Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy, Safety And Tolerability Of PF-06743649 In Gout Subjects.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02187029
Recruitment Status : Terminated (B7911002 was prematurely discontinued due to a safety concern that led to decision to terminate the study on 10 Nov 2014)
First Posted : July 10, 2014
Results First Posted : November 11, 2016
Last Update Posted : November 11, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Gout
Interventions Drug: PF-06743649
Other: Placebo
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days. Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days. Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant. Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Period Title: Overall Study
Started 7 3 11 9
Completed 6 2 0 6
Not Completed 1 1 11 3
Reason Not Completed
Adverse Event             0             1             1             0
Study Terminated by Sponsor             0             0             10             3
Withdrawal by Subject             1             0             0             0
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo Total
Hide Arm/Group Description Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days. Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days. Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant. Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons. Total of all reporting groups
Overall Number of Baseline Participants 7 3 11 9 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 3 participants 11 participants 9 participants 30 participants
47.1  (8.1) 50.7  (9.7) 43.4  (9.8) 46.8  (9.3) 46.0  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 3 participants 11 participants 9 participants 30 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
7
 100.0%
3
 100.0%
11
 100.0%
9
 100.0%
30
 100.0%
1.Primary Outcome
Title Baseline of Serum Uric Acid
Hide Description An elevation in serum uric acid, hyperuricemia, is a prerequisite for the development of gout.
Time Frame Baseline (pre-dose Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Mean (Standard Deviation)
Unit of Measure: milligram per deciliter(mg/dL)
8.800  (1.1402) 9.100  (0.8185) 8.991  (0.6549) 9.278  (0.9536)
2.Primary Outcome
Title Percent Change From Baseline in Serum Uric Acid Level at 24 Hours Post Dose on Day 14
Hide Description [Not Specified]
Time Frame Day 14 Hour 24
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment. Number of participants analyzed is number of evaluable participants for this outcome measure. No data due to “Cohort 2: PF-06743649 5 mg” termination after 2 days of dosing.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 6 2 0 6
Mean (Standard Deviation)
Unit of Measure: percent (%)
-52.891  (6.1661) -67.480  (1.1498) -1.381  (9.1430)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Bayesian ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -52.550
Confidence Interval (2-Sided) 90%
-56.320 to -48.780
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Bayesian ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -66.310
Confidence Interval (2-Sided) 90%
-71.310 to -61.540
Estimation Comments [Not Specified]
3.Primary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state AEs included both serious and non-serious events.
Time Frame Baseline up to 28 days after last study drug administration (Day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study medication.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Measure Type: Number
Unit of Measure: participants
Participants with AEs 2 3 3 4
Participants with SAEs 0 0 1 0
4.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities
Hide Description Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters include hematology (Hemoglobin, Hematocrit, red blood cell [RBC] count, Platelet count, mean corpuscular volume [MCV], mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration [MCHC], white blood cell [WBC] count, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes), hematocrit (blood urea nitrogen [BUN]/urea and Creatinine, Glucose , Calcium, Sodium, Potassium, Chloride, Total CO2 [Bicarbonate], aspartate transaminase [AST], alanine transaminase [ALT], Total Bilirubin, Alkaline phosphatase, Albumin, Total protein, Thyroid Stimulating Hormone [TSH], free T3 [FT3] and free T4 [FT4] ), urinalysis (pH, Glucose [qual], Protein, Blood, Ketones, Nitrites, Leukocyte esterase, Urobilinogen, Urine bilirubin, Microscopy [including crystals]) and other (follicle-stimulating hormone [FSH], Urine drug screen).
Time Frame Baseline up to follow up visit (Day 25-29)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study medication.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Measure Type: Number
Unit of Measure: participants
1 1 3 2
5.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Vital Signs Findings
Hide Description Criteria for potential clinically important change in vital signs included: Systolic blood pressure (BP) less than (<) 90 millimeters of mercury (mmHg) or more than or equal to (>=)30 mmHg change from baseline, diastolic BP of <50 mmHg or >=20 mmHg change from baseline, Supine pulse rate of <40 or more than (>)120 beats per minute (bpm).
