Clinical trial NCT04037865
Conditions: Renal Impairment
Sponsor: Pfizer
Start date: 2019-08-19; Completion date: 2020-03-31
Enrollment: 8 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 1 non-randomized, open-label, parallel cohort study of PF-06651600 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with mild and moderate renal impairment (Part 2).

Detailed description:
This is a Phase 1 non-randomized, open-label, parallel cohort, multi-site study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-06651600 after multiple oral doses of 50 mg daily. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately 16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted with approximately 8 subjects each with moderate and mild renal impairment. The total duration of participation from Screening visit to Day 11 will be a maximum of 39 days and from Screening visit to Follow-up/Contact Visit will a maximum of 73 days.

Arms: arm 1: This arm includes participants with severe renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10 arm 2: This arm includes participants with normal renal function who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10 arm 3: This arm is in Part 2 which will be conducted if decision criterion to proceed to Part 2 is met. This arm includes participants with moderate renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10 arm 4: This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10.
Interventions: intervention 1: PF-06651600
Intervention descriptions: intervention 1: PF-06651600 50 mg oral tablets will be administered on Days 1 to 10

Protocol documents:
Prot_000.pdf: 













































































































































































SAP_001.pdf: 
Protocol B7981020 (PF-06651600) Statistical Analysis Plan
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PFIZER CONFIDENTIAL
Protocol B7981020
A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO 
EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF 
PF-06651600 IN PARTICIPANTS WITH RENAL IMPAIRMENT AND IN HEALTHY 
PARTICIPANTS WITH NORMAL RENAL FUNCTION
Statistical Analysis Plan 
(SAP)
Version:
1.0
Author: 
Date: 01-JUL-2019
PPD


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PFIZER CONFIDENTIAL
Revision History
Version
Date
Author(s)
Summary of Changes/Comments
1.0
Ju1y 01, 2019
Not Applicable
NOTE: Italicized text within this document has been taken verbatim from the Protocol.
PPD


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PFIZER CONFIDENTIAL
TABLE OF CONTENTS 
LIST OF TABLES.....................................................................................................................4
LIST OF FIGURES ...................................................................................................................4
APPENDICES ...........................................................................................................................4
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Design .............................................................................................................5
2.2. Study Objectives .......................................................................................................9
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................9
4. HYPOTHESES AND DECISION RULES...........................................................................9
4.1. Statistical Hypotheses ...............................................................................................9
4.2. Statistical Decision Rules..........................................................................................9
5. ANALYSIS SETS ...............................................................................................................10
5.1. Pharmacokinetic (PK) Analysis Set ........................................................................10
5.1.1. Concentration Analysis Set.........................................................................10
5.1.2. Parameter Analysis Set...............................................................................10
5.2. Pharmacodynamic Analysis Set..............................................................................10
5.3. Safety Analysis Set..................................................................................................10
5.4. Other Analysis Sets .................................................................................................10
5.5. Treatment/Group Misallocations.............................................................................10
5.6. Protocol Deviations.................................................................................................10
5.6.1. Deviations Assessed Prior to Randomization.............................................10
5.6.2. Deviations Assessed Post-Randomization..................................................11
6. ENDPOINTS AND COVARIATES ...................................................................................11
6.1. Efficacy Endpoint(s) ...............................................................................................11
6.2. Safety Endpoints .....................................................................................................11
6.3. Other Endpoints.......................................................................................................11
6.3.1. PK Endpoints..............................................................................................11
6.3.2. PD Endpoints..............................................................................................12
6.4. Covariates................................................................................................................12
7. HANDLING OF MISSING VALUES ................................................................................12
7.1. Concentrations Below the Limit of Quantification.................................................12
7.2. Deviations, Missing Concentrations and Anomalous Values .................................12


