Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06291874 As Oral Monotherapy To Treat Adults With Type 2 Diabetes Mellitus (NCT NCT02175121)
NCT ID: NCT02175121
Last Updated: 2016-06-15
Results Overview
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.
COMPLETED
PHASE2
172 participants
Baseline up to 10-14 days after last dose of study drug, up to 42 days
2016-06-15
Participant Flow
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.
Participant milestones
| Measure |
Placebo
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
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
|
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
|
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
|
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
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
34
|
35
|
34
|
35
|
34
|
|
Overall Study
COMPLETED
|
33
|
34
|
32
|
34
|
33
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
2
|
1
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
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
|
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
|
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
|
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
|
|---|---|---|---|---|---|
|
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
Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06291874 As Oral Monotherapy To Treat Adults With Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 150 mg
n=34 Participants
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
n=172 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
58.9 years
STANDARD_DEVIATION 6.3 • n=5 Participants
|
56.1 years
STANDARD_DEVIATION 9 • n=7 Participants
|
57.8 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
55.5 years
STANDARD_DEVIATION 7.6 • n=4 Participants
|
55.2 years
STANDARD_DEVIATION 7.5 • n=21 Participants
|
56.7 years
STANDARD_DEVIATION 7.7 • n=10 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
71 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
101 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 10-14 days after last dose of study drug, up to 42 daysPopulation: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
11 participants
|
7 participants
|
10 participants
|
11 participants
|
|
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
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
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
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
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
|
1 participants
|
1 participants
|
2 participants
|
1 participants
|
PRIMARY outcome
Timeframe: Baseline up to 10-14 days after last dose of study drug, up to 42 daysPopulation: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities
|
30 participants
|
31 participants
|
31 participants
|
24 participants
|
32 participants
|
PRIMARY outcome
Timeframe: Baseline up to 10-14 days after last dose of study drug, up to 42 daysPopulation: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
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
|
3 participants
|
0 participants
|
0 participants
|
0 participants
|
|
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
|
3 participants
|
3 participants
|
3 participants
|
1 participants
|
|
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
|
1 participants
|
0 participants
|
2 participants
|
1 participants
|
|
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
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
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
|
3 participants
|
0 participants
|
0 participants
|
0 participants
|
|
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
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
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
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Baseline up to 10-14 days after last dose of study drug, up to 42 daysPopulation: The safety analysis set was defined as all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
PR interval >=300 msec
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
QRS interval >=140 msec
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
QTcF interval 450-480 msec
|
3 participants
|
2 participants
|
4 participants
|
4 participants
|
2 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
QTcF interval 480-500 msec
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
QTcF interval >=500 msec
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
PR interval increase >=25%/50%