Time Frame Baseline up to follow up visit (Day 25-29)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study medication.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Measure Type: Number
Unit of Measure: participants
Supine Systolic BP (mmHg) <90 0 0 0 0
Supine Diastolic BP (mmHg) <50 0 0 0 0
Supine Pulse Rate (bpm) <40 0 0 0 0
Supine Pulse Rate (bpm) >120 0 0 0 0
Increase Supine Systolic BP (mmHg) >=30 1 0 1 1
Increase Supine Diastolic BP (mmHg) >=20 1 0 1 1
Decrease Supine Systolic BP (mmHg) >=30 0 0 1 0
Decrease Supine Diastolic BP (mmHg) >=20 0 0 1 0
6.Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria
Hide Description Criteria for potential clinically important changes in ECG (12-lead) were defined as: 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) or increase from baseline >=25% when baseline >200 msec or increase from baseline >=50% when baseline less than or equal to (<=) 200 msec; time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS) interval >=140 msec or >=50% increase from baseline; the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval corrected using the Fridericia formula (QTcF) of 450 to < 480 msec, 480 to <500 msec and >=500 msec, or an increase of 30 to <60 msec or >=60 msec from baseline.
Time Frame Baseline up to Day 16
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study medication.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Measure Type: Number
Unit of Measure: participants
PR (msec) >=300 0 0 0 0
QRS complex (msec) >=140 0 0 0 0
QTCF (msec) 450-<480 0 0 0 0
QTCF (msec) 480-<500 0 0 0 0
QTCF (msec) >=500 0 0 0 0
PR increase from baseline >=25/50% 0 0 0 0
QRS complex increase from baseline >=50% 0 0 0 0
QTCF increase from baseline 30 to <60 msec 0 0 0 0
QTCF increase from baseline >=60 msec 0 0 0 0
7.Secondary Outcome
Title Change From Baseline in Serum Uric Acid Levels at Day 1, Day 3, Day 7, Day 11, Day 14 and Follow-up
Hide Description [Not Specified]
Time Frame Day 1, Day 3, Day 7, Day 11, Day 14 and follow-up visit (Day 25-29)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline (n=7,3,11,9) 8.80  (1.140) 9.10  (0.819) 8.99  (0.655) 9.28  (0.954)
Day 1, Hour 1 (n=6,3,11, 9) -0.18  (0.194) -0.50  (0.436) -0.51  (0.353) 0.11  (0.190)
Day 1, Hour 2 (n=7,3,11,9) -0.69  (0.261) -1.17  (0.839) -1.27  (0.403) -0.02  (0.156)
Day 1, Hour 4 (n=7,3,11,9) -1.47  (0.293) -3.07  (0.115) -2.30  (0.382) -0.12  (0.233)
Day 1, Hour 8 (n=7,3,11,9) -2.00  (0.716) -3.87  (0.473) -2.77  (0.623) -0.23  (0.320)
Day 1, Hour 12 (n=7,3,11,9) -1.77  (0.704) -3.83  (0.577) -2.74  (0.721) -0.19  (0.389)
Day 1, Hour 24 (n=7,3,11,9) -1.69  (0.664) -3.43  (0.757) -2.04  (0.770) -0.18  (0.396)
Day 3 (n=7,3,10,9) -2.13  (0.921) -4.50  (0.529) -3.02  (0.925) 0.08  (0.342)
Day 7, pre-dose (n=7,2,0,6) -2.60  (0.945) -5.75  (0.212) NA [1]   (NA) -0.07  (0.734)
Day 7, Hour 1 (n=7,2,0,6) -2.64  (0.846) -5.75  (0.212) NA [1]   (NA) -0.03  (0.787)
Day 7, Hour 2 (n=7,2,0,6) -2.94  (0.838) -6.10  (0.283) NA [1]   (NA) -0.05  (0.797)
Day 7, Hour 4 (n=7,2,0,6) -3.44  (0.873) -6.60  (0.283) NA [1]   (NA) -0.22  (0.731)
Day 7, Hour 8 (n=7,2,0,6) -3.49  (0.996) -6.60  (0.141) NA [1]   (NA) -0.38  (0.578)
Day 7, Hour 12 (n=7,2,0,6) -3.24  (1.037) -6.45  (0.071) NA [1]   (NA) -0.25  (0.599)
Day 7, Hour 24 (n=7,2,0,6) -2.73  (0.955) -5.90  (0.141) NA [1]   (NA) -0.17  (0.794)
Day 11 (n=6,2,0,6) -4.80  (0.961) -5.75  (0.071) NA [1]   (NA) -0.17  (0.845)
Day 14, pre-dose (n=6,2,0,6) -4.57  (0.900) -5.75  (0.636) NA [1]   (NA) -0.22  (0.747)
Day 14, Hour 1 (n=6,2,0,6) -4.83  (0.799) -6.05  (0.495) NA [1]   (NA) -0.23  (0.659)
Day 14, Hour 2 (n=6,2,0,6) -5.35  (0.846) -6.35  (0.495) NA [1]   (NA) -0.33  (0.680)
Day 14, Hour 4 (n=6,2,0,6) -6.02  (0.906) -6.80  (0.566) NA [1]   (NA) -0.55  (0.638)
Day 14, Hour 8 (n=6,2,0,6) -5.93  (1.001) -6.85  (0.636) NA [1]   (NA) -0.33  (0.781)
Day 14, Hour 12 (n=6,2,0,6) -5.67  (1.124) -6.60  (0.566) NA [1]   (NA) -0.28  (0.725)
Day 14, Hour 24 (n=6,2,0,6) -4.85  (0.940) -5.90  (0.424) NA [1]   (NA) -0.20  (0.834)
Follow-up (Day 25-29) (n=6,3,10,9) -0.93  (1.422) -2.27  (2.593) 0.45  (0.938) -0.30  (1.648)
[1]
No data due to cohort termination after 2 days of dosing.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.30
Confidence Interval 90%
-0.55 to -0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.62
Confidence Interval (2-Sided) 90%
-0.95 to -0.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.19
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.34
Confidence Interval (2-Sided) 90%
-1.52 to -1.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.86
Confidence Interval (2-Sided) 90%
-2.38 to -1.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.83
Confidence Interval (2-Sided) 90%
-2.18 to -1.48
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.19
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.74
Confidence Interval (2-Sided) 90%
-2.11 to -1.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.48
Confidence Interval (2-Sided) 90%
-2.89 to -2.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.75
Confidence Interval (2-Sided) 90%
-3.29 to -2.20
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.80
Confidence Interval (2-Sided) 90%
-3.39 to -2.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.06
Confidence Interval (2-Sided) 90%
-3.72 to -2.41