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PFIZER CONFIDENTIAL
7.3. Pharmacokinetic Parameters ...................................................................................12
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................13
8.1. Statistical Methods ..................................................................................................13
8.2. Statistical Analyses .................................................................................................13
8.3. Safety Analysis........................................................................................................15
8.3.1. Treatment and Disposition of Subjects.......................................................15
8.3.2. Demographic and Clinical Examination Data............................................15
8.3.3. Discontinuation(s).......................................................................................16
8.3.4. Adverse Events...........................................................................................16
8.3.5. Laboratory Data..........................................................................................16
8.3.6. Vital Signs Data..........................................................................................16
8.3.7. ECG Data....................................................................................................16
8.3.8. Other Safety Data .......................................................................................16
8.3.9. Concomitant Treatments.............................................................................16
8.3.10. eGFR (estimated Glomerular Filtration Rate) Data..................................16
8.3.11. Screening and Other Special Purpose Data ..............................................16
9. REFERENCES ....................................................................................................................17
10. APPENDICES ...................................................................................................................18
LIST OF TABLES
Table 1.
Renal Function Categories by eGFR Ranges .............................................5
Table 2.
Criteria to Establish Stable Renal Function................................................8
Table 3.
Noncompartmental PK Parameters...........................................................12
Table 4.
PK Parameters to be Summarized Descriptively by Group......................14
LIST OF FIGURES
None.
APPENDICES
Appendix 1. SAS CODE FOR ANALYSES...........................................................................18


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PFIZER CONFIDENTIAL
1. AMENDMENTS FROM PREVIOUS VERSION(S) 
None.
2. INTRODUCTION
PF-06651600 is intended for chronic use in patients, some of whom may have some degree of 
impaired renal function. Therefore, the purpose of this study is to characterize the effect of 
renal impairment on the plasma PK of PF-06651600. Findings from this study will be used 
to develop dosing recommendations so that the dose and/or dosing interval may be adjusted 
appropriately in the presence of renal disease.
2.1. Study Design
This is a Phase 1, non-randomized, open-label, multiple-dose, parallel-cohort, multisite 
study to investigate the effect of renal impairment on the plasma PK, safety and tolerability 
of PF-06651600 after multiple oral doses of 50 mg QD. A staged approach, as outlined in 
detail below, will be followed in the study.
Participants will be selected and categorized into normal renal function or renal impairment 
groups based on their estimated glomerular filtration rate (eGFR) as shown in Table 1.
Table 1.
Renal Function Categories by eGFR Ranges
Cohort
Renal Impairmenta
Estimated eGFRb (mL/min)
Number of 
Participants
1
Severe Renal Impairment
<30 and not requiring 
dialysis
8
2
None (Normal)
≥90
8
3
Moderate renal impairment
≥30 to <60
8
4
Mild Renal Impairment
60 - 89
8
a.
Stages of renal impairment are based on Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical 
Practice Guidelines for Chronic Kidney Disease (CKD).1
b.
Estimate of eGFR based on Modification of Diet in Renal Disease (MDRD) formula. The average of the 
2 screening eGFR value will be used for group assignment.

Step 1: eGFR (mL/min/1.73m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African 
American) where Scr, std denotes serum creatinine measured with a standardized assay.

Step 2: Convert the MDRD-derived, body surface area (BSA)-adjusted eGFR obtained above to 
absolute eGFR (mL/min) for eligibility assessment using the following equation:
eGFR (mL/min) = eGFR (mL/min/1.73m2) ×participant’s BSA where BSA is calculated as
BSA= (Weight0.425 x Height0.725) × 0.007184.
Part 1: A total of approximately 16 participants will be enrolled in Part 1; approximately
8 participants with severe renal impairment and approximately 8 with normal renal function 
to ensure at least 6 evaluable participants in each group. Participants from the severe renal
impairment group will be recruited first. The demographics will be pooled across study sites 
to determine an average value for age and weight in the severe impairment group. 
Subsequently, the healthy participants will be recruited later such that each participant’s age 
is within ±10 years and weight is within ±15 kg of the mean of severe renal impairment 


