Clinical trial NCT03034057
Conditions: Contraception
Sponsor: Pfizer
Start date: 2017-08-23; Completion date: 2018-12-07
Enrollment: 169 participants; Allocation: ; Intervention model: PARALLEL

Brief summary:
A one-year evaluation of Sayana Press self injection in women of reproductive age in the United Kingdom (UK).

Detailed description:

Arms: arm 1: single arm
Interventions: intervention 1: Sayana Press
Intervention descriptions: intervention 1: Sayana Press in the Uniject injection system

Protocol documents:
Prot_001.pdf: 
Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 1
PHASE IV OPEN LABEL SINGLE GROUP ONE YEAR STUDY OF HOME 
SELF-INJECTION WITH SAYANA® PRESS IN ADULT WOMEN OF 
REPRODUCTIVE AGE- A PRAGMATIC CLINICAL TRIAL
Medicinal Product Number:
PN-008839
Medicinal Product Name:
Sayana® Press (Depot 
-medroxyprogesterone Acetate)
United States (US) Investigational New 
Drug (IND) Number:
Not Applicable (N/A)
European Clinical Trials Database 
(EudraCT) Number:
2017-000051-13
Protocol Number:
A6791040
Phase:
Phase 4


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 2
Document History
Document
Version Date
Summary of Changes
Original Protocol
26 January 2017
Not applicable (N/A)


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 3
TABLE OF CONTENTS
APPENDICES ...........................................................................................................................6
PROTOCOL SUMMARY.........................................................................................................7
SCHEDULE OF ACTIVITIES................................................................................................11
1. INTRODUCTION ...............................................................................................................13
1.1. Mechanism of Action..............................................................................................13
1.2. Background and Rationale ......................................................................................13
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................14
2.1. Objectives................................................................................................................14
2.2. Endpoints.................................................................................................................15
3. STUDY DESIGN.................................................................................................................17
4. SUBJECT SELECTION......................................................................................................18
4.1. Inclusion Criteria.....................................................................................................18
4.2. Exclusion Criteria....................................................................................................19
4.3. Randomization Criteria ...........................................................................................20
4.4. Lifestyle Guidelines ................................................................................................20
4.5. Investigator Approval for Self-Injection.................................................................20
4.6. Sponsor’s Qualified Medical Personnel..................................................................20
5. STUDY INTERVENTION..................................................................................................21
5.1. Allocation to Treatment ..........................................................................................21
5.2. Subject Compliance.................................................................................................21
5.3. Study Drug Supplies................................................................................................22
5.3.1. Dosage Form(s) and Packaging..................................................................22
5.3.2. Preparation and Dispensing........................................................................22
5.3.3. Administration............................................................................................22
5.4. Study Drug Storage .................................................................................................23
5.5. Study Drug Accountability......................................................................................24
5.6. Destruction of Study Drug Supplies........................................................................24
5.7. Concomitant Treatment(s).......................................................................................24
6. STUDY PROCEDURES .....................................................................................................24


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 4
6.1. Screening (Days -14 to 1)........................................................................................24
6.2. Study Period ............................................................................................................25
6.3. Health Professional Questionnaire at the End of the Study ....................................27
6.4. Subject Withdrawal.................................................................................................27
7. ASSESSMENTS..................................................................................................................28
7.1. Pregnancy Testing...................................................................................................28
7.2. Assessments Questionnaires ...................................................................................28
7.3. Safety Assessments .................................................................................................29
8. ADVERSE EVENT REPORTING......................................................................................31
8.1. Adverse Events........................................................................................................31
8.2. Reporting Period .....................................................................................................31
8.3. Definition of an Adverse Event...............................................................................32
8.4. Medication Errors....................................................................................................32
8.5. Abnormal Test Findings..........................................................................................33
8.6. Serious Adverse Events...........................................................................................33
8.6.1. Protocol-Specified Serious Adverse Events...............................................34
8.6.2. Potential Cases of Drug-Induced Liver Injury............................................35
8.7. Hospitalisation.........................................................................................................36
8.8. Severity Assessment................................................................................................37
8.9. Causality Assessment..............................................................................................37
8.10. Exposure During Pregnancy..................................................................................38
8.11. Withdrawal Due to Adverse Events (See Also the Section on Subject 
Withdrawal)...............................................................................................................39
8.12. Eliciting Adverse Event Information ....................................................................39
8.13. Reporting Requirements........................................................................................39
8.13.1. Serious Adverse Event Reporting Requirements .....................................39
8.13.2. Non-serious Adverse Event Reporting Requirements..............................40
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 5
8.13.3. Medical Device Complaint Reporting Requirements...............................40
8.13.4. Sponsor’s Reporting Requirements to Regulatory Authorities ................40
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................41
9.1. Sample Size Determination.....................................................................................41
9.2. Statistical Methods ..................................................................................................41
9.2.1. Analysis of Primary Endpoint ....................................................................41
9.2.2. Analysis of Secondary Endpoint ................................................................42
9.2.5. Safety Analysis ...........................................................................................43
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................44
11. DATA HANDLING AND RECORD KEEPING .............................................................44
11.1. Case Report Forms/Electronic Data Record .........................................................44
11.2. Record Retention...................................................................................................44
12. ETHICS..............................................................................................................................45
12.1. Institutional Review Board/Ethics Committee......................................................45
12.2. Ethical Conduct of the Study ................................................................................45
12.3. Subject Information and Consent..........................................................................46
12.4. Subject Recruitment ..............................................................................................46
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................46
13. DEFINITION OF END OF TRIAL...................................................................................47
13.1. End of Trial in a Member State.............................................................................47
14. SPONSOR DISCONTINUATION CRITERIA ................................................................47
15. PUBLICATION OF STUDY RESULTS..........................................................................47
15.1. Communication of Results by Pfizer ....................................................................47
15.2. Publications by Investigators ................................................................................47
16. REFERENCES ..................................................................................................................49
CCI
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 6
APPENDICES
Appendix 1. Abbreviations......................................................................................................50
Appendix 2. Instructions for Use.............................................................................................52
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 7
PROTOCOL SUMMARY
Background
Intramuscular (IM) depot medroxyprogesterone acetate (DMPA), 104 mg 
medroxyprogesterone acetate (MPA) in 0.65 mL suspension for injection, has been marketed 
for many years as DEPO-PROVERA®. A new, low dose formulation for subcutaneous (SC)
injection of depot medroxyprogesterone acetate (DMPA-SC) has been approved by 
regulatory agencies for the prevention of pregnancy in women. DMPA-SC is available in
pre-filled syringes and is administered by SC injection to the anterior thigh or abdomen, once
every 3 months (13 weeks +/- 1 week).
For many years, the syringe has been the standard way to deliver solutions and suspensions
for parenteral use. The syringe design, however, is relatively bulky and the potential to 
attempt re-use of syringes increases the risk of transmission of blood borne diseases.
The Uniject™delivery system is a simple single use prefilled injection system designed for 
SC injections and has been approved for use as a contraceptive under the name Sayana®
Press.
Study Objectives and Endpoints
Primary Objectives
•
Determine the proportion of women who are able to self-inject Sayana Press 
successfully over a 1-year period.
Secondary Objectives
•
Assess continuation rate for the method at 1 year.
 
 
 
 
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 8
Primary Endpoint
The primary endpoint will be the proportion of all attempted home self-injections that were 
successfully performed by the study participant at home (ie, not in the clinic under direct 
HCP supervision) and on schedule (13 week interval +/- 1 week).  If a subject decides to 
discontinue Sayana Press as her contraceptive method, and therefore does not attempt one or 
more injections, these scheduled injections would not be included in the denominator for the 
primary endpoint.
Secondary Endpoint
•
Continuation rate for method at 1 year.
 
 
 
 
 
 
 
 
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 9
•
HCP Questionnaire:
•
Percentage of suitable patients, based on Question 1;
•
Percentage of willing patients, based on Question 2;
•
Usefulness of training materials, based on Question 3;
•
Ease to teach a patient to self-inject, based on Question 4;
•
Overall experience/other information and input, based on Questions 5, 6 and
7.
 
 
Safety Analysis
Safety data, consisting of all adverse events, including unplanned pregnancies, persistent 
injection site reactions, SAEs, premature discontinuations, concomitant medications, vital 
signs, height and weight, and laboratory parameters, will be tabulated and listed according to 
Pfizer’s standard reporting algorithms.
Study Design
This is an open-label, single-arm, 1-year study to assess home self-administration of Sayana 
Press in women who desire long-acting reversible contraception (LARC), are interested to 
attempt DMPA self-injection at home and are judged by their HCP to be good candidates for 
self-injection.  Following training and a supervised initial self-injection at the clinic, study 
participants will self-inject Sayana Press in the home setting every 3 months (at Month 3, 
Month 6 and Month 9) and return for a final study visit at Month 12.
Approximately 160 adult women subjects of reproductive age (18 to 45) will be enrolled to 
ensure that at least 100 women will complete the study.
Participants will attend 2 or 3 study visits at the clinic: a Screening/Baseline Visit or 
Screening and Baseline visit separately and a Final Visit.  At Months 3, 6 and 9, participants 
will be asked to contact the clinic by phone after performing each scheduled home 
self-injection in order to confirm the date of injection and to report any AEs, and/or injection 
difficulties or problems with the device.  Should the injection site reactions occur, the centre
staff will collect detailed information about these reactions.  Reasons for self-injection failure 
will also be recorded in the case report form (CRF).
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 10
At the Month 12 Final Visit or premature discontinuation, subjects will be asked to complete 
the 
 
 
 
 
 