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day7, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.40
Confidence Interval (2-Sided) 90%
-4.03 to -2.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.30
Confidence Interval (2-Sided) 90%
-3.82 to -2.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.20
Confidence Interval (2-Sided) 90%
-3.72 to -2.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.81
Confidence Interval (2-Sided) 90%
-3.30 to -2.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.56
Confidence Interval (2-Sided) 90%
-5.19 to -3.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.32
Confidence Interval (2-Sided) 90%
-4.75 to -3.88
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.55
Confidence Interval (2-Sided) 90%
-5.02 to -4.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.97
Confidence Interval (2-Sided) 90%
-5.47 to -4.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.43
Confidence Interval (2-Sided) 90%
-5.83 to -5.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.22
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.57
Confidence Interval (2-Sided) 90%
-6.08 to -5.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.34
Confidence Interval (2-Sided) 90%
-5.86 to -4.82
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.65
Confidence Interval (2-Sided) 90%
-5.12 to -4.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Follow-up, Day 25-29
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.09
Confidence Interval (2-Sided) 90%
-2.97 to 0.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.03
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.62
Confidence Interval (2-Sided) 90%
-0.92 to -0.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.18
Confidence Interval (2-Sided) 90%
-1.61 to -0.75
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.24
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.91
Confidence Interval (2-Sided) 90%
-3.14 to -2.69
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.70
Confidence Interval (2-Sided) 90%
-4.36 to -3.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.84
Confidence Interval (2-Sided) 90%
-4.28 to -3.40
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.24
Estimation Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.47
Confidence Interval 90%
-3.94 to -3.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.76
Confidence Interval (2-Sided) 90%
-5.29 to -4.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.81
Confidence Interval (2-Sided) 90%
-6.62 to -5.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.84
Confidence Interval (2-Sided) 90%
-6.72 to -4.95
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.49
Estimation Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.18
Confidence Interval (2-Sided) 90%
-7.17 to -5.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.55
Estimation Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.51
Confidence Interval (2-Sided) 90%
-7.46 to -5.55
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.29
Confidence Interval (2-Sided) 90%
-7.07 to -5.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.24
Confidence Interval (2-Sided) 90%
-7.03 to -5.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 37 Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.75
Confidence Interval (2-Sided) 90%
-6.50 to -4.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 38 Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg
Comments Day 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.62
Confidence Interval (2-Sided) 90%
-6.59 to -4.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 39 Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.76
Confidence Interval (2-Sided) 90%
-6.42 to -5.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 40 Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.96
Confidence Interval (2-Sided) 90%
-6.67 to -5.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 41 Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.14
Confidence Interval (2-Sided) 90%
-6.90 to -5.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 42 Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.42
Confidence Interval (2-Sided) 90%
-7.03 to -5.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 43 Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.64
Confidence Interval (2-Sided) 90%
-7.41 to -5.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 44 Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.40
Confidence Interval (2-Sided) 90%
-7.18 to -5.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 45 Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.77
Confidence Interval (2-Sided) 90%
-6.47 to -5.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.38
Estimation Comments [Not Specified]
Show Statistical Analysis 46 Hide Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Follow-up, Day 25-29
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.66
Confidence Interval (2-Sided) 90%
-4.96 to -0.35
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.26
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants Reaching Serum Uric Acid Levels <6, <5 and <4 mg/dL at 24 Hours Post Dose on Day 7 and Day 14
Hide Description Number of participants reaching serum uric acid levels <6, <5 and <4 mg/dL at 7 and 14 days after initiation.