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PFIZER CONFIDENTIAL
group. An attempt will be made to maintain a similar male/female ratio and racial 
composition between groups. Care will be taken when recruiting the healthy participants 
such that the entire group is not of substantially different age or of substantially different 
body weight than the renally impaired participants. Approval from the sponsor must be 
obtained before proceeding with dosing healthy participants with normal renal function 
(Cohort 2).
Participants who withdraw from the normal or severe renal impairment groups for 
non-safety related reasons and who are considered to be non-evaluable with respect to the 
primary PK objective of this study may be replaced at the discretion of the principal 
investigator (PI) and the sponsor to ensure at least 6 evaluable participants.
Criteria to proceed to Part 2: After statistical evaluation of results from Part 1 (see 
Section 9.4 in the protocol), Part 2 will be conducted if the point estimate of PF-06651600 
area under the concentration-time curve from time 0 to 24 hours (AUC0-24) geometric mean 
ratio (GMR) for the severe renal impairment group (compared to the normal group as 
control) is ≥2.0. If this criterion is not met, the study will stop after Part 1.
Part 2: Based on whether the decision criterion to proceed to Part 2 is met, approximately 
8 participants each with moderate and mild renal impairment will be enrolled to ensure at 
least 6 evaluable participants in each group. As in Part 1, renal impairment classification 
will be based on eGFR. Healthy participants will not be enrolled in Part 2.
When recruiting the Part 2 participants, attempts to match the entire group to the 
participants in Part 1 with respect to age, gender and body weight will be made. Other 
demographics, such as race and ethnicity, may be considered for matching the Part 1 and 
Part 2 populations when possible.
As in Part 1, participants who withdraw from the moderate or mild impairment groups for 
non-safety related reasons and who are considered to be non-evaluable with respect to the 
primary PK objective of this study may be replaced at the discretion of the PI and the 
sponsor to ensure at least 6 evaluable participants.
For both Parts 1 and 2: All participants in both normal and renal impairment groups will 
provide informed consent and undergo Screening evaluations to determine their eligibility. 
Participant screening for participation in this study will consist of 2 clinical research unit 
(CRU) outpatient visits not more than 14 days apart (but at least 3 days apart), with the 
1st Screening visit occurring within 28 days prior to administration of IP. Each participant 
will be admitted to the research unit on Day -1 (at least 12 hours prior to the dosing of 
PF-06651600 on Day 1). An eGFR value for group placement (provided stable renal
function is still demonstrated) will be obtained by the average of the 2 screening values 
(using the Modification of Diet in Renal Disease [MDRD] equation). If the renal function 
stability criterion is met but the renal function classification category changes between 
Screening Visit 1(S1) eGFR and the average of the S1 and Screening Visit 2 (S2) eGFRs, the 
eGFR measurement at Day -1 will also be used to determine the appropriate group 
classification category using an average of all 3 eGFR values, to determine whether the 
participant will be eligible for enrollment.


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PFIZER CONFIDENTIAL
Calculation of eGFR:  The following MDRD equation will be used to calculate eGFR (Scr, 
std denotes serum creatinine measured with a standardized assay for serum creatinine):
eGFR (mL/min/1.73 m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female)
                                          × (1.212 if African American)
Note that the value of eGFR, which is directly obtained from the lab or calculated using the
equation above, is generally normalized to an average body size of 1.73 m2 for diagnosis,
prognosis and treatment of renal disease. In terms of clearance of renally filtered drugs
(including secreted drugs), renal elimination capacity is related to absolute glomerular
filtration rate (GFR) in mL/min. To use the MDRD-derived, body surface area 
(BSA)-adjusted value of eGFR to obtain absolute glomerular filtration rate (GFR) (mL/min) 
for renal disease classification or participant assignment into different renal disease groups,
this value should be multiplied by the individual participant’s BSA (ie, measured
BSA/1.73 m2). The BSA of an individual can be calculated by the following formula as
described below:
BSA = (Weight0.425 x Height0.725) x 0.007184
In summary, GFR in mL/min calculated as below will be used for renal impairment group
placement:
Step 1: Obtain the MDRD-derived eGFR:
eGFR (mL/min/1.73 m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female)× (1.212 
if African American) where Scr, std denotes serum creatinine measured with a standardized 
assay.
Step 2: Convert the MDRD-derived, BSA-adjusted eGFR obtained above to absolute GFR
(mL/min) for eligibility assessment using the following equation:
eGFR (mL/min) = eGFR (mL/min/1.73 m2) ×participant’s BSA where BSA is calculated as 
BSA = (Weight0.425 x Height0.725) x 0.007184.
CLCR will also be estimated from a spot serum creatinine measurement using the following
Cockcroft-Gault (C-G) equation:
Note that eGFR calculated by the MDRD equation will be used for categorization of degrees
of renal impairment. Nevertheless, renal function will be estimated using both C-G and
MDRD equations in this study and dose recommendations will be made using both C-G and
MDRD equations.


