,35,32,35,33) | 4.07 % (percent change) | Standard Deviation 7.928 |
| Placebo | Percent Change From Baseline in Total Cholesterol | D14 Percent Change from Baseline(N=33,35,32,35,33) | 4.04 % (percent change) | Standard Deviation 11.024 |
| PF-06291874 15 mg | Percent Change From Baseline in Total Cholesterol | D14 Percent Change from Baseline(N=33,35,32,35,33) | 4.49 % (percent change) | Standard Deviation 11.036 |
| PF-06291874 15 mg | Percent Change From Baseline in Total Cholesterol | D28 Percent Change from Baseline(N=33,35,32,35,33) | 2.93 % (percent change) | Standard Deviation 11.503 |
| PF-06291874 35 mg | Percent Change From Baseline in Total Cholesterol | D28 Percent Change from Baseline(N=33,35,32,35,33) | 4.52 % (percent change) | Standard Deviation 11.354 |
| PF-06291874 35 mg | Percent Change From Baseline in Total Cholesterol | D14 Percent Change from Baseline(N=33,35,32,35,33) | 7.94 % (percent change) | Standard Deviation 16.059 |
| PF-06291874 75 mg | Percent Change From Baseline in Total Cholesterol | D28 Percent Change from Baseline(N=33,35,32,35,33) | 4.05 % (percent change) | Standard Deviation 13.061 |
| PF-06291874 75 mg | Percent Change From Baseline in Total Cholesterol | D14 Percent Change from Baseline(N=33,35,32,35,33) | 4.60 % (percent change) | Standard Deviation 12.888 |
| PF-06291874 150 mg | Percent Change From Baseline in Total Cholesterol | D14 Percent Change from Baseline(N=33,35,32,35,33) | 12.98 % (percent change) | Standard Deviation 17.177 |
| PF-06291874 150 mg | Percent Change From Baseline in Total Cholesterol | D28 Percent Change from Baseline(N=33,35,32,35,33) | 12.86 % (percent change) | Standard Deviation 17.086 |
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.851690% CI: [-4.73, 5.93]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.230390% CI: [-1.48, 9.42]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.713290% CI: [-4.15, 6.52]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.003490% CI: [4.32, 15.16]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.739490% CI: [-5.89, 3.92]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.865290% CI: [-4.5, 5.53]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.83790% CI: [-4.3, 5.52]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.001890% CI: [4.6, 14.58]Mixed Models Analysis
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Total LDL Particles | 1.33 % (percent change) | Standard Deviation 16.399 |
| PF-06291874 15 mg | Percent Change From Baseline in Total LDL Particles | 0.62 % (percent change) | Standard Deviation 13.142 |
| PF-06291874 35 mg | Percent Change From Baseline in Total LDL Particles | 3.39 % (percent change) | Standard Deviation 20.1 |
| PF-06291874 75 mg | Percent Change From Baseline in Total LDL Particles | 1.95 % (percent change) | Standard Deviation 17.192 |
| PF-06291874 150 mg | Percent Change From Baseline in Total LDL Particles | 13.70 % (percent change) | Standard Deviation 23.707 |
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.
Time frame: Baseline, Day 14 and the mean of Days 28 and 29
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Triglycerides | D14 Percent Change from Baseline(N=33,35,32,35,33) | 0.52 % (percent change) | Standard Deviation 47.749 |
| Placebo | Percent Change From Baseline in Triglycerides | D28 Percent Change from Baseline(N=33,35,32,35,33） | 19.58 % (percent change) | Standard Deviation 26.037 |
| PF-06291874 15 mg | Percent Change From Baseline in Triglycerides | D28 Percent Change from Baseline(N=33,35,32,35,33） | 15.20 % (percent change) | Standard Deviation 29.122 |
| PF-06291874 15 mg | Percent Change From Baseline in Triglycerides | D14 Percent Change from Baseline(N=33,35,32,35,33) | 25.69 % (percent change) | Standard Deviation 93.991 |
| PF-06291874 35 mg | Percent Change From Baseline in Triglycerides | D14 Percent Change from Baseline(N=33,35,32,35,33) | 26.95 % (percent change) | Standard Deviation 100.972 |
| PF-06291874 35 mg | Percent Change From Baseline in Triglycerides | D28 Percent Change from Baseline(N=33,35,32,35,33） | 19.48 % (percent change) | Standard Deviation 28.647 |
| PF-06291874 75 mg | Percent Change From Baseline in Triglycerides | D28 Percent Change from Baseline(N=33,35,32,35,33） | 20.72 % (percent change) | Standard Deviation 40.626 |
| PF-06291874 75 mg | Percent Change From Baseline in Triglycerides | D14 Percent Change from Baseline(N=33,35,32,35,33) | 2.71 % (percent change) | Standard Deviation 63.99 |
| PF-06291874 150 mg | Percent Change From Baseline in Triglycerides | D14 Percent Change from Baseline(N=33,35,32,35,33) | 21.52 % (percent change) | Standard Deviation 86.951 |
| PF-06291874 150 mg | Percent Change From Baseline in Triglycerides | D28 Percent Change from Baseline(N=33,35,32,35,33） | 24.96 % (percent change) | Standard Deviation 35.09 |
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.206390% CI: [-3.91, 29.62]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.208790% CI: [-4.05, 30.11]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.580290% CI: [-11.11, 22.3]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 14.p-value: 0.155390% CI: [-2.32, 31.59]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.774190% CI: [-14.87, 10.47]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.958890% CI: [-13.28, 12.47]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.852390% CI: [-11.17, 14.01]Mixed Models Analysis
Comparison: Placebo was the Reference and each of the active doses was the Test for Day 28.p-value: 0.416690% CI: [-6.49, 19.08]Mixed Models Analysis
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).
Time frame: Baseline and the mean of Days 28 and 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Very Small LDL Particles | 2.87 % (percent change) | Standard Deviation 33.545 |
| PF-06291874 15 mg | Percent Change From Baseline in Very Small LDL Particles | 8.39 % (percent change) | Standard Deviation 57.323 |
| PF-06291874 35 mg | Percent Change From Baseline in Very Small LDL Particles | 14.25 % (percent change) | Standard Deviation 46.491 |
| PF-06291874 75 mg | Percent Change From Baseline in Very Small LDL Particles | 2.61 % (percent change) | Standard Deviation 28.176 |
| PF-06291874 150 mg | Percent Change From Baseline in Very Small LDL Particles | 12.92 % (percent change) | Standard Deviation 39.082 |
Secondary
Time to Reach Cmax (Tmax)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Cmax (Tmax) | 6.00 hour (hr) |
| PF-06291874 15 mg | Time to Reach Cmax (Tmax) | 6.00 hour (hr) |
| PF-06291874 35 mg | Time to Reach Cmax (Tmax) | 6.00 hour (hr) |
| PF-06291874 75 mg | Time to Reach Cmax (Tmax) | 6.00 hour (hr) |