Time Frame 24 hours post dose on Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 0 9
Measure Type: Number
Unit of Measure: participants
Day 7 (<6.0) 4 2 0
Day 7 (<5.0) 0 2 0
Day 7 (<4.0) 0 2 0
Day 14 (<6.0) 6 2 0
Day 14 (<5.0) 6 2 0
Day 14 (<4.0) 1 2 0
9.Secondary Outcome
Title Incidence and Severity of Gout Flare Attacks
Hide Description [Not Specified]
Time Frame Baseline up to Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Measure Type: Number
Unit of Measure: participants
0 0 0 0
10.Secondary Outcome
Title Duration of Gout Flare Attacks
Hide Description Duration of gout flare attacks with participants who developed gout flare attacks.
Time Frame Baseline up to Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who developed gout flare attacks (Duration was not assessed as no participant developed gout flare attacks).
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Plasma Levels of PF-06743649 After Initiation of Dosing at Day 1, Day 7, and Day 14
Hide Description Data has been calculated by setting concentration values below the lower limit of quantification to zero. The lower limit of quantification was 10.0 nanograms per milliliter (ng/mL).
Time Frame 0, 1, 2, 4, 8, 12 and 24 hours at Day 1, Day 7, and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized and treated who have at least 1 measureable concentration; n=number of participants analyzed in each respective arm.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Overall Number of Participants Analyzed 7 3 11
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1, Hour 0 (n=7,3,11) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Day 1, Hour 1 (n=7,3,11) 163.8  (84.336) 1097  (1011.8) 371.3  (239.52)
Day 1, Hour 2 (n=7,3,11) 196.6  (47.367) 1570  (416.77) 454.7  (141.62)
Day 1, Hour 4 (n=7,3,11) 105.8  (34.342) 1081  (189.22) 282.4  (106.48)
Day 1, Hour 8 (n=7,3,11) 47.27  (19.596) 523.3  (108.89) 142.7  (87.111)
Day 1, Hour 12 (n=7,3,11) 26.84  (13.738) 229.3  (36.665) 99.27  (70.301)
Day 1, Hour 24 (n=7,3,11) 7.586  (10.183) 86.67  (18.434) 48.90  (49.583)
Day 7, Hour 0 (n=7,2,0) 10.50  (10.560) 154.0  (41.012) NA [2]   (NA)
Day 7, Hour 1 (n=7,2,0) 185.9  (102.26) 1275  (261.63) NA [2]   (NA)
Day 7, Hour 2 (n=7,2,0) 211.7  (95.552) 2715  (487.90) NA [2]   (NA)
Day 7, Hour 4 (n=7,2,0) 137.3  (43.222) 1520  (183.85) NA [2]   (NA)
Day 7, Hour 8 (n=7,2,0) 67.59  (19.509) 697.0  (49.497) NA [2]   (NA)
Day 7, Hour 12 (n=7,2,0) 42.30  (16.272) 457.5  (78.489) NA [2]   (NA)
Day 7, Hour 24 (n=7,2,0) 12.50  (10.356) 147.0  (31.113) NA [2]   (NA)
Day 14, Hour 0 (n=6,2,0) 47.08  (27.363) 157.5  (43.134) NA [2]   (NA)
Day 14, Hour 1 (n=6,2,0) 736.7  (483.18) 1995  (417.19) NA [2]   (NA)
Day 14, Hour 2 (n=6,2,0) 729.5  (218.79) 2140  (325.27) NA [2]   (NA)
Day 14, Hour 4 (n=6,2,0) 429.5  (165.51) 1480  (325.27) NA [2]   (NA)
Day 14, Hour 8 (n=6,2,0) 245.8  (99.385) 687.0  (96.167) NA [2]   (NA)
Day 14, Hour 12 (n=6,2,0) 163.3  (73.480) 400.0  (74.953) NA [2]   (NA)
Day 14, Hour 24 (n=6,2,0) 54.27  (34.849) 133.5  (13.435) NA [2]   (NA)
[1]
Data was not reported because the observations were not above lower limit of quantification.
[2]
No data due to cohort termination after 2 days of dosing.