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PFIZER CONFIDENTIAL
To be enrolled into the study, participant should demonstrate stable renal function, with
≤25% change based upon screening S1 eGFR and screening S2 eGFR (calculated by the
MDRD equation). The S2 eGFR assessment should be performed between 3 to 14 days after
the S1 eGFR assessment. The average of these 2 eGFR values will be used for group
placement based on the renal function classification category.
If the renal function stability criterion is met and the renal function classification category 
remains the same between S1 eGFR and the average of the S1 and S2 eGFRs, participant 
will be eligible for enrollment.
If the renal function stability criterion is not met, participant will be screen failed.
If the renal function stability criterion is met but the renal function classification category 
changes between S1 eGFR and the average of the S1 and S2 eGFRs, the eGFR measurement 
at Day -1 will also be used to determine the appropriate group classification category using 
an average of all 3 eGFR values, to determine whether the participant will be eligible for 
enrollment.
In case of screen failure related to eGFR stability and/or change in the renal function
classification category, participant may be re-screened once after a 30-day period, provided
that the initial screen failure is not due to an Inclusion/Exclusion criterion that results in
permanent disqualification from enrollment (eg, medical history). This can be done only
with Sponsor’s approval.
Table 2.
Criteria to Establish Stable Renal Function
Renal function Measurement
eGFR (mL/min)
Criterion for stability
S1
G1
S2 (Within 3 to 14 days after S1)
G2
∆=|G2-G1|×100/G1a
If ∆ ≤25%; stable
If ∆ >25%; not stable
Abbreviations: S1= Screening Visit 1; S2= Screening Visit 2.
a.
Parenthesis of | | represents absolute values.
The eGFR value will be determined on Day -1, 2, 5, 8, and 11, and the average eGFR values
from Day -1 to Day 11 will be used in PK analysis.
The total participation time (ie, CRU confinement time for study procedures) for each 
participant in this study is approximately 11 nights/12 days (excluding screening & 
Follow-Up contact). Participants will have a follow-up phone call 28-35 days after last dose 
administration to assess for AEs (Adverse Events).
A participant is considered to have completed the study if he/she has completed all phases of 
the study including the last scheduled procedure shown in the Schedule of Activities in the 
protocol.


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PFIZER CONFIDENTIAL
2.2. Study Objectives
Primary Objective

Part 1: To evaluate the effect of severe renal impairment on the PK of PF-06651600 
following multiple oral dose administration.

Part 2 (if applicable): To evaluate the effect of moderate and mild renal impairment 
on the PK of PF-06651600 following multiple oral dose administration.
Secondary Objective

To evaluate the safety and tolerability of multiple oral doses of PF-06651600 in 
participants with renal impairment and in healthy participants with normal renal 
function.
Tertiary/Exploratory Objectives

To compare additional PK parameters of PF-06651600 following administration of 
multiple oral doses in participants with renal impairment and in healthy participants 
without renal impairment.

To enable exploratory research through collection of banked biospecimens, unless 
prohibited by local regulations or ethics committee decision.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
No formal interim analysis will be conducted for this study. As this is an open-label study, 
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment.
Additionally, PK data will be analyzed in Part 1 and based on the results decision will be 
made whether to progress to Part 2.
Final analysis will follow the official database release.  As this will be an open-label study, 
there is no formal unblinding of the randomization code.
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
No hypotheses are required.
4.2. Statistical Decision Rules
After statistical evaluation of results from Part 1 (see Section 9.4 in the protocol), Part 2 will 
be conducted if the point estimate of PF-06651600 area under the concentration-time curve 
from time 0 to 24 hours (AUC0-24) geometric mean ratio (GMR) for the severe renal 
impairment group (compared to the normal group as control) is ≥2.0. If this criterion is not 
met, the study will stop after Part 1.