If an unplanned pregnancy occurs during the trial it will be collected on the AE Case Report 
Form (CRF) page.
Statistical Analysis
As this is a single arm study, there will be no treatment comparisons, and all analyses will be 
descriptive. 
The primary endpoint is the mean percent of self-injections that were successfully 
administered.  Each subject will have a maximum of 3 self-injections, each of which will be 
defined as a success or failure.  A success is defined as a home self-injection that was 
successfully performed by the study participant at home and on schedule (13 week interval 
+/- 1 week).  If the subject attempts but is unable to administer the self-injection at home and 
had it performed instead at the clinic, then these are classed as failures.  If a subject 
discontinues from the study prior to attempting all 3 injections, or chooses not to attempt the 
injection at home, but have it performed in the clinic, then only the injections that were 
attempted at home will be evaluated and included in the analysis.  These binary outcomes are 
correlated within the subject, and they will therefore be analyzed with a generalized 
estimating equation (GEE) model for clustered binomial data, using subject as the clustering 
variable, to provide a proportion along with 95% confidence interval.
The secondary endpoint is the continuation rate for the method at 1 year.  Subjects had 
completed 12 months if they received all 4 injections, had a follow-up visit and were not 
recorded as discontinuing during the 12 month period.  The total proportion of subjects who 
have not discontinued by 12 months (the follow-up visit) will be estimated along with a 95% 
confidence interval (CI).
Endpoints from the questionnaires will be summarized either as categorical frequencies by 
counts and percentages.
Safety data will be tabulated and listed according to Pfizer’s standard reporting algorithms.
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 11
SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  
Refer to the Study Procedures and Assessments sections of the protocol for detailed 
information on each procedure and assessment required for compliance with the protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities, in order to conduct evaluations or assessments required to protect the 
well-being of the subject.
Visit Identifier
Protocol Activity
Screening 
(Days 
-14 to 1)
Baseline  
(Day 1)
Month 3
(Subject 
Phone 
Assessment)
Month 6
(Subject 
Phone 
Assessment)
Month 
9 (Subject 
Phone 
Assessment)
Final Visit 
(Month 12)
or PDf
Informed Consent
X
General Medical History 
X
General Physical 
Examination
X
X
Demography
X
Weight and Height
X
X
Vital Signs (sitting Blood 
Pressure [BP], Heart Rare 
[HR]
X
X
X
Urine Pregnancy Test
X
X
X
Pregnancy Test (If 
Self-Injection is
Delayed)g
X
X
X
Registration in Study
X
Record Subject’s 
Educational Level
X
Self-injection Training 
(including first 
self-injection and 
recording problems with 
the device, if any)
X
Investigator Approval of 
Self-injection Proficiency
X
Drug Dispensing
X
Adverse Eventsh
X
X
Xa
Xa
Xa
X
Self-Injection at Home
X
X
X
Self-Report Injection 
Difficulties or Problems 
with the Device
Xa
Xa
Xa
Priorb/Concomitant 
X
X
X
X
X
X


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 12
Medicationsc
End of Studye
X
Abbreviations:  Pharmacodynamic (PD), Blood Pressure (BP), Heart Rate (HR), 
a.
At Months 3, 6 and 9, participants will be asked to contact the clinic by phone after performing each 
scheduled self-injection in order to confirm the date of injection, report any adverse events and/or injection 
difficulties or problems with the device, including injection site reactions, and unplanned pregnancy. If at 
least 1 week has passed from the scheduled self-injection date and the clinic has not heard from the subject, 
the clinic staff will contact the subject to obtain the necessary information and provide appropriate 
instructions to the subject.  Reasons for self-injection failure will also be recorded in the CRF.
b.
Prior/current medications for the 2-week period prior to Baseline Visit.
c.
Concomitant medications taken after first administration of study drug.
d.
 
 
e.
End of study form and study drug accountability.
f.
Premature Discontinuation visit.
g.
Whenever a scheduled injection has been delayed beyond the protocol-specific window (scheduled 
injection date ± 1 week), the subject should be advised to contact the clinic and speak to a healthcare 
professional regarding the need to exclude pregnancy before any additional injections, advice regarding 
additional contraception, and also for the timing of the next injection.  A pregnancy test is to be conducted 
if the Sayana Press injection is delayed outside the protocol study drug administration window.  This could 
be either a home pregnancy test or test conducted in the clinic.  If the subject has a positive pregnancy test 
result, she is not to inject Sayana Press and must inform the study centre immediately, to conduct a final 
study visit (subject will be prematurely terminated).  The study centre must complete and submit an
Exposure During Pregnancy Form to Pfizer within 24 hours of awareness of the pregnancy.  The study 
centre will follow all protocol required pregnancy in utero procedures (See Section 8.10). 
h.
AEs (serious and non-serious) should be recorded on the case report form (CRF) from the time the subject 
has taken at least 1 dose of investigational product through the last subject visit.
CCI
CCI
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 13
1. INTRODUCTION
1.1. Mechanism of Action
Medroxyprogesterone acetate (MPA) is a synthetic analogue of 17 -hydroxyprogesterone, 
which has antioestrogenic, anti-androgenic, and anti-gonadotropic effects.  MPA inhibits the 
secretion of gonadotropins which, in turn, prevents follicular maturation and ovulation.  The 
primary mechanism for MPA’s contraceptive effect is suppression of ovulation.  Secondary 
mechanisms, which may also aid the contraceptive effect, include endometrial thinning and 
thickening of the cervical mucus. 
1.2. Background and Rationale
Intramuscular (IM) depot medroxyprogesterone acetate (DMPA), 104 mg 
medroxyprogesterone acetate (MPA) in 0.65 mL suspension for injection, has been marketed 
for many years as DEPO-PROVERA®. A new, low dose formulation for subcutaneous (SC)
injection of depot medroxyprogesterone acetate (DMPA-SC) has been approved by 
regulatory agencies for the prevention of pregnancy in women. DMPA-SC is available in
pre-filled syringes and is administered by SC injection to the anterior thigh or abdomen, once
every 3 months (13 weeks +/- 1 week).
For many years, the syringe has been the standard way to deliver solutions and suspensions
for parenteral use. The syringe design, however, is relatively bulky (especially if pre-filled
with drug) and the potential to attempt re-use of syringes increases the risk of transmission of 
blood borne diseases.
The Uniject™delivery system is a simple single use prefilled injection system designed for 
IM and SC injections. Uniject was originally developed by the international non-profit 
organization Program for Appropriate Technology in Health (PATH) and the device is 
manufactured by Becton, Dickinson and Co. DMPA-SC in the Uniject™is now approved in 
a number of countries and is available as Sayana® Press.  In Europe, Sayana Press has been 
recently (July 2015) approved under the Mutual Recognition Procedure (MRP) to allow
women the option of home self-injection, when this option is considered appropriate by their 
physician; the Medicines and Healthcare products Regulatory Agency (MHRA) have granted 
approval for this variation in the United Kingdom (UK).
Several studies by independent researchers have evaluated the feasibility and acceptability of 
self-injected DMPA-SC.1 -5 Overall, women who performed self-injections in these studies 
found DMPA-SC self-injection to be easy and convenient and would recommend the method 
to other women.  These independent studies also support home-based self-administration of 
DMPA-SC.
The approval of self-injection with Sayana Press was primarily based on a 1-year 
investigator-initiated study (Cameron, et al Study GA678152) that used Sayana (DMPA-SC 
in a pre-filled syringe) and a usability study that used Sayana Press (DMPA-SC in Uniject™)
in which participants (volunteers) performed simulated injections into an injection trainer and 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 14
assessed the functionality or usability of the device and the instructions for use for the device.  
While the GA67815 study showed that women can perform independent (at home) 
self-injection when using the pre-filled syringe, the Uniject™device is fundamentally 
different to the syringe and MHRA has identified a need for a post-approval study that shows 
that women can similarly self-inject successfully when using the Uniject™device rather than 
a standard pre-filled syringe.
This study is intended to provide information on the use of Sayana Press by women who 
self-inject the product at home over a 1-year period as part of Post Authorization Safety 
Study (PASS) required by MHRA. 
This protocol and study procedures are intended to mirror standard clinical practice as 
closely as possible in order to provide information that is most relevant to the use of Sayana
Press in the community. 
The most important positive aspect of self-injection is that it is simply convenient for the
patient.  The potential risks of permitting home self-injection include a concern for the 
timeliness of injection.  With self-administration on such an infrequent schedule (every
3 months), it is possible the patient will forget to administer the injection and could
experience a contraceptive failure.  It is a certainty that some patients will not be timely, but 
DMPA is rather forgiving in this respect.  One of the characteristics of this Long Acting 
Reversible Contraception (LARC) is that the return to fertility, after stopping treatment, 
generally takes at least 6 months and often up to a year.  The reminder techniques should be 
used to ensure subjects would to maintain their scheduled administrations at home.  The 
other principal risk with unsupervised self-injection is that the woman will be unable to
properly perform the injection. The availability of effective training materials and other aids 
will be important to achieving this goal.  It should be noted, that a patient who is unable to 
demonstrate proficiency in the clinic should not be considered as a candidate for 
self-injection.
In consideration of all the above factors, the benefit-risk profile for permitting self-injection
by suitably selected and trained patients is favorable.
Complete information for this compound may be found in the single reference safety 
document (SRSD), which, for this study, is the current approved Summary of Product 
Characteristics (SmPC) for Sayana Press.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
Primary Objectives

Determine the proportion of women who are able to self-inject Sayana Press 
successfully over a 1-year period.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 15
Secondary Objectives
Assess continuation rate for the method at 1 year.
 