12.Secondary Outcome
Title Plasma Levels of PF-06743648 After Initiation of Dosing at Day 1, Day 7, and Day 14
Hide Description PF-06743648 is an active metabolite of PF-06743649. Data has been calculated by setting concentration values below the lower limit of quantification to zero. The lower limit of quantification was 2.00 nanograms per milliliter (ng/mL).
Time Frame Day 1, Day 7, and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Overall Number of Participants Analyzed 7 3 11
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1, Hour 0 (n=7,3,11) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Day 1, Hour 1 (n=7,3,11) 6.713  (6.6738) 79.62  (82.093) 13.81  (10.519)
Day 1, Hour 2 (n=7,3,11) 28.69  (14.265) 245.6  (182.75) 49.30  (26.599)
Day 1, Hour 4 (n=7,3,11) 30.07  (7.3081) 395.0  (69.936) 59.21  (29.231)
Day 1, Hour 8 (n=7,3,11) 18.09  (5.4462) 261.3  (53.003) 38.25  (18.527)
Day 1, Hour 12 (n=7,3,11) 11.46  (3.4996) 156.3  (22.591) 25.67  (13.251)
Day 1, Hour 24 (n=7,3,11) 6.059  (2.8621) 76.27  (23.811) 12.76  (7.3997)
Day 7, Hour 0 (n=7,2,0) 7.259  (3.5055) 70.50  (11.597) NA [2]   (NA)
Day 7, Hour 1 (n=7,2,0) 22.00  (9.8895) 107.0  (1.4142) NA [2]   (NA)
Day 7, Hour 2 (n=7,2,0) 42.83  (20.763) 344.0  (49.497) NA [2]   (NA)
Day 7, Hour 4 (n=7,2,0) 40.26  (13.353) 397.0  (9.8995) NA [2]   (NA)
Day 7, Hour 8 (n=7,2,0) 26.64  (9.2428) 261.0  (0.00000) NA [2]   (NA)
Day 7, Hour 12 (n=7,2,0) 16.67  (5.5011) 167.5  (23.335) NA [2]   (NA)
Day 7, Hour 24 (n=7,2,0) 8.470  (3.7998) 91.80  (1.9799) NA [2]   (NA)
Day 14, Hour 0 (n=6,2,0) 21.99  (9.6890) 76.60  (9.4752) NA [2]   (NA)
Day 14, Hour 1 (n=6,2,0) 74.72  (37.910) 171.0  (26.870) NA [2]   (NA)
Day 14, Hour 2 (n=6,2,0) 139.3  (53.432) 390.0  (117.38) NA [2]   (NA)
Day 14, Hour 4 (n=6,2,0) 127.3  (37.255) 364.0  (18.385) NA [2]   (NA)
Day 14, Hour 8 (n=6,2,0) 74.82  (39.810) 280.5  (9.1924) NA [2]   (NA)
Day 14, Hour 12 (n=6,2,0) 49.07  (27.960) 162.0  (1.4142) NA [2]   (NA)
Day 14, Hour 24 (n=6,2,0) 27.32  (14.608) 81.35  (1.2021) NA [2]   (NA)
[1]
Data was not reported because the observations were not above lower limit of quantification.
[2]
No data due to cohort termination after 2 days of dosing.
13.Secondary Outcome
Title Change From Baseline in Plasma Levels of Xanthine at Day 1, Day 7, Day 14, and at Follow-up
Hide Description Change in plasma levels of xanthine from baseline at time points 0 (prior to dosing except on Day 1), 1, 2, 4, 8, 12 and 24 hours following dosing with PF-06743649 or placebo on days 1, 7 and 14 as well prior to dosing on days 3 and 11 and at follow-up of treatment with PF-06743649 or placebo.