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5. ANALYSIS SETS
5.1. Pharmacokinetic (PK) Analysis Set
5.1.1. Concentration Analysis Set
The PK concentration population is defined as all participants assigned to investigational 
product and treated who have at least 1 concentration measured.
5.1.2. Parameter Analysis Set
The PK parameter analysis population is defined as all participants assigned to 
investigational product and treated who have at least 1 of the PK parameters of primary 
interest measured.
5.2. Pharmacodynamic Analysis Set
None.
5.3. Safety Analysis Set
All assigned to investigational product and who take at least 1 dose of investigational 
product. Participants will be analyzed according to the product they actually received.
5.4. Other Analysis Sets
None.
5.5. Treatment/Group Misallocations 
All analyses will be performed on an “as-treated” basis and will not include data from 
subjects who are randomized but not treated.
If based on eGFR value(s) a subject is assigned to the wrong renal impairment group, this 
subject will be reassigned to the correct group and analyzed for safety and PK analysis 
according to his reassigned group. 
5.6. Protocol Deviations
Subjects who experience events that may affect their PK profile (eg, lack of compliance with 
dosing) may be excluded from the PK analysis.  At the discretion of the pharmacokineticist a 
concentration value may also be excluded if the deviation in sampling time is of sufficient 
concern or if the concentration is anomalous for any other reason.
A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure.
5.6.1. Deviations Assessed Prior to Randomization
At Screening, the investigator will assess subjects against the inclusion and exclusion criteria 
as set out in Sections 4.1 and 4.2 of the protocol.


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5.6.2. Deviations Assessed Post-Randomization
A full list of protocol deviations for the study report will be compiled prior to database 
closure.  Any significant deviation from the protocol will be reviewed prior to database 
closure and a decision taken regarding evaluation for each analysis population.
6. ENDPOINTS AND COVARIATES
6.1. Efficacy Endpoint(s)
None.
6.2. Safety Endpoints
An adverse event is considered a Treatment-Emergent Adverse Event (TEAE) if the event 
started during the effective duration of treatment. 
All events that start on or after the first dosing day and time/start time, if collected, but before 
the last dose plus the lag time will be flagged as TEAEs.  
The following data are considered in standard safety summaries (see protocol for collection 
days and list of parameters):

adverse events,

laboratory data,

vital signs data,

ECG results.
6.3. Other Endpoints
6.3.1. PK Endpoints
Blood and urine samples for PK analysis of PF-06651600 will be taken according to the 
Schedule of Activities given in the protocol.
The following PK parameters will be calculated for PF-06651600 (if possible) from the 
concentration-time data using standard noncompartmental methods:


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Table 3.
Noncompartmental PK Parameters
Matrix
PK Parameter
Analysis Scale
PF-06651600
Plasma
AUC0-24
ln
A, D
AUClast
ln
D
Cmax
ln
A, D
Tmax
R
D
CL/F
ln
D
Ctrough
ln
D
Urine*
CLr
†
ln
D
Ae24
R
D
Ae24(%)
R
D
Key:
A=analyzed using statistical model, D=displayed with descriptive statistics,
ln=natural-log transformed, R=raw (untransformed), * =will be analyzed depending
on Plasma PK results.
6.3.2. PD Endpoints
None.
6.4. Covariates
None.
7. HANDLING OF MISSING VALUES
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.
7.1. Concentrations Below the Limit of Quantification
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero.  (In listings BLQ values will be reported as “<LLQ”, where LLQ 
will be replaced with the value for the lower limit of quantification).
7.2. Deviations, Missing Concentrations and Anomalous Values
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if 1 of the following cases is true:
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample).
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
7.3. Pharmacokinetic Parameters
Actual PK sampling times will be used in the derivation of PK parameters.