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
QRS interval increase >=50%
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
QTcF interval increase 30-60 msec
|
5 participants
|
1 participants
|
5 participants
|
4 participants
|
4 participants
|
|
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
QTcF interval increase >=60 msec
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and Day 28Population: 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.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=33 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=31 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Change From Baseline in Mean Daily Glucose
|
-55.99 mg/dL
Standard Deviation 39.798 • Interval -65.76 to -49.78
|
6.63 mg/dL
Standard Deviation 38.938 • Interval 2.33 to 18.37
|
-29.15 mg/dL
Standard Deviation 25.659 • Interval -37.73 to -22.22
|
-32.29 mg/dL
Standard Deviation 29.572 • Interval -43.44 to -26.93
|
-59.98 mg/dL
Standard Deviation 29.363 • Interval -66.19 to -50.68
|
SECONDARY outcome
Timeframe: Baseline, Day 14 and the mean of Days 28 and 29Population: 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.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
-6.08 mg/dL
Standard Deviation 29.778
|
-21.76 mg/dL
Standard Deviation 24.278
|
-29.59 mg/dL
Standard Deviation 31.552
|
-45.59 mg/dL
Standard Deviation 26.040
|
|
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
|
6.11 mg/dL
Standard Deviation 29.840
|
-20.26 mg/dL
Standard Deviation 23.523
|
-26.61 mg/dL
Standard Deviation 22.045
|
-45.27 mg/dL
Standard Deviation 22.115
|
SECONDARY outcome
Timeframe: Baseline, Day 14 and the mean of Days 28 and 29Population: 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.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
0.52 % (percent change)
Standard Deviation 47.749
|
25.69 % (percent change)
Standard Deviation 93.991
|
26.95 % (percent change)
Standard Deviation 100.972
|
2.71 % (percent change)
Standard Deviation 63.990
|
|
Percent Change From Baseline in Triglycerides
D28 Percent Change from Baseline(N=33,35,32,35,33）
|
24.96 % (percent change)
Standard Deviation 35.090
|
19.58 % (percent change)
Standard Deviation 26.037
|
15.20 % (percent change)
Standard Deviation 29.122
|
19.48 % (percent change)
Standard Deviation 28.647
|
20.72 % (percent change)
Standard Deviation 40.626
|
SECONDARY outcome
Timeframe: Baseline, Day 14 and the mean of Days 28 and 29Population: 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.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
4.07 % (percent change)
Standard Deviation 7.928
|
2.93 % (percent change)
Standard Deviation 11.503
|
4.52 % (percent change)
Standard Deviation 11.354
|
4.05 % (percent change)
Standard Deviation 13.061
|
|
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
|
4.04 % (percent change)
Standard Deviation 11.024
|
4.49 % (percent change)
Standard Deviation 11.036
|
7.94 % (percent change)
Standard Deviation 16.059
|
4.60 % (percent change)
Standard Deviation 12.888
|
SECONDARY outcome
Timeframe: Baseline, Day 14 and the mean of Days 28 and 29Population: 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.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
6.24 % (percent change)
Standard Deviation 15.803
|
3.95 % (percent change)
Standard Deviation 14.407
|
8.12 % (percent change)
Standard Deviation 23.085
|
5.29 % (percent change)
Standard Deviation 15.223
|
|
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
|
2.92 % (percent change)
Standard Deviation 12.046
|
2.46 % (percent change)
Standard Deviation 13.472
|
3.51 % (percent change)
Standard Deviation 19.507
|
2.15 % (percent change)
Standard Deviation 17.238
|
SECONDARY outcome
Timeframe: Baseline, Day 14 and the mean of Days 28 and 29Population: 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.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
3.94 % (percent change)
Standard Deviation 11.330
|
4.78 % (percent change)
Standard Deviation 9.271
|
4.82 % (percent change)
Standard Deviation 13.426
|
8.34 % (percent change)
Standard Deviation 9.013
|
|
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
|
6.99 % (percent change)
Standard Deviation 15.590
|
9.02 % (percent change)
Standard Deviation 14.884
|
11.27 % (percent change)
Standard Deviation 15.720
|
14.47 % (percent change)
Standard Deviation 16.884
|
SECONDARY outcome
Timeframe: Baseline, Day 14 and the mean of Days 28 and 29Population: 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.
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.