Time Frame Baseline, Day 1, Day 7, Day 14, and at follow-up visit (Day 25-29)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/mL)
Baseline (n=7,3,11,9) 0.2519  (0.04316) 0.2680  (0.10095) 0.2102  (0.04037) 0.2257  (0.05304)
Day 1, Hour 1 (n=7,3,11,9) -0.0473  (0.05949) 0.1057  (0.02155) -0.0192  (0.04214) -0.0112  (0.08230)
Day 1, Hour 2 (n=7,3,11,9) -0.0330  (0.03844) 0.3667  (0.27216) 0.0346  (0.05090) -0.0220  (0.03653)
Day 1, Hour 4 (n=7,3,11,9) -0.0826  (0.04922) 0.3317  (0.11558) -0.0306  (0.05783) -0.0511  (0.06510)
Day 1, Hour 8 (n=7,3,11,9) -0.0859  (0.07603) 0.1947  (0.14431) -0.0918  (0.02295) -0.0982  (0.3674)
Day 1, Hour 12 (n=7,3,11,9) -0.1117  (0.04270) 0.0847  (0.11634) -0.0921  (0.03801) -0.0786  (0.05731)
Day 1, Hour 24 (n=7,3,11,9) 0.0167  (0.08149) 0.1927  (0.04879) 0.0140  (0.03411) 0.0233  (0.10687)
Day 7, pre-dose (n=7,2,0,6) -0.0362  (0.07118) 0.1450  (0.00283) NA [1]   (NA) 0.0177  (0.13598)
Day 7, Hour 1 (n=7,2,0,6) -0.0061  (0.10488) 0.1765  (0.07566) NA [1]   (NA) -0.0170  (0.07475)
Day 7, Hour 2 (n=7,2,0,6) 0.0231  (0.05070) 0.5300  (0.21779) NA [1]   (NA) -0.0098  (0.08066)
Day 7, Hour 4 (n=7,2,0,6) -0.0147  (0.06839) 0.4995  (0.14920) NA [1]   (NA) -0.0233  (0.07942)
Day 7, Hour 8 (n=7,2,0,6) -0.1086  (0.04749) 0.3010  (0.14425) NA [1]   (NA) -0.0843  (0.05064)
Day 7, Hour 12 (n=7,2,0,6) -0.1276  (0.04658) -0.0535  (0.01909) NA [1]   (NA) -0.0750  (0.04685)
Day 7, Hour 24 (n=7,2,0,6) -0.0540  (0.05434) 0.1465  (0.07990) NA [1]   (NA) -0.0242  (0.06072)
Day 14, pre-dose (n=6,2,0,6) -0.0290  (0.05418) 0.1540  (0.07778) NA [1]   (NA) -0.0120  (0.02367)
Day 14, Hour 1 (n=6,2,0,6) 0.0607  (0.06662) 0.3515  (0.10819) NA [1]   (NA) -0.0008  (0.02699)
Day 14, Hour 2 (n=6,2,0,6) 0.1353  (0.09010) 0.5960  (0.01131) NA [1]   (NA) 0.0330  (0.09579)
Day 14, Hour 4 (n=6,2,0,6) -0.0148  (0.09997) 0.5595  (0.00212) NA [1]   (NA) -0.0210  (0.07869)
Day 14, Hour 8 (n=6,2,0,6) -0.0655  (0.08041) 0.2030  (0.11738) NA [1]   (NA) -0.0778  (0.06107)
Day 14, Hour 12 (n=6,2,0,6) -0.0986  (0.04973) 0.1175  (0.18031) NA [1]   (NA) -0.0801  (0.04477)
Day 14, Hour 24 (n=6,2,0,6) -0.0172  (0.08536) 0.1695  (0.08132) NA [1]   (NA) 0.0242  (0.06158)
Follow-up (Day 25-29) (n=6,3,10,9) 0.3710  (0.92324) 0.8263  (0.77448) 0.1161  (0.18229) 0.2299  (0.44888)
[1]
No data due to cohort termination after 2 days of dosing.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0355
Confidence Interval (2-Sided) 90%
-0.1103 to 0.0394
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0423
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0152
Confidence Interval (2-Sided) 90%
-0.1269 to 0.0966
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0631
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0331
Confidence Interval (2-Sided) 90%
-0.1078 to 0.0417
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0422
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0035
Confidence Interval (2-Sided) 90%
-0.0750 to 0.0820
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0443
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0502
Confidence Interval (2-Sided) 90%
-0.1153 to 0.0149
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0367
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0080
Confidence Interval (2-Sided) 90%
-0.1058 to 0.0899
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0553
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0539
Confidence Interval (2-Sided) 90%
-0.1538 to 0.0460
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0561
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0109
Confidence Interval (2-Sided) 90%
-0.0793 to 0.1010
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0506
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0330
Confidence Interval (2-Sided) 90%
-0.0554 to 0.1213
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0496
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0086
Confidence Interval (2-Sided) 90%
-0.0733 to 0.0905
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0459
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0244
Confidence Interval (2-Sided) 90%
-0.0865 to 0.0378
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0349
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0526
Confidence Interval (2-Sided) 90%
-0.0973 to -0.0079
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0251
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0298
Confidence Interval (2-Sided) 90%
-0.0889 to 0.0292
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0331
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0167
Confidence Interval (2-Sided) 90%
-0.0649 to 0.0315
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0268
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0616
Confidence Interval (2-Sided) 90%
0.0010 to 0.1222
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0337
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1025
Confidence Interval (2-Sided) 90%
0.0104 to 0.1945
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0512
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0062
Confidence Interval (2-Sided) 90%
-0.0827 to 0.0952
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0495
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0124
Confidence Interval (2-Sided) 90%
-0.0672 to 0.0919
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0443
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0186
Confidence Interval (2-Sided) 90%
-0.0918 to 0.0547
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0408
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0413
Confidence Interval (2-Sided) 90%
-0.1192 to 0.0365