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If a PK parameter cannot be derived from a subject’s concentration data, the parameter will 
be coded as NC (ie, not calculated). (Note that NC values will not be generated beyond the 
day that a subject discontinues).
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular renal function group with ≥3 evaluable measurements.  For 
statistical analyses (ie, analysis of variance), PK parameters coded as NC will also be set to 
missing; and analyses will not be performed for a particular parameter if more than 50% of 
the data are NC.
If an individual subject has a known biased estimate of a PK parameter (due for example to 
an unexpected event such as vomiting before all the compound is adequately absorbed in the 
body), this will be footnoted in summary tables and will not be included in the calculation of 
summary statistics or statistical analyses.
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
8.1. Statistical Methods
The effect of the renal impairment on PK parameters will be assessed by constructing 
90% confidence intervals around the estimated difference between each of the Test (renal 
impaired groups) and the Reference (normal renal function group) using a one-way ANOVA 
model based on natural log transformed data.
The relationship between PK parameters and renal function will be assessed using linear 
regression model.
8.2. Statistical Analyses
Part 1
Analysis of variance (ANOVA) will be used to compare the natural log transformed 
PF-06651600 AUC0-24 and Cmax between normal renal function group (Reference) and the 
severe impaired renal function group (Test). Estimates of the adjusted mean differences 
(Test-Reference) and corresponding 90% confidence intervals (CIs) will be obtained from 
the model. The mean differences and 90% CIs for the differences will be exponentiated to 
provide estimates of the ratio of the geometric means (Test/Reference) and 90% CIs for the 
ratios.
Part 2 may be conducted if PF-06651600 AUC0-24 GMR for severe renal impairment group 
compared to normal group is ≥2.
Part 2
ANOVA will be used to compare the natural log transformed PF-06651600 AUC0-24 and Cmax
between normal renal function group (Reference) and the moderate and mild impaired renal 
function groups (Test). Estimates of the adjusted mean differences (Test-Reference) and 
corresponding 90% CIs will be obtained from the model. The mean differences and 90% CIs 
for the differences will be exponentiated to provide estimates of the ratio of the geometric 


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means (Test/Reference) and 90% CIs for the ratios. If substantial differences in 
demographic characteristics between healthy and impaired participants are observed, weight 
and age will be explored as covariates.
Box and whisker plots for individual participant parameters (AUC0-24 and Cmax) will be 
constructed by renal function group and overlaid with geometric means.
For summary statistics and median/mean plots by sampling time, the nominal PK sampling 
time will be used. For individual participant plots by time, the actual PK sampling time will 
be used.
If Part 2 is executed and data for normal, mild, moderate and severe impairment groups are 
available, additional analysis will be performed to assess relationship between appropriate 
PK parameters and renal function.
Linear regression will be used to analyze the potential relationship between appropriate PK 
parameters (CL/F or CLr, and VZ/F) and renal function (eGFR). Estimates of the slope and, 
intercept, together with their precision (90% CI), and the coefficient of determination will be 
obtained from the model.
Plots of PK parameters (CL/F or CLr, and VZ/F) versus renal function (eGFR) will be 
constructed. A regression line and 90% confidence region for the PK parameters and eGFR 
will be included if appropriate. Vertical lines for the renal function group cut-off values will 
also be presented on the plots. Different symbols will be used to identify participants from 
different renal function groups.
Residuals from the models will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals but these will not be included in the clinical study report. If there are major 
deviations from normality or outliers then the effect of these on the conclusions will be 
investigated through alternative transformations and/or analyses excluding outliers.  
Justification for any alternative to the planned analysis will be given in the report of the 
study.
The following PK parameters will be summarized by renal function group:
Table 4.
PK Parameters to be Summarized Descriptively by Group
Parameter
Summary Statistics
AUClast, AUC0-24, 
Cmax, Ctrough, CLr, 
CL/F 
N, arithmetic mean, median, cv%, standard deviation, 
minimum, maximum, geometric mean and geometric cv%.
Tmax
N, median, minimum, maximum.
Ae24, Ae24(%)
N, arithmetic mean, median, cv%, standard deviation, 
minimum, maximum.