 
 
 
2.2. Endpoints
Primary Endpoint
The primary endpoint will be the proportion of all attempted home self-injections that were 
successfully performed by the study participant at home (ie, not in the clinic under direct 
HCP supervision) and on schedule (13 week interval +/- 1 week).  If a subject decides to 
discontinue Sayana Press as her contraceptive method, and therefore does not attempt 1 or 
more injections, these scheduled injections would not be included in the denominator for the 
primary endpoint.
Secondary Endpoint
•
Continuation rate for method at 1 year.
CCI
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 16
•
Ease of self-injection, based on Question 10 of Subject Questionnaire (including any 
post-baseline self-injections that were performed under HCP supervision, which 
would not have been included in the primary analysis);
•
Usefulness and type of reminder techniques used, based on Questions 5 and 6 of 
Subject Questionnaire;
•
Proportion of attempted home self- injections where subject returned to clinic for the 
injection (to be administered by the a HCP or under supervision of one);
•
Evaluate end of study plasma concentration of MPA;
•
Reasons for electively discontinuing self-injection of Sayana Press (where the subject 
elects to continue to receive DMPA administered by a HCP at the clinic), based on 
Question 17 of Subject Questionnaire;
•
Reasons for electively discontinuing Sayana Press altogether, based on Question 
18 of Subject Questionnaire;
•
Adverse Events (AEs), including unplanned pregnancy and persistent injection site 
reactions;
•
Other information provided in Subject Questionnaire;
•
HCP Questionnaire:
•
Percentage of suitable patients, based on Question 1;
•
Percentage of willing patients , based on Question 2;
•
Usefulness of training materials, based on Question 3;
•
Ease to teach a patient to self-inject, based on Question 4;
•
Overall experience/other information and input, based on Questions 5, 6,
and 7
 
 
Safety Analysis
Safety data, consisting of all adverse events, including unplanned pregnancies, persistent 
injection site reactions, SAEs, premature discontinuations, concomitant medications, vital 
signs, height and weight, and laboratory parameters, will be tabulated and listed according to 
Pfizer’s standard reporting algorithms.
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 17
The study will be registered in the European Union (EU) in the EU Clinical Trials Register 
and in the United States in the ClinicalTrials.Gov registry, according to local requirements. 
3. STUDY DESIGN
This is an open-label, single-arm, 1-year study to assess home self-administration of Sayana
Press in women who desire long-acting reversible contraception (LARC), are interested to 
attempt DMPA self-injection at home and are judged by their HCP to be good candidates for 
the self-injection option.  Following training and a supervised initial self-injection at the 
clinic, study participants will self-inject Sayana Press in the home setting every 3 months (at 
Month 3, Month 6 and Month 9) and return for a final study visit at Month 12.
Approximately one hundred sixty (160) adult women subjects of reproductive age (18 to 45)
will be enrolled at approximately 10 study centres in the UK (and other countries in Europe if 
required) with approximately 16 subjects per study centre, to ensure that at least 100 women 
will complete the study.
Participants will attend 2 or 3 study visits at the clinic: a Screening/Baseline Visit (or 
Screening and Baseline visits separately) and a Final Visit. At Months 3, 6 and 9, 
participants will be asked to contact the clinic by phone after performing each scheduled 
home self-injection in order to confirm the date of injection and to report any AEs, and/or 
injection difficulties or problems with the device.  Should the injection site reactions occur,
the centre staff will collect detailed information about these reactions. If at least 1 week has 
passed from the scheduled self-injection date and the clinic has not heard from the subject, 
the clinic staff will contact the subject to obtain the necessary information and provide 
appropriate instructions to the subject, depending on the circumstances.  All AEs, including 
pregnancy and injection site reactions will be recorded on the AE Case Report Form (CRF)
page.  Reasons for self-injection failure will also be recorded in the CRF.
At the Month 12 Final Visit or Premature Discontinuation, subjects will be asked to complete 
the 
 
 
 
 
 
If a subject does not perform a scheduled self-injection at home for any reason, the subject 
should immediately contact the clinic to explain the reason why the injection was not 
performed.  The HCP at the clinic must provide instructions to the subject regarding how the 
scheduled injection will be provided: 
•
An unscheduled visit will need to be conducted if the subject would prefer to have the 
scheduled injection performed at the clinic.  If so, additional training in the 
self-injection technique should be provided to the subject during the unscheduled 
visit.
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 18

If the reason why the self-injection did not occur was due to malfunction or damage 
to the Sayana Press injector, a replacement Sayana Press injector should be provided 
to the subject at the unscheduled visit to replace it and the subject should self-inject 
immediately upon returning home.

If the subject did not self-inject at home due to desire to discontinue participation in 
the study, they should complete the final/premature discontinuation visit assessments.  
If the subject prematurely discontinues from the study, another contraceptive method 
should be prescribed to the subject.
Whenever a scheduled injection has been delayed beyond the protocol-specified window 
(scheduled injection date ±1 week), the subject should be advised to contact the clinic and 
speak to a healthcare professional regarding the need to exclude pregnancy before any 
additional injections, advice regarding additional contraception, and also for the timing of the 
next injection.  A pregnancy test should also be conducted prior to the next scheduled 
injection.
The study centres will record any instances where a study participant was unable to 
self-inject at home and needed to make an unscheduled clinic visit in order to receive the 
injection (irrespective of who performs the injection at the clinic: self-injected or 
HCP-injected).
If an unplanned pregnancy (lack of efficacy) occurs during the trial it will be collected on the 
AE CRF page.  All adverse safety events will be collected and reported in the normal 
manner, according to Pfizer standard safety reporting procedures for clinical trials.
Details regarding subject self-injection issues and reasons for self-injection failure must be 
documented in the subject’s primary source records.
4. SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for the protocol intervention is considered 
appropriate by their healthcare provider. 
4.1. Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Women aged 18 to 45 years of age who are willing to attempt Sayana Press self-injection 
at home;
2. Women who are likely to be successful on a DMPA self-injection program, based on the 
opinion of the investigator;


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 19
3.
Not planning to move out of the area for at least 12 months;
4. Willing to be contacted by the clinic staff at work or at home;
5. Evidence of a personally signed and dated Informed Consent Document (ICD) indicating 
that the subject has been informed of all pertinent aspects of the study;
6. Subjects who are willing and able to comply with scheduled visits, treatment plan and 
other study procedures.
4.2. Exclusion Criteria
Subjects presenting with any of the following will not be included in the study:
1. A preexisting medical condition that would interfere with participation in the study or 
pose a risk to the subject, including hypersensitivity to MPA or any constituents of 
Sayana Press;
2. Known or suspected malignancy of genital organs;
3. Known or suspected malignancy of the breast;
4. History of cerebrovascular disease;
5. Metabolic bone disease;
6. A contraindication to DMPA (UK Medical Eligibility Criteria – Category 3 or 4),6 such 
as:

Multiple risk factors for cardiovascular disease (eg, older age, smoking, diabetes, 
obesity hypertension)

Current and history of ischaemic heart disease

Stroke (history of cerebrovascular accident, including transient ischaemic attack)

Unexplained vaginal bleeding

Current or history of breast cancer

Diabetic nephropathy, neuropathy, retinopathy or other diabetic vascular disease

Severe (decompensated) liver cirrhosis 

Hepatocellular adenoma

Hepatoma

Systemic Lupus Erythematosus (positive or unknown antiphospholipid 
antibodies; severe thrombocytopenia)