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0433
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Follow-up, Day 25-29
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.4011
Confidence Interval (2-Sided) 90%
-0.2968 to 1.0990
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3916
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1175
Confidence Interval (2-Sided) 90%
0.0223 to 0.2127
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0537
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3845
Confidence Interval (2-Sided) 90%
0.2424 to 0.5266
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0802
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3812
Confidence Interval (2-Sided) 90%
0.2862 to 0.4762
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0536
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.2841
Confidence Interval (2-Sided) 90%
0.1843 to 0.3838
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0563
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1462
Confidence Interval (2-Sided) 90%
0.0635 to 0.2289
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0467
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1680
Confidence Interval (2-Sided) 90%
0.0436 to 0.2924
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0702
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1303
Confidence Interval (2-Sided) 90%
-0.0172 to 0.2778
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0830
Estimation Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1953
Confidence Interval 90%
0.0625 to 0.3281
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0747
Estimation Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.5409
Confidence Interval (2-Sided) 90%
0.4110 to 0.6707
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0729
Estimation Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.5235
Confidence Interval (2-Sided) 90%
0.4032 to 0.6438
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0675
Estimation Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3857
Confidence Interval (2-Sided) 90%
0.2944 to 0.4769
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0512
Estimation Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0216
Confidence Interval (2-Sided) 90%
-0.0439 to 0.0872
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0368
Estimation Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1708
Confidence Interval (2-Sided) 90%
0.0841 to 0.2574
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0486
Estimation Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1660
Confidence Interval (2-Sided) 90%
0.0982 to 0.2338
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0377
Estimation Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3524
Confidence Interval (2-Sided) 90%
0.2667 to 0.4380
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0477
Estimation Comments [Not Specified]
Show Statistical Analysis 37 Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.5631
Confidence Interval (2-Sided) 90%
0.4330 to 0.6932
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0724
Estimation Comments [Not Specified]
Show Statistical Analysis 38 Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.5807
Confidence Interval (2-Sided) 90%
0.4549 to 0.7065
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0700
Estimation Comments [Not Specified]
Show Statistical Analysis 39 Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.2814
Confidence Interval (2-Sided) 90%
0.1688 to 0.3940
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0627
Estimation Comments [Not Specified]
Show Statistical Analysis 40 Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1982
Confidence Interval (2-Sided) 90%
0.0945 to 0.3019
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0577
Estimation Comments [Not Specified]
Show Statistical Analysis 41 Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Day 14, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1465
Confidence Interval (2-Sided) 90%
0.0361 to 0.2569
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0615
Estimation Comments [Not Specified]
Show Statistical Analysis 42 Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 40 mg, Cohort 1 and 2: Placebo
Comments Follow-up, Day 25-29
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.8565
Confidence Interval (2-Sided) 90%
0.0017 to 1.7112
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4796
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Plasma Levels of Hypoxanthine at Day 1, Day 7, Day 14, and at Follow-up
Hide Description [Not Specified]
Time Frame Day 1, Day 7, Day 14, and at follow-up visit (Day 25-29)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and who received at least 1 dose of randomization treatment; n=number of participants analyzed in each respective arm.
Arm/Group Title Cohort 1: PF-06743649 2.5 mg to 10 mg Cohort 1: PF-06743649 40 mg Cohort 2: PF-06743649 5 mg Cohort 1 and 2: Placebo
Hide Arm/Group Description:
Following a dose titration regimen, participants received PF-06743649 2.5 mg tablet orally once daily (QD) for 8 days, followed by PF-06743649 10 mg QD for 6 days.
Prior to dose titration, participants received PF-06743649 40 mg tablet orally QD for 14 days.
Participants received PF-06743649 5 mg tablets QD for 2 days before the study was terminated for safety reasons. This cohort was stopped after acute kidney injury was reported in 1 participant.
Participants received placebo matched tablet orally once daily . Participants in Cohort 1 received placebo for 14 days and participants in Cohort 2 received placebo for 2 days before the study was terminated for safety reasons.
Overall Number of Participants Analyzed 7 3 11 9
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Baseline (n=7,3,11,9) 0.9604  (0.15380) 1.0060  (0.41079) 0.8677  (0.18896) 0.8922  (0.13486)
Day 1, Hour 1 (n=7,3,11,9) -0.2539  (0.24173) 0.1440  (0.56564) -0.1205  (0.16427) 0.0847  (0.41097)
Day 1, Hour 2 (n=7,3,11,9) -0.2229  (0.08132) 0.2130  (0.40812) -0.0145  (0.13714) -0.0421  (0.21113)
Day 1, Hour 4 (n=7,3,11,9) -0.2774  (0.19696) 0.0717  (0.62608) -0.1426  (0.14932) -0.0369  (0.32185)
Day 1, Hour 8 (n=7,3,11,9) -0.2000  (0.27433) 0.1760  (0.78402) -0.1895  (0.18641) -0.1870  (0.26137)
Day 1, Hour 12 (n=7,3,11,9) -0.2973  (0.13666) 0.2703  (0.62935) -0.0979  (0.15883) -0.0967  (0.22579)
Day 1, Hour 24 (n=7,3,11,9) -0.0937  (0.30529) 0.5607  (0.66507) -0.0039  (0.10751) 0.1200  (0.48900)
Day 7, pre-dose (n=7,2,0,6) -0.1309  (0.31653) 0.0810  (0.21355) NA [1]   (NA) 0.1317  (0.57974)
Day 7, Hour 1 (n=7,2,0,6) -0.1089  (0.40558) -0.1575  (0.46598) NA [1]   (NA) -0.0285  (0.43096)
Day 7, Hour 2 (n=7,2,0,6) -0.0923  (0.11659) 0.1360  (0.67317) NA [1]   (NA) -0.0103  (0.35162)
Day 7, Hour 4 (n=7,2,0,6) -0.0067  (0.28262) -0.2505  (0.37406) NA [1]   (NA) 0.0762  (0.37371)
Day 7, Hour 8 (n=7,2,0,6) -0.2610  (0.30443) -0.0495  (0.61023) NA [1]   (NA) -0.0543  (0.35172)
Day 7, Hour 12 (n=7,2,0,6) -0.2860  (0.21522) -0.5290  (0.32951) NA [1]   (NA) -0.1557  (0.15279)
Day 7, Hour 24 (n=7,2,0,6) -0.1926  (0.18082) 0.1410  (0.68024) NA [1]   (NA) -0.0680  (0.35421)
Day 14, pre-dose (n=6,2,0,6) -0.2573  (0.23823) 0.0710  (0.24183) NA [1]   (NA) -0.0978  (0.10319)
Day 14, Hour 1 (n=6,2,0,6) -0.2292  (0.13816) 0.1660  (0.30547) NA [1]   (NA) -0.1065  (0.19276)
Day 14, Hour 2 (n=6,2,0,6) -0.1970  (0.20110) 0.2860  (0.29133) NA [1]   (NA) 0.0047  (0.25228)
Day 14, Hour 4 (n=6,2,0,6) -0.3627  (0.22065) 0.1210  (0.42568) NA [1]   (NA) 0.0133  (0.30407)
Day 14, Hour 8 (n=6,2,0,6) -0.2898  (0.32120) -0.2310  (0.16829) NA [1]   (NA) -0.0698  (0.34513)
Day 14, Hour 12 (n=6,2,0,6) -0.2415  (0.19015) 0.0510  (0.11455) NA [1]   (NA) -0.1075  (0.20019)
Day 14, Hour 24 (n=6,2,0,6) -0.2030  (0.23638) 0.2260  (0.36204) NA [1]   (NA) 0.0855  (0.36310)
Follow-up Day 25-29 (n=6,3,10,9) -0.0965  (0.43007) -0.2550  (0.91149) 0.3204  (0.30373) 0.3778  (0.73741)
[1]
No data due to cohort termination after 2 days of dosing.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.348
Confidence Interval (2-Sided) 90%
-0.707 to 0.010
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.209
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.179
Confidence Interval (2-Sided) 90%
-0.533 to 0.175
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.205
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.258
Confidence Interval (2-Sided) 90%
-0.568 to 0.052
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.180
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.046
Confidence Interval 90%
-0.390 to 0.298
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.201
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.284
Confidence Interval 90%
-0.575 to 0.006
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.168
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 1, Hour 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.166
Confidence Interval (2-Sided) 90%
-0.569 to 0.237
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.235
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, pre-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.263
Confidence Interval (2-Sided) 90%
-0.657 to 0.132
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.230
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-06743649 2.5 mg to 10 mg, Cohort 1 and 2: Placebo
Comments Day 7, Hour 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.080
Confidence Interval (2-Sided) 90%
-0.460 to 0.299