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Presentations for PF-06651600 concentrations will include:
-
a listing of all concentrations sorted by renal function group (present in heading), subject 
id and nominal time postdose.  The concentration listing will also include the actual 
times.  Deviations from the nominal time will be given in a separate listing.
-
a summary of concentrations by renal function group and nominal time postdose, where 
the set of statistics will include n, mean, median, standard deviation, coefficient of 
variation (cv), minimum, maximum and the number of concentrations above the lower 
limit of quantification.
-
median concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose by renal function group (all renal function groups on the same plot per 
scale, based on the summary of concentrations by renal function group and time 
postdose).
-
mean concentrations time plots (on both linear and semi-log scales) against nominal time 
postdose by renal function group (all renal function groups on the same plot per scale,
based on the summary of concentrations by renal function group and time postdose).
-
individual concentration time plots by renal function group (on both linear and semi-log 
scales) against actual time postdose (there will be separate spaghetti plots for each renal
function group per scale).
-
a listing of all urine concentration interval sorted by renal function group (present in 
heading), subject ID and nominal collection duration postdose.
For summary statistics, median and mean plots by sampling time, the nominal PK sampling 
time will be used, for individual subject plots by time, the actual PK sampling time will be 
used.
8.3. Safety Analysis
A set of summary tables split by renal function group will be produced to evaluate any 
potential risk associated with the safety and toleration of administering PF-06651600.
8.3.1. Treatment and Disposition of Subjects
Subject evaluation groups will show end of study subject disposition and will show which 
subjects were analyzed for pharmacokinetics, as well as for safety (adverse events and 
laboratory data).  Frequency counts will be supplied for subject discontinuation(s) by renal
function group.
Data will be reported in accordance with the sponsor reporting standards.
8.3.2. Demographic and Clinical Examination Data
A break-down of demographic data will be provided for age, race, weight, body mass index, 
and height.  Each will be summarized by sex at birth and ‘All Subjects’ in accordance with 
the sponsor reporting standards.


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PFIZER CONFIDENTIAL
8.3.3. Discontinuation(s)
Subject discontinuations, temporary discontinuations or dose reductions due to adverse 
events will be detailed and summarized by renal function group.
Data will be reported in accordance with the sponsor reporting standards.
8.3.4. Adverse Events
Adverse events will be reported in accordance with the sponsor reporting standards by renal
function group.
8.3.5. Laboratory Data
The baseline measurement is the last pre-dose measurement.
Laboratory data will be listed and out of range values will be summarized in accordance with 
the sponsor reporting standards.
8.3.6. Vital Signs Data
The baseline measurement is the last planned pre-dose measurement.
Vital Signs data will be listed and out of range values will be summarized in accordance with 
the sponsor reporting standards.
8.3.7. ECG Data
The baseline measurement is the last planned pre-dose measurement.
ECG data will be listed and frequencies of out of range values will be provided in accordance 
with the sponsor reporting standards.
8.3.8. Other Safety Data
None.
8.3.9. Concomitant Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the 
listings.
8.3.10. eGFR (estimated Glomerular Filtration Rate) Data
These data will be listed and summarized by renal group and time point in accordance with 
the sponsor reporting standards.
8.3.11. Screening and Other Special Purpose Data
Screening data that will be brought in-house will be listed.


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9. REFERENCES
1.
National Kidney Foundation. (2002) K/DOQI Clinical practice guidelines for chronic 
kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 
39(2 Suppl 1):S1-266.


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10. APPENDICES
Appendix 1. SAS CODE FOR ANALYSES
An example of the PROC REG code (Applicable for Part 2) is provided below:
proc reg data=tab.pk;
model l&var=clcr/clb alpha=0.1;
ods output ParameterEstimates = param&var;
ods output FitStatistics = fit&var;
ods output ANOVA = reg&var;
run;
An example of the PROC MIXED code is provided below:
proc mixed data = tab.pk covtest alpha=0.1;
class group;
model l&var = group / S covb alpha=0.1 CL DDFM=KR;
repeated/ type=un subject=subjid group=group R;
lsmeans group;
**************Part 1*************;
estimate 'Severe vs Normal'
group 1 -1;
**************Part 2*************;
estimate 'Mild vs Normal'
group 0 -1 0 1;
estimate 'Moderate vs Normal'
group 0 -1 1 0;
ods output lsmeans = lsmeans&var;
ods output solutionf = solution&var;
run;
/* Letter assignments for group within the estimate statement above are as follows;
A = Severe (Test)
B = Normal (Reference);
C = Moderate (Test)
D = Mild (Test)  */;