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 20
7. Subjects who are investigational centre staff members directly involved in the conduct of 
the study and their family members, centre staff members otherwise supervised by the 
investigator, or subjects who are Pfizer employees directly involved in the conduct of the 
study;
8. Participation in other studies involving investigational drug(s) (Phases 1-4) within 
30 days prior to study entry and/or during study participation;
9. Patients who plan to get pregnant within two years of study;
10. Breastfeeding female subjects and pregnant female subjects;
11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality 
that may increase the risk associated with study participation or study drug administration 
or may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the subject inappropriate for entry into this study.
4.3. Randomization Criteria
This will be a single-arm, non-randomized study.
4.4. Lifestyle Guidelines 
All subjects in this study will be women, aged 18-45, who are willing to use Sayana Press at 
home. Study subjects will self-inject Sayana Press at home according to study schedule 
(13 week interval +/- 1 week).  If the subject fails to self-inject or report to clinic for an 
injection (supervised or administered by HCP) within this +/- 1 week treatment window, she 
should be advised to use a barrier method of contraception as instructed by the study 
investigator until she administers the next injection or, in cases when the subject decides to 
discontinue Sayana Press altogether, until the new contraceptive regimen is established.  A 
pregnancy test should also be conducted prior to the next scheduled injection.
4.5. Investigator Approval for Self-Injection
Subjects who meet all inclusion criteria and none of the exclusion criteria will undergo 
training in self-injection at the Baseline Visit which will culminate in the subject attempting 
to perform the first self-injection of Sayana Press under the supervision of the investigator (or 
suitable designee).  At this point, the investigator will approve (or not approve) the subject to 
go forward in the study and be permitted to attempt the 3 subsequent self-injections at home, 
based on the investigator’s assessment of the subject’s proficiency at self-injection.  Subjects 
who are not approved for self-injection at this point will be discontinued from the study.
4.6. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 21
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational compound identifiers, subject study numbers, 
contact information for the investigational centre, and contact details for a contact centre in 
the event that the investigational centre staff cannot be reached to provide advice on a 
medical question or problem originating from another healthcare professional not involved in 
the subject’s participation in the study. The contact number can also be used by 
investigational staff if they are seeking advice on medical questions or problems; however, it 
should be used only in the event that the established communication pathways between the 
investigational centre and the study team are not available. It is therefore intended to 
augment, but not replace, the established communication pathways between the 
investigational centre and the study team for advice on medical questions or problems that 
may arise during the study. The contact number is not intended for use by the subject 
directly, and if a subject calls that number, he or she will be directed back to the 
investigational centre.
5. STUDY INTERVENTION
For the purposes of this study, and per International Conference on Harmonization (ICH)
guidelines study drug is defined as a pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in a clinical trial, including a product with a marketing 
authorization when used or assembled (formulated or packaged) in a way different from the 
approved form, or when used for an unapproved indication, or when used to gain further 
information about an approved use (ICH E6 1.33).  Study drug in this study will be the 
currently marketed, commercial Sayana Press. 
5.1. Allocation to Treatment
This is a non-randomized single arm study and all study subjects will be receiving the same 
treatment.
5.2. Subject Compliance
To document compliance, study participants will be asked to contact the clinic by phone after 
performing each scheduled self-injection in order to confirm the date of injection.  If at least 
1 week has passed from the scheduled self-injection date and the clinic has not heard from 
the subject, the clinic staff will contact the subject to obtain the necessary information and 
provide appropriate instructions to the subject, depending on the circumstances.
The investigator will provide training to the study subjects regarding the safe and correct use 
of Sayana Press according to standard of care, using currently available training materials 
that will include tools designed to facilitate the training of subjects in self-injection and that 
assist subjects in remembering the scheduled injection dates.  Since this study is intended to 
be relevant to clinical practice, and with respect to materials intended to remind study 
subjects of the proper injection date (reminder materials), Investigators should use reminder 
materials and techniques that may be employed in their practice for patients using 3-monthly 
DMPA (eg, an appointment card or reminder phone call or other electronic methods for 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 22
reaching out to patients to encourage compliance with the standard DMPA 3-monthly visit 
schedule).
5.3. Study Drug Supplies
5.3.1. Dosage Form(s) and Packaging
Sayana® Press delivery system is commercially available.  The sponsor will centrally supply 
this product to be used in accordance with local regulations and according to the commercial 
usage instructions.
5.3.2. Preparation and Dispensing
See the included commercial package leaflet for instructions on how subjects will administer 
the study drug.  Each unit will be individually packaged in single-use foil pouches.  The 
pouches should not be opened until the study drug is to be administered.  Each subject will 
receive enough product units to cover the required number of doses for the length of the 
study. 
5.3.3. Administration
The product will be administered in accordance with the label.
Study participants will be taught how to self-administer Sayana Press by the investigator or 
study centre staff using the training materials used according to standard of care in their 
practice, which are based on the approved Instructions for Use (IFU) for Sayana Press 
(Appendix 2).  If the subject is comfortable attempting the Baseline Visit self-injection, the 
first self-injection will be performed at the clinic under the supervision of the study centre
staff.  If the subject adequately performs the first self-injection, and the investigator approves 
the subject to continue in the study, based on the subject’s proficiency exhibited during the 
first self-injection, the subject will be then provided with 3 Sayana Press delivery system
packages to take home. Subjects will be also given a copy of the Sayana Press IFU and 
contact information for the clinic.  Subjects may also be given a reminder card or other 
reminder tools at the discretion of the Investigator.
If a self-injection did not occur due to malfunction or damage to the Sayana Press injector, a 
replacement Sayana Press injector should be provided to the subject at an unscheduled visit 
to replace it and the subject should self-inject immediately upon returning home.
If a scheduled injection is been delayed beyond the protocol-specified window (scheduled 
injection date ±1 week), the subject should be advised to contact the clinic and speak to a 
healthcare professional regarding the need to exclude pregnancy before any additional 
injections, advice regarding additional contraception, and also for the timing of the next 
injection.  A pregnancy test should also be conducted prior to the next scheduled injection.
Details regarding subject self-injection issues and reasons for self-injection failure must be 
documented in the subject’s primary source records.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 23
Following self-injection, the used Sayana Press injector should be immediately disposed of 
into a suitable container in accordance with the local regulatory authority requirements or per 
instructions from the Investigator.
5.4. Study Drug Storage 
The investigator, or an approved representative, eg, pharmacist, will ensure that all study 
drugs are stored in a secured area with controlled access under required storage conditions 
and in accordance with applicable regulatory requirements.
Study Drug should be stored in its original container and in accordance with the label.  See 
the Summary of Product Characteristics for storage conditions of the product.  Storage 
conditions stated in the SRSD will be superseded by the storage conditions stated in the 
labeling.
Centre systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all centre storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study on all business 
days.  Even for continuous monitoring systems, a log or centre procedure that ensures active 
daily evaluation for excursions should be available.  The operation of the temperature 
monitoring device and storage unit (for example, refrigerator), as applicable, should be 
regularly inspected to ensure it is maintained in working order. 
Any excursions from the product label storage conditions should be reported upon discovery.  
The centre should actively pursue options for returning the product to the storage conditions, 
as soon as possible.  Deviations from the storage requirements, including any actions taken, 
must be documented and reported to the sponsor.  Once an excursion is identified, the study 
drug must be quarantined and not used until the sponsor provides documentation of 
permission to use the investigational product.  It will not be considered a protocol deviation if 
the sponsor approves the use of the study drug after the temperature excursion. Use of the 
investigational product prior to sponsor approval will be considered a protocol deviation.
Specific details regarding information the centre should report for each excursion will be 
provided to the centre.
Centre staff will instruct subjects on the proper storage requirements for take home study 
drugs including how to report temperature excursions.  In the event of any significant 
temperature changes (eg, left study drug in a hot car for several hours) after the subject takes 
the study drug home from the study centre, the subject is not to use this study drug and 
should contact the study centre immediately to return that study drug and obtain a 
replacement supply.  The study centre will quarantine any study drug that was returned by a 
subject due to significant temperature changes and not redispense it. 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 24
5.5. Study Drug Accountability 
The investigative centre must maintain adequate records documenting the receipt, use, loss, 
or other disposition of the study drug supplies.  All unused study drug product will be 
returned to the investigator by the subject upon completion of the study or discontinuation.
5.6. Destruction of Study Drug Supplies 
The sponsor or designee will provide guidance on the destruction of unused study drug (eg, 
at the centre).  If destruction is authorized to take place at the study centre, the investigator 
must ensure that the materials are destroyed in compliance with applicable environmental 
regulations, institutional policy, and any special instructions provided by Pfizer, and all 
destruction must be adequately documented.
5.7. Concomitant Treatment(s)
Medications that are contraindicated with Sayana Press (as per current prescribing 
information) will be prohibited.
6. STUDY PROCEDURES 
6.1. Screening (Days -14 to 1)
Screening visit may take place on the same day as Baseline Visit or on a different day (within 
14 days prior to Baseline Visit).
The investigator (or an appropriate designee) will obtain written informed consent from each 
participant in accordance with the approved ICD.  Participants will be screened prior to 
enrollment to confirm that they meet the enrollment criteria for the study.  The following 
screening procedures will be performed:

Written, informed consent obtained prior to performance of any testing, examination 
or treatment;

Medical history;

Demographics

AE assessment;

Prior medications;

Physical examination;

Vital signs (sitting blood pressure and heart rate);

Urine pregnancy test.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 25
6.2. Study Period
Baseline Visit (Day 1)
Baseline Visit may take place on the same day as Screening Visit or on different days.
Following procedures will be performed at this visit:

Registration in the study;

AE assessment;

Vital signs (sitting blood pressure and heart rate);

Height and Weight;

Prior medications for the 2-week period prior to Baseline Visit;

Urine pregnancy test;

Record subject’s educational level;

Self-injection training including first self-injection;
The baseline training and patient-directed training materials given to study 
participants will be those used according to standard of care for patients in their
practice. 
The training materials should include suggested methods for remembering the 
scheduled injection dates per standard of care.  Investigators may also utilize patient
reminder techniques in this study that align closely with techniques they normally use
in their practice for women receiving DMPA injections every 3 months in the clinic 
(eg, an appointment card, phone call, text message or other electronic methods for 
reaching out to patients to encourage compliance with the standard DMPA 3-monthly 
visit schedule).  However, under this protocol investigators are not required to utilize 
any such outreach method to encourage compliance.  Because training techniques, 
training materials and reminder techniques might differ from centre to centre, such 
methods and the way they were delivered will be documented for each centre;

Injection difficulties or any problems with the device will be recorded in the CRF;

Investigator approval of self-injection proficiency;
Three packages containing Sayana Press delivery system will be distributed to each study 
subject for home self-injection.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 26
Months 3, 6 and 9 (subject phone assessment)
Study subjects will self-inject Sayana Press at home according to schedule (13 week interval 
+/- 1 week).  They will be asked to contact the clinic by phone after performing each 
self-injection in order to confirm the date on which the injection was performed and report 
any AEs, including unplanned pregnancy, concomitant medications and injection site 
reactions.  During this phone call, the clinic staff will also record whether the subject had any
difficulties in performing the injection or had problems operating the device and what those 
issues were. In case the subject reports any injection site reactions, clinic staff will collect 
detailed information about the reaction (eg, timing; persistence; appearance; is it getting 
worse or better; how large or deep is it; how bothersome, etc.). All AEs, including 
unplanned pregnancy and injection site reactions will be recorded on AE CRF page.  Reasons 
for self-injection failure will also be recorded in the CRF.
If a participant fails to contact the clinic to report the injection date, the study centre
personnel shall not contact the patient until after the treatment window (+/- 1 week) for that 
planned injection has expired.  If at least 1 week has passed from the scheduled self-injection 
date and the clinic has not heard from the subject, the clinic staff will contact the subject to 
obtain the necessary follow-up information and provide appropriate instructions to the 
subject, depending on the circumstances.
If the subject fails to self-inject or report to clinic for an injection (supervised or administered 
by HCP) within the +/- 1 week treatment window, the subject should be advised to contact 
the clinic and speak to a healthcare professional regarding the need to exclude pregnancy 
before any additional injections, advice regarding additional contraception, and also for the 
timing of the next injection.  She should be advised to have a pregnancy test conducted prior 
to administering her next Sayana Press injection either at home or at the clinic.  The study 
centre must be informed if the subject has a positive at home pregnancy test and report to the 
clinic immediately.  An Exposure During Pregnancy Form must be completed and submitted 
to Pfizer within 24 hours of awareness.  The subject should also use a barrier method of 
contraception as instructed by the study investigator until she administers the next injection 
or, in cases when the subject decides to discontinue Sayana Press altogether, until the new 
contraceptive regimen is established.
Final Visit (Month 12 +/- 1 week) or Premature Discontinuation Visit
Subjects will return to the clinic for their final visit and the following procedures will be 
performed:
•
AE assessment;
•
Concomitant medications;
•
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 27
•
Physical examination;
•
Height and Weight;
•
Vital signs (sitting blood pressure and heart rate);
•
Urine pregnancy test;
•
Plasma sample for analysis of MPA (at select sites);
•
Drug accountability;
•
End of study form procedures (administrative).
 
 
 
 
 
 
 
 
6.4. Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures at a given study centre.
If a subject does withdraw they should return to the clinic to complete the Final Visit 
assessments.  If a subject does not return for a scheduled visit, every effort should be made to 
contact the subject.  All attempts to contact the subject and information received during 
contact attempts must be documented in the subject’s medical record).  In any circumstance, 
every effort should be made to document subject outcome, if possible.  The investigator 
should inquire about the reason for withdrawal, request that the subject return all unused
study drug, request that the subject return for a final visit, if applicable, and follow up with 
the subject regarding any unresolved AEs.
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 28
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator, which may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely fashion.
7.1. Pregnancy Testing
Urine pregnancy test, with sensitivity of at least 25 mIU/mL, will be performed at Screening, 
before Sayana Press administration at the Baseline Visit, and at the Final Visit.  A negative 
pregnancy result is required before the subject may receive the first Sayana Press injection.  
Pregnancy test will also be done in any instance when potential pregnancy is suspected, if the 
Sayana Press injection is not conducted per the required schedule and at the end of the study 
to confirm the subject has not become pregnant during the study.  Pregnancy tests may also 
be repeated as per request of institutional review boards (IRBs)/ethics committees (ECs) or if 
required by local regulations.  In the case of a positive confirmed pregnancy, the subject will 
be withdrawn from administration of the Sayana Press product and from the study.
If the subject fails to self-inject or report to clinic for an injection (supervised or administered 
by HCP) within the +/- 1 week treatment window, the subject should be advised to contact 
the clinic and speak to a healthcare professional regarding the need to exclude pregnancy 
before any additional injections, advice regarding additional contraception, and also for the 
timing of the next injection.  She should be advised to have a pregnancy test conducted at 
home or at the clinic prior to administering her next Sayana Press injection.  The study centre 
must be informed if the subject has a positive at home pregnancy test and report to the clinic 
immediately.  An Exposure During Pregnancy Form must be completed and submitted to 
Pfizer within 24 hours of awareness.  The subject should also use a barrier method of 
contraception as instructed by the study investigator until she administers the next injection 
or, in cases when the subject decides to discontinue Sayana Press altogether, until the new 
contraceptive regimen is established.
7.2. Assessments Questionnaires
 
 
 
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 29
 
 
7.3. Safety Assessments
Vital Signs
Vital signs including heart rate, sitting systolic and diastolic blood pressure will be taken at 
Screening, Baseline and Final Visits.
Weight and Height
Weight and height measurements will be conducted at Baseline and Final Visit.
General Physical Examination
General physical examination, including general appearance, vascular, nervous system, 
cardiovascular system and gastrointestinal system will be conducted at Screening and at the 
Final Visit.
Adverse Events Assessment
AE assessment will be performed at Screening, Baseline and Final Visits.  During the “at 
home” portion of the study, study subjects will contact the clinic by phone after performing 
each self-injection to report any AEs, including unplanned pregnancy and injection site 
reactions.  In case the subject reports any injection site reactions, the clinic staff will collect 
detailed information about the reaction (eg, timing; persistence; appearance, is it getting 
worse or better; how large or deep is it; how bothersome, etc.). The physical examination at 
the end of study will allow evaluation of the injection sites, and investigators should 
determine any sequelae at the injection sites that may be due to a persistent injection site 
reaction and report them as AEs or serious adverse events (SAEs) accordingly.
 
 
CCI
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 30
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 31
 
 
8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as an SAE
requiring immediate notification to Pfizer or its designated representative.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE.  The investigator is required to assess causality.  Follow-up by the investigator may be 
required until the event or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the subject provides informed consent, which is obtained prior to the subject’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product.  SAEs occurring to a subject after the active 
reporting period has ended should be reported to the sponsor if the investigator becomes 
aware of them; at a minimum, all SAEs that the investigator believes have at least a 
reasonable possibility of being related to investigational product are to be reported to the 
sponsor.
AEs (serious and non-serious) should be recorded on the case report form (CRF) from the 
time the subject has taken at least 1 dose of investigational product through the last subject
visit.
CCI
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 32
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to: 

Abnormal test findings;

Clinically significant symptoms and signs;
Unplanned pregnancy; Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong subject, at the wrong time, or at the wrong dosage strength.  
Such medication errors occurring to a study participant are to be captured on the Adverse 
Event page of the case report forms (CRFs), and on the SAE form when appropriate.  In the 
event of medication dosing error, the sponsor should be notified immediately.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 33
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error and, if applicable, any associated AE(s) are captured on an 
AE CRF page (refer to the Adverse Event Reporting Section for further details).
8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention;
and/or

Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.6. Serious Adverse Events
A Serious Adverse Event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalisation or prolongation of existing hospitalisation;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 34

Lack of efficacy in an approved indication should be reported as an SAE.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalisation.  The important medical event should be reported as serious, 
if it is determined that the event may jeopardize the subject or may require intervention to 
prevent one of the other AE outcomes.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalisation; 
or development of drug dependency or drug abuse.
Medical device complaints may meet the SAE reporting requirement criteria (see the section 
on Medical Device Complaint Reporting Requirements).  An incident is any malfunction (ie,
the failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a subject, or user, or of 
other persons, or to a serious deterioration in their state of health. 
A serious injury that can cause a serious deterioration in state of health can include:

A life-threatening illness, even if temporary in nature;

A permanent impairment of a body function or permanent damage to a body 
structure;

A condition necessitating medical or surgical intervention to prevent the above 
2 bulleted items;
Examples: clinically relevant increase in the duration of a surgical procedure; a 
condition that requires hospitalisation or significant prolongation of existing 
hospitalisation;

Any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.6.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in previous sections, and will be handled as SAEs in the safety 
database (see the section on Serious Adverse Event Reporting Requirements).


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 35
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to perform LFTs because of
clinical sign/symptom presenting in a subject, such LFT results should be handled and 
followed up as described below. 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s law cases) and should always be considered 
important medical events. 
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions.  Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (× ULN) concurrent with a total bilirubin value 2 × ULN with no evidence 
of hemolysis and an alkaline phosphatase value 2 × ULN or not available;

For subjects with preexisting ALT OR AST OR total bilirubin values above the 
ULN, the following threshold values should be used in the definition mentioned 
above:

For subjects with preexisting AST or ALT baseline values above the normal 
range: AST or ALT values 2 times the baseline values and 3 × ULN, or 
8 × ULN (whichever is smaller).
Concurrent with

For subjects with preexisting values of total bilirubin above the normal range: 
Total bilirubin level increased by 1 × ULN or ≥3 × ULN (whichever is smaller).
The subject should return to the investigational centre and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl 
transferase, prothrombin time (PT)/international normalized ratio (INR), and alkaline 
phosphatase.  A detailed history, including relevant information, such as review of ethanol, 
acetaminophen, recreational drug, and supplement consumption, family history, occupational 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 36
exposure, sexual history, travel history, history of contact with a jaundiced person, surgery, 
blood transfusion, history of liver or allergic disease, and work exposure, should be collected.  
Further testing for acute hepatitis A, B, or C infection and liver imaging (eg, biliary tract) 
may be warranted.  All cases confirmed on repeat testing as meeting the laboratory criteria 
defined above, with no other cause for LFT abnormalities identified at the time, should be 
considered potential Hy’s law cases irrespective of availability of all the results of the 
investigations performed to determine etiology of the abnormal LFTs.  Such potential Hy’s 
law cases should be reported as SAEs.
8.7. Hospitalisation
Hospitalisation is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation to an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalisation; 
however, the event leading to the emergency room visit should be assessed for medical 
importance.
Hospitalisation does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalisation or prolongation of hospitalisation in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 37

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalisation for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject;
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE.
8.8. Severity Assessment
If required on the AE CRFs, the investigator will use the adjectives MILD, MODERATE, 
or SEVERE to describe the maximum intensity of the AE.  For purposes of consistency, 
these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.9. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements if 
applicable.  An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the investigational product caused or contributed to an 
AE; generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor (see the section on Reporting Requirements).  If the 
investigator's causality assessment is "unknown but not related to investigational product," 
this should be clearly documented on study records. 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 38
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
8.10. Exposure During Pregnancy
For investigational products and for marketed products, an exposure during pregnancy occurs 
if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).
2. A male subject has been exposed (eg, because of treatment or environmental
exposure) to the investigational product prior to or around the time of conception 
and/or is exposed during his partner’s pregnancy.
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on an SAE report form and an EDP supplemental 
form, regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
subject reports that she is pregnant and has been exposed to a cytotoxic product by inhalation 
or spillage) using the EDP supplemental form.  This must be done irrespective of whether an 
AE has occurred and within 24 hours of awareness of the exposure. The information 
submitted should include the anticipated date of delivery (see below for information related 
to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up 
to the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 39
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the EDP may be requested by the investigator.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the study subject with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.11. Withdrawal Due to Adverse Events (See Also the Section on Subject Withdrawal)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page.
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.12. Eliciting Adverse Event Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject.  In addition, each study subject will be questioned about AEs.
8.13. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
8.13.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 40
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information.  This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of EDPand exposure via breastfeeding.
In the rare event that the investigator does not become aware of the occurrence of an SAE
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided.  In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.13.2. Non-serious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.
8.13.3. Medical Device Complaint Reporting Requirements
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be collected on the applicable pages within the CRF.  This 
includes potential incidents or malfunctions associated with the use of a medical device 
product.  An incident or malfunction is an event that might have led to death or serious 
deterioration in health, or if it occurred again might have led to death or serious deterioration 
in health.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event.
8.13.4. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 41
9. DATA ANALYSIS/STATISTICAL METHODS
9.1. Sample Size Determination
The primary endpoint for this study is the proportion of all attempted home self-injections 
that were successfully performed by the study participant at home and on schedule.  This will 
be presented as mean percentage of self- injections that were successfully administered, 
along with a 95% confidence interval using a clustered binomial analysis approach.  The 
self-administration success rate in a 1-year IIR study (GA678152) using data from 
56 subjects who each had up to 3 injections, was estimated to be 88.8%, with 95% 
confidence interval 83.1% to 92.7%.  This was determined using the generalized estimating 
equation (GEE) model for clustered binomial data, and estimated the intra-class correlation 
(ICC) to be 0.043.
Using a GEE model for clustered binomial data, and assuming the ICC to be 0.05, then for 
100 subjects, the half-width of the 95% confidence interval for different success rates is 
simulated to be the following:
Response rate
Half-width of 95% 
confidence interval
85%
4.6%
90%
3.8%
95%
2.8%
To allow for subjects who have never used Sayana previously, some subjects who may not be 
proficient at self-injection after the training and to allow for some subjects who may 
discontinue the study due to being lost to follow up, approximately 160 subjects will be 
enrolled to provide a sample size of at least 100 women who will perform the required 
self-injections at home and complete the follow-up questionnaires.
9.2. Statistical Methods
As this is a single arm study, there will be no treatment comparisons, and all analyses will be 
descriptive. 
9.2.1. Analysis of Primary Endpoint
The primary endpoint is the mean percent of home self-injections that were successfully 
administered.  Each subject will have a maximum of 3 home self-injections, each of which 
will be defined as a success or failure.  A success is defined as a home self-injection that was 
successfully performed by the study participant at home and on schedule (13 week interval 
+/- 1 week).  If the subject attempts but is unable to administer the self-injection at home and 
had it performed instead at the clinic, then that attempted self-injection would be classified as 
a failure.  If a subject discontinues from the study prior to attempting all 3 home 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 42
self-injections, or chooses not to attempt an injection at home, but has it performed in the 
clinic, then only the injections that were attempted at home will be evaluated and included in 
the analysis; ie, all attempts are included in the denominator.
For each subject we will calculate:
Proportion of attempted self-injections successfully administered at home= (# of successful 
home self-injections) / (total # of home self-injection attempts)
These binary outcomes are correlated within the subject, and they will therefore be analyzed
with a GEE model for clustered binomial data, using subject as the clustering variable.  The 
GEE model for this single-group analysis will use the logit link and will contain an intercept 
term; the 95% confidence interval for the intercept will be transformed to a 95% confidence 
interval for the self-injection success rate.
9.2.2. Analysis of Secondary Endpoint
The secondary endpoint is the continuation rate for the method at 1 year.  This is similar to 
the primary endpoint in study GA67815.2
The number and percentage of subjects completing 0 months (receiving only first injection), 
3 months (receiving first and second injections), 6 months (receiving first, second and third
injections), and 9 months (receiving all 4 injections but not returning for follow-up visit) will 
be determined.  Subjects had completed 12 months if they received all 4 injections, had a 
follow-up visit and were not recorded as discontinuing during the 12 month period.
The continuation rate equals:
•
(# subjects who have not discontinued by 12 months) / (total #  of subjects in study)
The total proportion of subjects who have not discontinued by 12 months (the follow-up 
visit) will be estimated along with a 95% confidence interval (CI), calculated using the 
normal approximation to the binomial.
 
 
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 43
 
 
 
 
 
 
 
 
 
 
9.2.5. Safety Analysis
Safety data, consisting of all adverse events, including unplanned pregnancies, persistent 
injection site reactions, SAEs, premature discontinuations, concomitant medications, vital 
signs, height and weight, and laboratory parameters, will be tabulated and listed according to 
Pfizer’s standard reporting algorithms. 
C
C
I
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 44
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to ensure 
that the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.
The study centre may be subject to review by the institutional review board (IRB)/ethics 
committee (EC), and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the subject’s chart in the hospitas or the physician's 
office.  In these cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents. 
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 45
consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to the International Conference of Harmonisation 
(ICH), according to local regulations, or as specified in the clinical study agreement (CSA), 
whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg,
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 1996 & 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 46
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by a numerical code consisting 
of a numbering system provided by Pfizer in order to de-identify study subjects. The study 
centre will maintain a confidential list of subjects who participated in the study, linking their
numerical code to the subject’s actual identity.  In case of data transfer, Pfizer will maintain 
high standards of confidentiality and protection of subjects’ personal data consistent with 
applicable privacy laws.
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consent documents used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB/EC before use, and available for inspection.
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed. The investigator 
will retain the original of each subject's signed consent document.
12.4. Subject Recruitment
Study centres will recruit study subjects from their clinic who they determine appropriate for 
study entry.  Additionally, advertisements and posters may be used as recruitment 
procedures.  Pfizer will provide study centres a template advertisement and template poster, 
if they choose to use them, and must be reviewed and approved by the local Ethics 
Committee prior to utilization.  Additional sites may be included if needed.
Pfizer will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used. 
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 47
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union (EU) is defined as the time at which it 
is deemed that a sufficient number of subjects have been recruited and completed the study 
as stated in the regulatory application (ie, clinical trial application [CTA]) and ethics 
application in the Member State.  Poor recruitment (recruiting less than the anticipated 
number in the CTA) by a Member State is not a reason for premature termination but is 
considered a normal conclusion to the study in that Member State.
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or study drug safety problems, or at the discretion of 
Pfizer. 
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) within 15 days.  As directed by Pfizer, all study 
materials must be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), www.pfizer.com, and/or the 
European Clinical Trials Database (EudraCT), and other public registries in accordance with 
applicable local laws/regulations. 
www.clinicaltrials.gov
Pfizer posts clinical trial Basic Results on www.clinicaltrials.gov for all Pfizer-sponsored 
interventional studies that evaluate the safety and/or efficacy of a Pfizer product.
15.2. Publications by Investigators
Pfizer has no objection to publication by investigator of any information collected or 
generated by investigator, whether or not the results are favorable to the investigational drug.  
However, to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure before it is submitted or otherwise disclosed.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 48
The investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to Pfizer 
at least 30 days before they are submitted for publication or otherwise disclosed.  If any 
patent action is required to protect intellectual property rights, the investigator agrees to delay 
the disclosure for a period not to exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information (other than the Study results themselves) before disclosure.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all centers.  However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the study at all 
participating sites, investigator is free to publish separately, subject to the other requirements 
of this section.
For all publications relating to the study, institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the Clinical Study Agreement between 
Pfizer and the institution.  In this section entitled Publications by Investigators, the defined 
terms shall have the meanings given to them in the Clinical Study Agreement.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 49
16. REFERENCES
1.
Prabhakaran S and Sweet A. Self-administration of subcutaneous depot 
medroxyprogesterone acetate for contraception: feasibility and acceptability. 
Contraception 2012; 85:453-457.
2.
Cameron ST, Glasier A and Johnstone A. Pilot study of home self-administration of 
subcutaneous depot-medroxyprogesterone acetate for contraception. Contraception
2012; 85:458-464.
3.
Beasley A and Westoff C. Self- versus clinical administration of depot 
medroxyprogesterone acetate (DMPA): A randomized clinical trial. Contraception 
2012; 86: 315.
4.
Williams R, Hensel D and Fortenberry JD. Self-administration of subcutaneous 
depot-medroxyprogesterone acetate by adolescent women.  Journal of Adolescent 
Health Abstracts 2010; 46:S17-S81.
5.
Beasley A, White KO, Cremers S, Westhoff C. Randomised clinical trial of self-versus 
clinical administration of subcutaneous depot medroxyprogesterone acetate. 
Contraception 2014; 89:352-6.
6.
UK Medical Eligibility Criteria (UKMEC 2009) www.fsrh.org


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 50
Appendix 1. Abbreviations 
This is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
CI
confidence interval
CRF
case report form
CSA
clinical study agreement
CTA
clinical trial application
DMPA
depot medroxyprogesterone acetate
EC
ethics committee
EDP
exposure during pregnancy
EU
European Union
EudraCT
European Clinical Trials Database
GCP
Good Clinical Practice
GEE
generalized estimating equation
HCP
health care professional
ICC
intra-class correlation
ICD
informed consent document
ICH
International Conference on Harmonisation
IFU
instructions for use
IND
Investigational New Drug
INR
international normalised ratio
IM
intramuscular
IRB
institutional review board
IUD
intrauterine device
LARC
long-acting reversible contraception
LFT
liver function test
MHRA
Medicines and Healthcare products Regulatory Agency
MPA
medroxyprogesterone acetate
MRP
Mutual Recognition Procedure
N/A
not applicable
PATH
Program for Appropriate Technology in Health
PMC
Post Marketing Commitment
PD
premature discontinuation
PK
Pharmacokinetic
PT
prothrombin time
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SOP
standard operating procedure


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 51
Abbreviation
Term
SmPC
summary of product characteristics
SRSD
single reference safety document
ULN
upper limit of normal
UK
United Kingdom
US
United States


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 52
Appendix 2. Instructions for Use.  Preparing and giving an injection with Sayana Press
Sayana Press is a disposable injector that contains a single dose of medicine sealed in a 
reservoir.  These instructions show step-by-step how to prepare and give the injection.
Step 1: Getting ready
You will need:
– A Sayana Press injector (in its sealed foil pouch).
– A suitable container for the used injector.
– A clean cotton pad or clean paper tissue.
Wash and dry your hands thoroughly before starting.
Check that the pouch does not appear to be damaged.
Check that the expiry date has not passed.
Ensure the pouch is at room temperature.
Step 2:  Selecting an injection area

Choose a suitable area for the injection, either the 
abdomen or the front upper thigh.  Avoid bony areas and 
the navel (belly button).

The area of skin must be free from scars and skin 
conditions such as eczema or psoriasis.

Change the site with each injection

Clean the area of skin as your healthcare provider has 
told you.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 53
Step 3:  Preparing the injector

Carefully tear open the foil pouch at the tear notch.

Take out the injector.  Do not remove the needle shield 
from the injector yet. 

Check the injector.  There should be a gap between the 
needle shield and the port.

Discard the injector and use a new one if :
–
There is no gap.
–
The injector is damaged.
The needle shield has come off or is missing.
Step 4:  Mixing the medicine

Hold the injector firmly by the port. 

Shake the injector vigorously for at least 30 seconds to 
mix the medicine.

The medicine should appear white and uniform.  If it is 
not, discard the injector and use a new one. 

If you see liquid leaking out or any other problem, 
discard the injector and use a new one. 

If there is a delay before injecting, you must repeat the 
mixing step.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 54
Step 5:  Activating the injector

Hold the injector firmly by the port, making sure the 
needle shield is pointing upwards.  Take care not to 
squeeze the reservoir. 

Hold the needle shield with the other hand.  

Push the needle shield firmly towards the port until it 
will go no further.  The injector is now activated.

Pull the needle shield off, and discard it in the sharps 
disposal container


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 55
Step 6: Injecting the dose

Gently pinch a large area of skin.  Keep the skin
pinched all through this step.

Hold the injector by the port with the needle
pointing straight downwards.

Insert the needle into the skin so that the port just
touches the skin.

Squeeze the reservoir slowly to inject the medicine.  
You should take about 5-7 seconds to do this.

Gently pull the needle out of the skin. Let go of the
skin.

Check whether any medicine has leaked out of the
injector or has appeared on the skin.

Do not replace the needle shield.

Use a clean cotton pad to press lightly on the injection
area for a few seconds. Do not rub the area.
Important advice

After the injection a small amount of medicine will
be left around the inside edge of the reservoir. This
is normal.

However, if any medicine has leaked out of the
injector or appeared on the skin, then a problem may
have occurred.

If you believe for any reason that the full dose has not 
been given, speak to your healthcare provider about 
alternative methods of contraception until the next 
scheduled injection.

Do not inject an additional dose.
After injection care:

If you get any symptoms of allergic reaction (see
leaflet Section 4 above) seek medical help
immediately.
Monitor the appearance of the injection site until the next
injection. If you notice any skin indentation or dimpling at
the injection site, tell your healthcare provider.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 56
Step 7: Disposing of the injector

Immediately dispose of the used injector into a suitable 
container in accordance with your local authority 
requirements or as you have been told by your 
healthcare provider.

The injector is for a single injection only and must not 
be re-used.
Step 8

Record the date of your injection and should you wish 
to continue, calculate the date of your next scheduled 
injection of Sayana Press
Retain this leaflet for your records.


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 57
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 58
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 59
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 60
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 61
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 62
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 63
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 64
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 65
CCI


Sayana Press (PN-008839) 
A6791040
Final Protocol, 26 January 2017
Page 66
CCI

SAP_000.pdf: 
Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 1
Protocol A6791040
PHASE IV OPEN LABEL SINGLE GROUP ONE YEAR STUDY OF HOME 
SELF-INJECTION WITH SAYANA® PRESS IN ADULT WOMEN OF 
REPRODUCTIVE AGE- A PRAGMATIC CLINICAL TRIAL
Statistical Analysis Plan 
(SAP)
Version:
1.1 (Amendment)
Author:
, Clinical Statistics, 
, 
Date:
31-AUG2018
PPD
PPD
PP
D


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 2
TABLE OF CONTENTS 
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................4
2. INTRODUCTION .................................................................................................................4
2.1. Study Objectives .......................................................................................................5
2.2. Study Design .............................................................................................................5
2.3. Sample Size...............................................................................................................6
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ..................................................................................................................6
3.1. Primary Endpoint(s) ..................................................................................................6
3.2. Secondary Endpoint(s) ..............................................................................................6
3.4. Baseline Variables.....................................................................................................7
3.5. Safety Endpoints .......................................................................................................7
4. ANALYSIS SETS .................................................................................................................8
4.1. Full Analysis Set .......................................................................................................8
4.2. Per Protocol Analysis Set..........................................................................................8
4.3. Safety Analysis Set....................................................................................................8
4.4. Other Analysis Sets ...................................................................................................8
5. GENERAL METHODOLOGY AND CONVENTIONS......................................................8
5.1. Hypotheses and Decision Rules ................................................................................8
5.2. General Methods .......................................................................................................8
5.2.1. Analyses for Binary Correlated Data............................................................8
5.2.2. Analyses for Binary Data..............................................................................9
5.2.3. Analyses for Categorical Data......................................................................9
5.3. Methods to Manage Missing Data ............................................................................9
6. ANALYSES AND SUMMARIES ........................................................................................9
6.1. Analysis of Primary Endpoint...................................................................................9
6.2. Analysis of Secondary Endpoint(s).........................................................................10
6.4. Correlation Analyses...............................................................................................11
CCI
CCI


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 3
6.5. Subset Analyses.......................................................................................................11
6.6. Baseline and Other Summaries and Analyses.........................................................11
6.6.1. Baseline Summaries....................................................................................11
6.6.2. Study Conduct and Subject Disposition .....................................................12
6.7. Safety Summaries and Analyses .............................................................................12
6.7.1. Adverse Events...........................................................................................12
6.7.2. Vital Signs ..................................................................................................13
6.7.3. Physical Examination .................................................................................13
7. INTERIM ANALYSES.......................................................................................................13
8. REFERENCES ....................................................................................................................14
9. APPENDICES .....................................................................................................................15


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 4
1. AMENDMENTS FROM PREVIOUS VERSION(S)
Amendment 
Number
Date
Section 
Changed
Summary of Changes
1
31August2018
6.1 
Analysis of 
Primary 
Endpoint 

Added plans for a sensitivity analysis.  A 
sensitivity analysis will be conducted for 
the primary endpoint; this analysis will 
exclude primary endpoint data for sites 
that required closure during the study due 
to Good Practice violations. 

Clarified definition of repeated attempts in 
a single visit. 
31August2018
6.3 
Analysis of 
Other 
Endpoint

Clarified that, endpoints will be 
summarized by visit and by who 
administered injection at clinic.
31August2018
6.7.1. 
Adverse 
Events 

Clarify language regarding analysis, AEs 
will be summarized by injection method.
30August2018
Appendix 2

Removal of Visit windows. 
2. INTRODUCTION
Study A6791040 is a Phase IV Open Label Single Group one year Study of Home 
Self-Injection with Sayana® Press in adult women of reproductive age, to be run in the 
United Kingdom.
This study is intended to provide information on the use of Sayana Press by women who 
self-inject the product at home over a 1-year period as part of Post Marketing Commitment 
(PMC) required by MHRA.
The application for approval of self-injection with Sayana Press was primarily based on a 
1-year investigator-initiated study (Study GA67815) that used Sayana (DMPA-SC in a 
pre-filled syringe) and a usability study that used Sayana Press (DMPA-SC in Uniject™) in 
which participants (volunteers) performed simulated injections into an injection trainer and 
assessed the functionality or usability of the device and the instructions for use for the device.  
While the GA67815 study showed that women can perform independent (at home) 
self-injection when using the pre-filled syringe, the Uniject™ device is fundamentally 
different from the syringe and MHRA has identified a need for a post-approval study that 
shows that women can similarly self- inject successfully when using the Uniject™ device 
rather than a standard pre-filled syringe.


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 5
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study A6791040.  This document may modify the plans outlined in the protocol; 
however, any major modifications of the primary endpoint definition or its analysis will also 
be reflected in a protocol amendment.
2.1. Study Objectives
Primary Objective:
•
Determine the proportion of women who are able to self-inject Sayana Press 
successfully over a 1-year period.
Secondary Objective:
•
Assess continuation rate for the method at 1 year.
 
 
 
2.2. Study Design
This is an open-label, single-arm, non-randomized, 1-year study to assess home 
self-administration of Sayana Press in women who desire long-acting reversible 
contraception (LARC), are interested to attempt DMPA self-injection at home and are judged 
by their HCP to be good candidates for self-injection. 
Following training and a supervised initial self-injection at the clinic, study participants will 
self-inject Sayana Press in the home setting every 3 months (at Month 3, Month 6 and 
Month 9) and return for a final study visit at Month 12.  Participants will attend 2 or 3 study 
visits at the clinic: a Screening/Baseline Visit or Screening and Baseline visit separately and 
a Final Visit.  At Months 3, 6 and 9, participants will be asked to contact the clinic by phone 
after performing each scheduled home self-injection in order to confirm the date of injection 
and to report any AEs, and/or injection difficulties or problems with the device. 
At the Month 12 Final Visit or premature discontinuation, subjects will be asked to complete 
the 
and the HCP will also complete a 
. 
CCI
CCI
CCI


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 6
2.3. Sample Size
The primary endpoint for this study is the proportion of all attempted home self-injections 
that were successfully performed by the study participant at home and on schedule. This will 
be presented as mean percentage of self- injections that were successfully administered,
along with a 95% confidence interval using a clustered binomial analysis approach. 
The self-administration success rate in a 1-year IIR study (GA678151) using data from
56 subjects who each had up to 3 injections, was estimated to be 88.8%, with 95% 
confidence interval 83.1% to 92.7%.  This was determined using the generalized estimating 
equation (GEE) model for clustered binomial data, and estimated the intra-class correlation 
(ICC) to be 0.043.
Using a GEE model for clustered binomial data, and assuming the ICC to be 0.05, then for 
100 subjects, the half-width of the 95% confidence interval for different success rates is 
simulated to be the following:
Response rate
Half-width of 
95% confidence 
interval
85%
4.6%
90%
3.8%
95%
2.8%
To allow for subjects who have never used Sayana previously, some subjects who may not be 
proficient at self-injection after the training and to allow for some subjects who may 
discontinue the study, approximately 160 subjects will be enrolled to provide a sample size 
of at least 100 women who will perform the required self-injections at home and complete 
the follow-up questionnaires.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
The primary endpoint will be the proportion of all attempted home self-injections that were 
successfully performed by the study participant at home (ie, not in the clinic under direct 
HCP supervision) and on schedule (13 week interval ±1 week). 
3.2. Secondary Endpoint(s)
•
Continuation rate for method at 1 year.
CCI


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 7
 
 
 
 
 
3.4. Baseline Variables
No baseline covariates in the planned analysis.
3.5. Safety Endpoints
Adverse events (AEs), including unplanned pregnancy and persistent injection site reactions, 
premature discontinuations, concomitant medications, vital signs and laboratory parameter 
(urine pregnancy test).
C
C
I


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 8
4. ANALYSIS SETS
Data for all subjects will be assessed to determine if subjects meet the criteria for inclusion in 
each analysis population prior to unblinding and releasing the database and classifications 
will be documented per standard operating procedures.
4.1. Full Analysis Set
The Full Analysis Set (FAS) will be defined as subjects who enroll into the study.  All 
summaries of efficacy parameters will be reported within the FAS population.
4.2. Per Protocol Analysis Set 
No per protocol analysis set is planned for this study.
4.3. Safety Analysis Set
The safety population will be defined exactly the same as the FAS population above.  The 
safety population will be used for all safety summaries.
4.4. Other Analysis Sets
No other analysis sets are planned for this study.
5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
As this is a single arm study, there will be no treatment comparisons, and all analyses will be 
descriptive.
5.2. General Methods 
5.2.1. Analyses for Binary Correlated Data
The primary endpoint is the mean percent of self-injections that were successfully 
administered (ie, combined across visits).  Each subject will have a maximum of 3 
self-injections, each of which will be defined as a success or failure. 
A success is defined as a home self-injection that was successfully performed by the study 
participant at home and on schedule (13 week interval 1 week).  If the subject attempts but 
is unable to administer the self-injection at home and had it performed instead at the clinic, 
then these are classed as failures.  If a subject discontinues from the study prior to attempting 
all 3 injections, or chooses not to attempt the injection at home, but have it performed in the 
clinic, then only the injections that were attempted at home will be evaluated and included in 
the analysis.
These binary outcomes are correlated within the subject, and they will therefore be analyzed 
with a generalized estimating equation (GEE) model for clustered binomial data, using 
subject as the clustering variable, to provide a proportion along with 95% confidence 
interval.


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 9
5.2.2. Analyses for Binary Data
For dichotomous categorical variable (continuation rate and proportion of attempted home 
self- injections where subject returned to clinic for the injection), the number of subjects and 
proportion will be presented, as well as a 95% confidence interval (using normal 
approximation to binomial).
5.2.3. Analyses for Categorical Data
For categorical variables (such as Subject and HCP questions), the counts and percent of 
subjects responding to each category will be presented. 
5.3. Methods to Manage Missing Data
Subjects with missing value for a given efficacy variable will not contribute to the analysis of 
that variable. 
6. ANALYSES AND SUMMARIES
All efficacy summaries and analyses will be conducted within the FAS population. Analyses 
will be primarily descriptive in nature.  No interim analyses are planned. 
6.1. Analysis of Primary Endpoint
The primary endpoint is the mean percent of home self-injections that were successfully 
administered (ie, combined across visits).  Each subject will have a maximum of 3 home 
self-injections, each of which will be defined as a success or failure.  A success is defined as 
a home self-injection that was successfully performed by the study participant at home and 
on schedule (13 week interval 1 week).  If the subject attempts but is unable to administer 
the self-injection at home and had it performed instead at the clinic, then that attempted 
self-injection would be classified as a failure.  If a subject discontinues from the study prior 
to attempting all 3 home self-injections, or chooses not to attempt an injection at home, but 
has it performed in the clinic, then only the injections that were attempted at home will be 
evaluated and included in the analysis; ie, all attempts are included in the denominator.  
When several home attempts occurred at a visit, the last attempt is counted at a visit.
These binary outcomes are correlated within the subject, and they will therefore be analyzed 
with a GEE model for clustered binomial data, using subject as the clustering variable. The 
GEE model for this single-group analysis will use the logit link and working correlation 
structure of independence. This GEE model will include only the intercept term and is used 
to obtain a 95% CI based on standard error estimates that take into account the correlation of 
binary observations within the patient; the point estimate and 95% CI for the intercept will be 
back-transformed (anti-logit transformation) to obtain the point estimate and 95% CI on the 
proportion scale.  The proportion estimate and 95% CI will be subsequently multiplied by 
100 to obtain results on the percent scale.  Note that proportion estimate from the GEE model 
equals: 
Proportion of attempted self-injections successfully administered at home= (total # of 
successful home self-injections) / (total # of home self-injection attempts).


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 10
A sensitivity analysis will be conducted for the primary endpoint; this analysis will exclude 
primary endpoint data for sites who required closure during study due to Good Clinical 
Practice violations.
6.2. Analysis of Secondary Endpoint(s)
The secondary endpoint is the continuation rate for the method at 1 year. This is similar to 
the primary endpoint in study GA67815.1
The number and percentage of subjects completing 0 months (receiving first injection), 
3 months (receiving first and second injections), 6 months (receiving first, second and third 
injections), and 9 months (receiving all 4 injections but not returning for follow-up visit) will 
be summarized.  Subjects had completed 12 months if they received all 4 injections, had a 
follow-up visit and were not recorded as discontinuing during the 12 month period.
The continuation rate equals:
(# subjects who have not discontinued by 12 months) / (total # of subjects in study).
The total proportion of subjects who have not discontinued by 12 months (the follow-up
visit) will be estimated along with a 95% confidence interval (CI), calculated using the 
normal approximation to the binomial.
 
 
 
 
 
 
 
CCI
CCI


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 11
 
 
 
 
6.4. Correlation Analyses
To describe the degree of relationship between the subject educational level to the subject’s
rating of the usefulness of training materials (based on Question 1 and Question 2 of subjects 
questionnaire), an analysis of correlation will be performed between these two categorical 
variables, the chi-square test and the resulting p-value, as well as the Cramér's V (φc) will be 
reported as a measure of correlation between these two variables.
6.5. Subset Analyses 
No subset analysis are planned for this study.
6.6. Baseline and Other Summaries and Analyses
6.6.1. Baseline Summaries
All demographic, baseline characteristics and pre-treatment conditions will be summarized 
using the safety population. Descriptive statistics, including number of patients, mean, 
standard error, median, and range for continuous variables, and frequency and percent for 
categorical variables, will be provided for all demographic, baseline characteristics, and 
pre-treatment conditions. 
C
C
I
CCI
CCI


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 12
6.6.2. Study Conduct and Subject Disposition
The number and percentage of patients, enrolled and treated in the study will be presented, 
together with the number and percentage of patients who withdrew from the study or study 
medication prematurely. A breakdown of the corresponding reasons for premature withdraw 
from study or study medication will be provided. 
A tabulation of the number and percentage of patients included in each analysis population 
will be provided. Reasons for exclusion from analysis population will also be provided.
Details on the subject disposition will be provided in subject listings. 
6.7. Safety Summaries and Analyses
Safety data, consisting of all adverse events, including unplanned pregnancies, persistent 
injection site reactions, SAEs, premature discontinuations, concomitant medications, vital 
signs, height and weight, and laboratory parameters, will be tabulated and listed according to 
Pfizer’s standard reporting algorithms.
6.7.1. Adverse Events
AE assessment will be performed at Screening, Baseline and Final Visits.  During the “at 
home” portion of the study, study subjects will contact the clinic by phone after performing 
each self-injection to report any AEs, including unplanned pregnancy (lack of efficacy) and 
injection site reactions. 
In case the subject reports any injection site reactions, the clinic staff will collect detailed 
information about the reaction (eg, timing; persistence; appearance, is it getting worse or 
better; how large or deep is it; how bothersome, etc.).  The physical examination at the end of 
study will allow evaluation of the injection sites, and investigators should determine any 
sequelae at the injection sites that may be due to a persistent injection site reaction and report 
them as AEs or serious adverse events (SAEs) accordingly.
Adverse events will also be summarized by injection method (ie, Self-injection at home, 
Supervised self-injection at clinic by health care provider and Other injections (including the 
injection performed by a friend). 
An adverse event is considered treatment emergent relative to a given treatment if:

The event occurs for the first time during the effective duration of treatment and was 
not seen prior to the start of treatment (for example, during the baseline or run-in 
period), or

The event was seen prior to the start of treatment but increased in severity during 
treatment.
AE reporting timeframe for this study will be 14 weeks after the last injection, or until the 
end of study visit, whichever is the earliest.


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 13
6.7.2. Vital Signs
Vital signs will be summarized and described at each visit. Vital signs including heart rate, 
sitting systolic and diastolic blood pressure will be taken at Screening, Baseline and Final 
Visits.  Weight and height measurements will be conducted at Baseline and Final Visit.
6.7.3. Physical Examination
General physical examination, including general appearance, vascular, nervous system, 
cardiovascular system and gastrointestinal system will be conducted at Screening and at the 
Final Visit.
7. INTERIM ANALYSES
No interim analyses are planned in this study. The final analyses will be performed after 
database release.


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 14
8. REFERENCES 
1.
Cameron ST, Glasier A and Johnstone A. Pilot study of home self-administration of 
subcutaneous depot-medroxyprogesterone acetate for contraception. Contraception 
2012; 85:458-464.
2.
Generalized Linear Models, 2nd Edition (Chapman & Hall Monographs on Statistics 
and Applied Probability 37) by P. McCullagh (Author), John A. Nelder (Author).
3.
Lui, K.J., Mayer, J.A., and Eckhardt, J. (2000), Confidence Intervals for the Risk Ratio 
under Cluster Sampling based on the Beta-Binomial Model, Statistics in Medicine, 19, 
2933-2942.
4.
Liang, K.Y. and Zeger, S.L. (1986), Longitudinal Data Analysis using Generalized 
Linear Models, Biometrika, 78, 13-22.


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 15
9. APPENDICES 
Appendix 1. SUMMARY OF EFFICACY ANALYSES
Endpoint/Variable
Analysis 
Set
Statistical 
Method
Timepoint
Interpretation
the proportion of all attempted 
home self-injections that were 
successfully performed by the 
study participant at home
FAS
GEE model 
(PROC 
GENMOD)
EOT
Primary 
Endpoint
Continuation rate for method at 1 
year.
FAS
Proportion & CI
EOT
Secondary 
Endpoint
 
 
 
 
 
 
 
 
 
CCI


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 16
Appendix 2. DATA SET DESCRIPTIONS
 will not be collected in the CRF; this dataset will be provided by sites 
and then converted into SAS data set for analysis.
CCI


Protocol A6791040 (Sayana Press) Statistical Analysis Plan
Page 17
Appendix 3. STATISTICAL METHODOLOGY DETAILS 
Sample SAS code to fit the GEE model repeated measures specified in Section 6.1. will be 
presented in the programming plan.