Outcome measures
| Measure |
PF-06291874 150 mg
n=34 Participants
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
|
Placebo
n=34 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
3.29 % (percent change)
Standard Deviation 11.686
|
2.96 % (percent change)
Standard Deviation 14.179
|
7.52 % (percent change)
Standard Deviation 20.983
|
1.26 % (percent change)
Standard Deviation 16.181
|
|
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
|
3.84 % (percent change)
Standard Deviation 8.728
|
2.55 % (percent change)
Standard Deviation 14.319
|
4.65 % (percent change)
Standard Deviation 14.309
|
2.75 % (percent change)
Standard Deviation 17.275
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=33 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=32 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Oxidized LDL
|
11.93 % (percent change)
Standard Deviation 18.012
|
2.84 % (percent change)
Standard Deviation 10.730
|
2.83 % (percent change)
Standard Deviation 13.474
|
6.54 % (percent change)
Standard Deviation 17.054
|
2.05 % (percent change)
Standard Deviation 16.179
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=32 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=31 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Large LDL Particles
|
21.49 % (percent change)
Standard Deviation 63.913
|
3.49 % (percent change)
Standard Deviation 52.827
|
33.07 % (percent change)
Standard Deviation 116.700
|
-2.40 % (percent change)
Standard Deviation 28.818
|
-3.27 % (percent change)
Standard Deviation 37.299
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=32 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=31 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Medium Small LDL Particles
|
14.31 % (percent change)
Standard Deviation 35.623
|
2.50 % (percent change)
Standard Deviation 34.138
|
8.19 % (percent change)
Standard Deviation 29.408
|
9.90 % (percent change)
Standard Deviation 35.164
|
8.32 % (percent change)
Standard Deviation 28.865
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=32 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=31 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Small LDL Particles
|
13.21 % (percent change)
Standard Deviation 38.033
|
2.60 % (percent change)
Standard Deviation 32.581
|
7.58 % (percent change)
Standard Deviation 47.408
|
13.21 % (percent change)
Standard Deviation 42.540
|
3.67 % (percent change)
Standard Deviation 27.883
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=32 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=31 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Very Small LDL Particles
|
12.92 % (percent change)
Standard Deviation 39.082
|
2.87 % (percent change)
Standard Deviation 33.545
|
8.39 % (percent change)
Standard Deviation 57.323
|
14.25 % (percent change)
Standard Deviation 46.491
|
2.61 % (percent change)
Standard Deviation 28.176
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=32 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=31 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Total LDL Particles
|
13.70 % (percent change)
Standard Deviation 23.707
|
1.33 % (percent change)
Standard Deviation 16.399
|
0.62 % (percent change)
Standard Deviation 13.142
|
3.39 % (percent change)
Standard Deviation 20.100
|
1.95 % (percent change)
Standard Deviation 17.192
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=32 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=31 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in LDL Size
|
0.23 % (percent change)
Standard Deviation 2.018
|
-0.10 % (percent change)
Standard Deviation 2.294
|
0.16 % (percent change)
Standard Deviation 1.814
|
-0.19 % (percent change)
Standard Deviation 1.604
|
-0.26 % (percent change)
Standard Deviation 1.803
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=33 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=32 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B100
|
10.35 % (percent change)
Standard Deviation 18.035
|
1.85 % (percent change)
Standard Deviation 7.912
|
2.94 % (percent change)
Standard Deviation 11.436
|
3.82 % (percent change)
Standard Deviation 13.694
|
2.04 % (percent change)
Standard Deviation 13.900
|
SECONDARY outcome
Timeframe: Baseline and the mean of Days 28 and 29Population: 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.
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).
Outcome measures
| Measure |
PF-06291874 150 mg
n=33 Participants
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
|
Placebo
n=33 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=32 Participants
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
|
PF-06291874 75 mg
n=35 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Lipoprotein A
|
-15.15 % (percent change)
Standard Deviation 19.449
|
-4.38 % (percent change)
Standard Deviation 16.100
|
-12.78 % (percent change)
Standard Deviation 15.095
|
-13.48 % (percent change)
Standard Deviation 15.739
|
-13.17 % (percent change)
Standard Deviation 16.639
|
SECONDARY outcome
Timeframe: 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.
Maximum PF-06291874 plasma concentration.
Outcome measures
| Measure |
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
|
Placebo
n=35 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=31 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=35 Participants
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
|
PF-06291874 75 mg
n=33 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
—
|
714.3 ng/mL
Geometric Coefficient of Variation 25
|
1819 ng/mL
Geometric Coefficient of Variation 29
|
3560 ng/mL
Geometric Coefficient of Variation 28
|
8265 ng/mL
Geometric Coefficient of Variation 27
|
SECONDARY outcome
Timeframe: 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.
Time to maximum PF-06291874 plasma concentration.
Outcome measures
| Measure |
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
|
Placebo
n=35 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=31 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=35 Participants
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
|
PF-06291874 75 mg
n=33 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Time to Reach Cmax (Tmax)
|
—
|
6.00 hour (hr)
Interval 2.0 to 8.02
|
6.00 hour (hr)
Interval 2.0 to 8.02
|
6.00 hour (hr)
Interval 2.0 to 24.0
|
6.00 hour (hr)
Interval 3.92 to 8.02
|
SECONDARY outcome
Timeframe: 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.
Area under the PF-06291874 plasma concentration-time profile from time zero to time tau, the dosing interval, where tau=24 hours.
Outcome measures
| Measure |
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
|
Placebo
n=35 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=31 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=35 Participants
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
|
PF-06291874 75 mg
n=32 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
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
|
32370 ng*hr/mL
Geometric Coefficient of Variation 32
|
65230 ng*hr/mL
Geometric Coefficient of Variation 31
|
142900 ng*hr/mL
Geometric Coefficient of Variation 32
|
SECONDARY outcome
Timeframe: 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.
Minimum PF-06291874 plasma concentration.
Outcome measures
| Measure |
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
|
Placebo
n=35 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=31 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=35 Participants
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
|
PF-06291874 75 mg
n=32 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Minimum Plasma Concentration (Cmin)
|
—
|
350.6 ng/mL
Geometric Coefficient of Variation 46
|
666.4 ng/mL
Geometric Coefficient of Variation 305
|
1257 ng/mL
Geometric Coefficient of Variation 361
|
3247 ng/mL
Geometric Coefficient of Variation 233
|
SECONDARY outcome
Timeframe: 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.
Apparent oral clearance of PF-06291874.
Outcome measures
| Measure |
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
|
Placebo
n=35 Participants
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=31 Participants
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=35 Participants
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
|
PF-06291874 75 mg
n=32 Participants
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
|---|---|---|---|---|---|
|
Apparent Clearance (CL/F)
|
—
|
1.176 L/hr
Geometric Coefficient of Variation 29
|
1.082 L/hr
Geometric Coefficient of Variation 32
|
1.150 L/hr
Geometric Coefficient of Variation 31
|
1.050 L/hr
Geometric Coefficient of Variation 32
|
Adverse Events
Placebo
PF-06291874 15 mg
PF-06291874 35 mg
PF-06291874 75 mg
PF-06291874 150 mg
Serious adverse events
| Measure |
Placebo
n=34 participants at risk
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 participants at risk
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 participants at risk
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
|
PF-06291874 75 mg
n=35 participants at risk
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 150 mg
n=34 participants at risk
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
|
|---|---|---|---|---|---|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
2.9%
1/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
Other adverse events
| Measure |
Placebo
n=34 participants at risk
Participants received placebo (three 5/25 milligram \[mg\] and one 100 mg matching placebo tablets) once daily for 28 days
|
PF-06291874 15 mg
n=35 participants at risk
Participants received PF-06291874 15 mg (three 5 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 35 mg
n=34 participants at risk
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
|
PF-06291874 75 mg
n=35 participants at risk
Participants received PF-06291874 75 mg (three 25 mg tablets and one 100 mg placebo tablet) once daily for 28 days
|
PF-06291874 150 mg
n=34 participants at risk
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
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.9%
1/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
2.9%
1/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
8.8%
3/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
2.9%
1/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
8.8%
3/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
2.9%
1/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
8.8%
3/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
|
General disorders
Fatigue
|
0.00%
0/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
5.7%
2/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
|
Infections and infestations
Upper respiratory tract infection
|
5.9%
2/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
5.7%
2/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
8.8%
3/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
11.4%
4/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
2.9%
1/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
|
Nervous system disorders
Headache
|
2.9%
1/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
0.00%
0/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
8.8%
3/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
2.9%
1/35 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
2.9%
1/34 • From Baseline to 10-14 days after the last dose of the study drug, up to 42 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER