Clinical trial NCT03243305
Conditions: Contraception
Sponsor: Evofem Inc.
Start date: 2017-07-24; Completion date: 2018-11-29
Enrollment: 1384 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a single-arm, open-label, Phase III study in approximately 100 sites in the United States (US) over seven cycles of use in women aged 18 to 35 years who are at risk of pregnancy.

Detailed description:
Through assessments including pelvic examination, laboratory procedures, and medical and gynecological history, subjects will be screened for eligibility in order to enroll approximately 1349 subjects into the study. After a screening period of up to 60 days, enrolled women will receive study drug. Each woman will participate in the study until after she has completed treatment during seven study cycles. Women who have individual cycles that do not meet the criteria for an evaluable cycle will not have those cycles replaced by subsequent cycles in order to provide a total of seven evaluable cycles.

Arms: arm 1: This is a single-arm, open-label, Phase III study of AMPHORA , a non-hormonal contraceptive, at approximately 100 sites in the United States (US) over seven cycles of use in women aged 18 to 35 years who are at risk of pregnancy.
Interventions: intervention 1: AMPHORA
Intervention descriptions: intervention 1: non-hormonal contraceptive vaginal gel

Protocol documents:
Prot_000.pdf: 
AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 1 of 65  
 
 
 
 
 
 
Title: 
AMPOWER 
 
A SINGLE-ARM, PHASE III, OPEN-LABEL, MULTICENTER, 
STUDY IN WOMEN AGED 18-35 YEARS OF THE 
CONTRACEPTIVE EFFICACY AND SAFETY OF AMPHORA® 
CONTRACEPTIVE VAGINAL GEL 
 
Protocol Number: 
AMP002 
 
IND Number: 
109300 
 
Clinical Phase: 
III 
 
Sponsor: 
Evofem, Inc. 
 
12400 High Bluff Dr., Suite 600 
 
San Diego, CA 92130 
 
USA 
 
Phone: +1 858 550 1900 
 
Fax: +1 844 828 2010 
 
Clinical Research 
PAREXEL International 
Organization: 
195 West Street 
 
Waltham, MA 02541 
 
USA 
 
 
Phone: +1 781 487 9900 
 
Fax: +1 781 487 0525 
 
 
 
Original Protocol: 
Version 1, 05 May 2017 
 
Amendments: 
Version 2, 08 June 2017 
 
Version 3, 28 June 2017 
 
Version 4, 01 Nov 2017 
 


AMPHORA00 
Evofem, Inc. 
Title: 
PROTOCOL SIGNATURE PAGE 
AM POWER 
Protocol: AMP002 
Version 4 
A SINGLE-ARM, PHASE III, OPEN-LABEL, MULTICENTER, 
STUDY IN WOMEN AGED 18 TO 35 YEARS OF THE 
CONTRACEPTIVE EFFICACY AND SAFETY OF AMPHORA® 
CONTRACEPTIVE VAGINAL GEL 
Protocol Number: 
AMP002, Version 4 
IND Number: 
109300 
Clinical Phase: 
III 
Sponsor/Designee Signature: 
el y Culwell, MD, MPH, FA 
Chief Medical Officer 
Evofen, Inc. 
CONFIDENTIAL AND PROPRIETARY 
Date 
Page 2 o 65


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 3 of 65  
 
SIGNATURE PAGE FOR THE INVESTIGATOR 
 
Title: 
AMPOWER 
A SINGLE-ARM, PHASE III, OPEN-LABEL, MULTICENTER, 
STUDY IN WOMEN AGED 18-35 YEARS OF THE 
CONTRACEPTIVE EFFICACY AND SAFETY OF AMPHORA® 
CONTRACEPTIVE VAGINAL GEL 
Protocol Number: 
AMP002 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this study will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US state and federal regulations, all other applicable 
local regulatory requirements, and ICH guidelines. 
Organization: 
 
 
 
 
 
 
 
Signed: 
 
Date: 
 
 
Investigator 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 4 of 65  
 
TABLE OF CONTENTS 
1 
INTRODUCTION ..................................................................................................................19 
2 
STUDY OBJECTIVES ..........................................................................................................19 
2.1 
Primary ...............................................................................................................................19 
2.2 
Secondary ...........................................................................................................................19 
2.3 
Exploratory ........................................................................................................................20 
3 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARD/INDEPENDENT 
ETHICS COMMITTEE, EVOFEM, INC., AND PAREXEL PERSONNEL .......................20 
3.1 
Investigators and Institutional Review Board ....................................................................20 
3.2 
Clinical Research Organization .........................................................................................20 
3.3 
Clinical Study Period .........................................................................................................20 
4 
STUDY DESIGN ...................................................................................................................21 
4.1 
Subject Selection ................................................................................................................21 
4.1.1 
Inclusion Criteria .........................................................................................................22 
4.1.2 
Exclusion Criteria ........................................................................................................22 
4.1.3 
Screen Failures .............................................................................................................24 
4.2 
Informed Consent Process .................................................................................................25 
4.3 
Screening and Enrollment Procedures ...............................................................................25 
4.4 
Study Drug Use ..................................................................................................................25 
4.5 
Study Drug Packaging and Storage ...................................................................................25 
4.6 
Drug Accountability...........................................................................................................26 
4.7 
Laboratory Procedures .......................................................................................................26 
5 
STUDY PROCEDURES ........................................................................................................28 
5.1 
Study Visits ........................................................................................................................28 
5.1.1 
Screening Visit (Visit 1) ..............................................................................................28 
5.1.2 
Enrollment Visit (Visit 2) ............................................................................................29 
5.1.3 
Visit 3 and Visit 4 ........................................................................................................31 
5.1.4 
Visit 5 (Treatment Exit) ...............................................................................................33 
5.1.5 
Contact Between Visits ................................................................................................34 
5.1.6 
Unscheduled Safety Visits ...........................................................................................34 
5.2 
Emergency Contraception ..................................................................................................35 
5.3 
Pre-Trial and Concomitant Medications ............................................................................35 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 5 of 65  
 
5.4 
Adverse Events ..................................................................................................................35 
5.4.1 
Collection of Adverse Events ......................................................................................35 
5.4.2 
Definitions....................................................................................................................35 
5.4.3 
Assessment of Adverse Events ....................................................................................36 
5.4.4 
Reporting Serious Adverse Events ..............................................................................40 
5.4.5 
Follow-Up of Adverse Events .....................................................................................41 
5.4.6 
Pregnancy .....................................................................................................................41 
5.5 
Questionnaires ....................................................................................................................41 
5.6 
Electronic Diary .................................................................................................................41 
6 
STUDY CONDUCT ...............................................................................................................41 
6.1 
Deviation from the Protocol ...............................................................................................41 
6.2 
Protocol Approval and Amendment ..................................................................................42 
6.3 
Confidentiality ...................................................................................................................42 
6.4 
Discontinuation of Subjects ...............................................................................................42 
6.5 
Premature Termination of the Study ..................................................................................44 
6.6 
Pregnancy Determination/Pregnancy Review Committee .................................................44 
7 
STUDY MONITORING AND DOCUMENTATION ..........................................................45 
7.1 
Clinical Monitoring, Quality Control, and Quality Assurance ..........................................45 
8 
DATA MANAGEMENT .......................................................................................................46 
8.1 
Database Management and Quality Control ......................................................................46 
8.2 
Case Report Forms and Source Documentation ................................................................46 
8.3 
Data Collection ..................................................................................................................46 
8.4 
Study Documentation.........................................................................................................47 
8.5 
Data Processing ..................................................................................................................47 
8.6 
Retention of Data ...............................................................................................................47 
9 
STATISTICAL AND ANALYTICAL METHODS ..............................................................47 
9.1 
Outcome Evaluations .........................................................................................................47 
9.2 
Sample Size ........................................................................................................................48 
9.3 
Analysis Populations ..........................................................................................................48 
9.4 
Disposition of Subjects ......................................................................................................49 
9.5 
Demographic and Pre-Treatment Characteristics ..............................................................49 
9.6 
Treatment Exposure ...........................................................................................................49 
9.7 
Pre-Trial and Concomitant Medications ............................................................................49 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 6 of 65  
 
9.8 
Analyses of Pregnancy Experience ....................................................................................50 
9.8.1 
Primary Efficacy Analysis ...........................................................................................50 
9.8.1.1 
Derivation of the Primary Variable ........................................................................50 
9.8.2 
Secondary Analysis ......................................................................................................51 
9.8.3 
Sensitivity Analyses .....................................................................................................51 
9.9 
Safety Parameters ...............................................................................................................52 
9.9.1 
Incidence of Adverse Events .......................................................................................52 
9.9.2 
Other Safety Assessments ............................................................................................52 
9.10 
Other Endpoints .................................................................................................................52 
9.10.1 
Subject Satisfaction ......................................................................................................52 
9.10.2 
Pregnancy Intendedness ...............................................................................................52 
9.11 
Protocol Deviations ............................................................................................................52 
9.12 
Computer Methods.............................................................................................................53 
10 REVISION HISTORY ...........................................................................................................53 
11 REFERENCES .......................................................................................................................54 
12 APPENDICES ........................................................................................................................55 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 7 of 65  
 
LIST OF TABLES 
Table 1: 
Schedule of Assessments ..................................................................................13 
Table 2: 
Location for Laboratory Procedures .................................................................26 
Table 3: 
Vulvar, Vaginal, or Cervical Individual Signs/Symptoms Grading Table .......39 
Table 4: 
Summary of Amendments.................................................................................53 
 
LIST OF FIGURES 
Figure 1: 
Study Visit Timing Based on Menstrual Cycle at Enrollment ..........................15 
 
LIST OF APPENDICES 
Appendix A: 
Investigator Obligations ....................................................................................55 
Appendix B: 
CBC with Differential and Clinical Chemistry .................................................56 
Appendix C: 
Subject Satisfaction with Study Drug ...............................................................57 
Appendix D: 
Subject Sexual Satisfaction ...............................................................................58 
Appendix E: 
Sexual Function Questionnaire .........................................................................59 
Appendix F: 
Female Sexual Function Index ..........................................................................60 
Appendix G: 
Pregnancy Intendedness ....................................................................................65 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 8 of 65  
 
PROTOCOL SYNOPSIS 
TITLE OF CLINICAL TRIAL: 
AMPOWER 
A SINGLE-ARM, PHASE III, OPEN-LABEL, MULTICENTER STUDY IN WOMEN 
AGED 18 TO 35 YEARS OF THE CONTRACEPTIVE EFFICACY AND SAFETY OF 
AMPHORA® CONTRACEPTIVE VAGINAL GEL 
STUDY PRODUCT(S): 
Eligible subjects will receive: 
• Amphora® non-hormonal contraceptive vaginal gel (Amphora) supplied in individually 
wrapped 5 g single dose, pre-filled vaginal applicators. Amphora is a dense, viscous, off 
white to tan gel of uniform consistency. Its active ingredients are L-lactic acid United 
States Pharmacopeia (USP), citric acid USP, and potassium bitartrate USP, with alginic 
acid and xanthan gum included as viscosity and bioadhesive controllers 
CLINICAL PHASE: Phase III 
CLINICAL TRIAL OBJECTIVES: 
Primary: 
• 
To evaluate the contraceptive efficacy of Amphora over seven cycles of use  
Secondary: 
• To evaluate the contraceptive efficacy of Amphora as measured by the Pearl Index 
• To evaluate the safety of Amphora over seven cycles of use  
• 
To assess pregnancy outcomes  
Exploratory: 
• To assess subject satisfaction (including sexual satisfaction) with Amphora over seven 
cycles of use  
• To assess pregnancy intendedness for subjects treated with Amphora over seven cycles 
of use 
• 
To assess dosing time deviations for study drug-associated pregnancies 
OUTCOME EVALUATIONS: 
Primary: 
• Seven-cycle cumulative pregnancy rate as calculated using the Kaplan-Meier (KM) 
method  
Secondary: 
• Efficacy measured by the Pearl Index  
• Adverse events (AEs) 
• 
Pregnancy outcomes 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 9 of 65  
 
Exploratory: 
• Subject satisfaction  
• Sexual satisfaction 
• Pregnancy intendedness 
• 
Dosing time deviations for study drug-associated pregnancies 
CLINICAL TRIAL DESIGN: 
This is a single-arm, open-label, Phase III study in approximately 100 sites in the United States 
(US) over seven cycles of use in women aged 18 to 35 years who are at risk of pregnancy.  
TREATMENT DURATION: 
After a screening period of up to 60 days, women will be enrolled and receive Amphora. Each 
woman will participate in the study until after she has completed treatment during seven 
on-study menstrual cycles. The cycle during which enrollment occurs is Cycle 0. If the time 
from enrollment to the subject’s next menstrual period is ≥21 days, the subject’s seven study 
cycles will be Cycles 0-6. If the time from enrollment to the subject’s next menstrual period is 
<21 days, the subject’s seven study cycles will be Cycles 1-7. The final visit to the clinical site 
will take place 14 to 30 days after the seventh study cycle, or after the end of treatment if the 
subject discontinues treatment prematurely. 
SAMPLE SIZE: 
A sample of approximately 1349 women will receive Amphora. 
STUDY POPULATION: 
Study Sites: 
The study will be conducted at approximately 100 clinical sites in the US. Subjects will be 
selected for the study according to the eligibility criteria detailed below. 
Inclusion Criteria: 
To enroll in the clinical study, potential subjects must:  
1. Be healthy women, who are sexually active, at risk of pregnancy, and desiring 
contraception. 
2. Be within the age range of 18 to 35 years old (inclusive) at enrollment. 
3. In the opinion of the Investigator, be at low risk for both human immunodeficiency virus 
(HIV) and sexually transmitted infections (STIs) based on review of high risk behaviors 
and exposures according to the Centers for Disease Control Sexually Transmitted Infections 
(STI) Guideline. 
4. At the time of enrollment, have a single male sex partner for ≥3 months. 
5. Have a negative urine pregnancy test at enrollment. 
6. Have normal, cyclic menses with a usual length of 21 to 35 days over the last two cycles or 
at least two consecutive spontaneous menses (21 to 35 days in length) since delivery, 
abortion, or after discontinuing hormonal contraception or hormonal therapy prior to the 
date of consent. In addition: 
a. If the subject recently discontinued breastfeeding, she must have demonstrated return to 
regular cycling and have had at least three consecutive, spontaneous menses 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 10 of 65  
 
post-lactation prior to the date of consent. 
b. If the subject received prior administration of injectable contraceptives (e.g., depot-
medroxyprogesterone acetate [DMPA], Depo-Provera), there must be at least 10 months 
since the last injection and the subject must have had at least two consecutive, 
spontaneous menses prior to the date of consent. 
c. If a contraceptive implant was recently removed, the subject must have had at least 
two consecutive, spontaneous menses prior to the date of consent. 
d. If an intrauterine device (IUD) was recently removed, the subject must have had at least 
one spontaneous menses following removal and prior to the date of consent. 
7. Be willing to engage in at least three acts of heterosexual vaginal intercourse per cycle. 
8. Be willing to use the study drug as the only method of contraception over the course of the 
study (with the exception of emergency contraception [EC] in the event a subject engages 
in vaginal intercourse but believes that the study drug was not used properly or she is at risk 
for pregnancy for any other reason). 
9. Be capable of using the study drug properly and agree to comply with all study directions 
and requirements, including retaining the wrappers and returning them to the clinical site at 
the next study visit. 
10. Be willing to keep a daily electronic diary (eDiary) to record coital information, study drug 
use information, use of concomitant medications including other vaginal products and other 
contraceptives, menses, and sign and symptom data for the subject or as reported to her by 
her partner. 
11. Agree not to participate in any other clinical studies during the course of the study.  
12. Be capable and willing to give written informed consent to participate in the study.  
Exclusion Criteria: 
To enroll in the clinical study, potential subjects must not:  
1. Have had three or more urinary tract infections (UTIs) in the past year from the date of 
consent. 
2. Have a UTI by urine culture, chlamydia, gonorrhea, or symptomatic yeast vaginitis or 
symptomatic bacterial vaginosis (BV) diagnosed by wet mount, or trichomoniasis, unless 
treated and proof of cure is documented within the screening period. 
3. Have used vaginal or systemic antibiotics or antifungals within 14 days prior to enrollment, 
with the exception of vaginal or systemic antibiotics or antifungals completed for the 
treatment of a UTI, BV, or yeast vaginitis diagnosed at screening within seven days of the 
Enrollment Visit. 
4. Have a history of any recurrent vaginal infections/disorders (either greater than or equal to 
four times in the past year or greater than or equal to three times in the previous six months 
from the date of consent). 
5. Be pregnant, have a suspected pregnancy, or desire to become pregnant during the course of 
the study. 
6. Have a history of diagnosed infertility or of conditions that may lead to infertility, without 
subsequent non-assisted reproductive technology intrauterine pregnancy. 
7. Have any maternal contraindications to pregnancy (medical condition) or chronic use of 
medications for which significant evidence of fetal risk exists. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 11 of 65  
 
8. Have known or screen test positive for HIV infection. 
9. Have three or more outbreaks of genital herpes simplex virus (HSV) within the last year 
from the date of consent or be receiving suppressive therapy. 
10. Have visible genital condylomata (warts). 
11. Be lactating or breastfeeding. 
12. Have any clinically significant abnormal finding on physical examination including pelvic 
examination or baseline laboratory assessments which, in the opinion of the Investigator, 
precludes study participation. 
13. Have clinically significant signs of vaginal or cervical irritation on pelvic examination. 
14. Be planning to have any (e.g., diagnostic or therapeutic) vaginal or cervical procedures 
during the period of the study. 
15. Have an abnormal Papanicolaou test (Pap test) based on the following criteria: 
a. Pap test in the past 12 months from the date of screening with atypical squamous 
cells of undetermined significance (ASC-US) unless at least one of the 
following criteria is met: 
i. Less than 21 years of age. 
ii. A repeat Pap test at least six months later was normal. 
iii. Reflex human papillomavirus (HPV) testing was performed and was 
negative for high-risk HPV. 
iv. A colposcopy (with or without biopsy) found no evidence of dysplasia 
requiring treatment or treatment was performed and follow up at least 
six months after the treatment showed no evidence of disease. 
b. Pap test in the past 12 months from the date of screening with low grade 
squamous intraepithelial lesion (LSIL) unless at least one of the following 
criteria is met: 
i. Less than 21 years of age. 
ii. A colposcopy (with or without biopsy) found no evidence of dysplasia 
requiring treatment or treatment was performed and follow up at least 
six months after the treatment showed no evidence of disease. 
c. Pap test in the past 12 months from the date of screening with atypical squamous 
cells in which high grade squamous intraepithelial lesion cannot be excluded 
(ASC-H), atypical glandular cells, high grade squamous intraepithelial lesion 
(HSIL), or ≥30 years old who are cytology-negative and HPV 16- or HPV 18-
positive unless colposcopy and/or treatment was performed and follow up at 
least six months after the colposcopy and/or treatment showed no evidence of 
disease. 
d. Pap test in the past 12 months with malignant cells. 
16. Consume (on average) more than three drinks of an alcoholic beverage per day. 
17. In the opinion of the Investigator, have a history of substance abuse in the last 12 months.  
18. Have taken an investigational drug or used an investigational device within the past 30 days 
from the date of consent. 
19. In the opinion of the Investigator, have issues or concerns that may compromise the safety 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY 
 
Page 12 of 65  
 
of the subject, impact the subject’s compliance with the protocol requirements, or confound 
the reliability of the data acquired. 
20. Be an Evofem, PAREXEL, or clinical site employee regardless of direct involvement in 
research activities, or their close relative. 
 


AMPHORA® 
 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 13 of 65 
Table 1: 
Schedule of Assessments 
 
Visit 1 
Visit 2 
Visit 3 
Telephone Visit 
Between Visits 3 and 4 
Visit 4 
Visit 5b 
Procedures 
Screening 
Day -60 to 0 
Enrollment 
Cycle 0 
(During 2nd 
Study Cycle)a 
(During Either 3rd or 4th 
Study Cycle) 
(During Either 5th 
or 6th Study Cycle) 
14-30 Days After 7th 
Study Cycle/ Exit Visit 
Written Informed Consent/HIPAA 
X 
 
 
 
 
 
Eligibility (Inclusion/Exclusion)  
X 
X 
 
 
 
 
Medical/Gynecological Historyc 
X 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Enrollment 
 
X 
 
 
 
 
Prior History of Contraceptive Use 
(Past Year) 
X 
X 
 
 
 
 
Pre-Trial Medications 
X 
X 
 
 
 
 
Vital Signsd  
X 
X 
X 
 
X 
X 
CBC with Differential and Chemistrye 
X 
 
 
 
 
X 
HIV Teste 
X 
 
 
 
 
 
Physical Examinationf 
X 
 
 
 
 
X 
Gynecological Examinationg 
X 
X 
X 
 
X 
X 
Pap Test 
Xh 
 
 
 
 
 
Chlamydia/Gonorrhea Test 
X 
 
Xi 
 
Xi 
Xi 
Urine Culturej 
X 
 
 
 
 
X 
Dipstick Urinalysisk 
Xl 
X 
X 
 
X 
Xl 
Urine Pregnancy Testm 
X 
X 
X 
 
X 
X 
Serum Pregnancy Test 
 
X 
 
 
 
X 
Distribute eDiaryn 
 
X 
 
 
 
 
Review eDiaryn 
 
 
X 
X 
X 
X 
Dispense/Return Study Product 
 
Xo 
X 
 
X 
X 
Subject Satisfaction with Study 
Product Questionnaire 
 
X 
X 
 
X 
X 
Sexual Satisfaction Questionnaire 
 
X 
X 
 
X 
X 
Pregnancy Intendedness Questionnaire 
 
X 
X 
 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
Concomitant Medications 
 
X 
X 
X 
X 
X 
Between-Visit Contactp 
 
 
 
X 
 
 
Schedule Next Visit/Contactq 
Xr 
X 
X 
X 
X 
 
Post-Study Treatment Contraceptions  
 
 
 
 
X 
X 


AMPHORA® 
 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 14 of 65 
Footnotes from Table 1 above 
Abbreviations: BV=bacterial vaginosis; CBC=complete blood count; eDiary=electronic diary; HIPAA=Health Insurance Portability and Accountability Act; HIV=human 
immunodeficiency virus; Pap test=Papanicolaou test; Tel=telephone contact; UTI=urinary tract infection. 
a. The time period between Visit 2 and Visit 3 will vary based subject’s first on-study cycle as defined in Figure 1. 
b. Treatment will end after seven study cycles. The cycle at enrollment will be included as one of the seven study cycles only if the time from enrollment to the start of the 
next menstrual period was ≥21 days. 
c. Includes documentation of the start date of last menstrual period. 
d. Height, weight, and blood pressure will be measured at Screening. Only weight and blood pressure will be measured at subsequent visits. 
e. Central laboratory will analyze CBC with differential, chemistry panels, and perform HIV test and chlamydia and gonorrhea assessments at Screening. Urine microscopy 
and culture and Pap tests will be performed locally. 
f. Physical examination to include assessment of heart, lungs, and abdomen, and a breast examination at the discretion of the Investigator.  
g. Gynecological examination is to include a speculum and bimanual examination. Investigators will note the presence or absence of vulvar, vaginal, or cervical findings, 
including epithelial disruption, or areas of obvious erythema; these will be assessed as either not present, mild, moderate, or severe; the presence or absence of bleeding, 
petechiae, or sloughing will also be recorded (Section 5.4.3). Clinically significant changes from Baseline as judged by the Investigator are to be reported as AEs. If a 
woman experiences any significant gynecological symptoms, she should return to the clinical site as soon as possible for a gynecological examination. Wet mount and 
vaginal pH for monilia, BV, and trichomonas will be performed only for symptomatic women.  
h. Results from a Pap test performed at the screening clinical site ≤12 months prior to the Screening Visit may be used provided the report is available. 
i. Chlamydia and gonorrhea assessments to be performed at Visits 3, 4, and 5 only if the subject indicates that she has changed sexual partners or is symptomatic. If the 
subject reports that her partner has been diagnosed or is being treated, she should be assessed/treated as per clinical site standard. 
j. In addition to the urine culture at Screening and Visit 5, subjects will be instructed to contact the clinical site to schedule a dipstick urinalysis and possibly a urine culture 
any time they suspect they may have a UTI. 
k. If dipstick urinalysis is 1+ for analytes of blood, leukocyte esterase, protein or nitrites, the urine should be sent for urine culture and microscopic urinalysis.  
l. Only to be performed if the subject presents to the clinical site with urinary symptoms. Dipstick urinalysis should be performed at any visit where a subject presents to the        
center with urinary symptoms.  
m. A urine pregnancy test should be administered any time a subject misses her period or suspects pregnancy. If a subject reports a positive home pregnancy test, a serum 
β-hCG should be performed.  
n. Subjects will record in their eDiary dates/times of gel use, dates/times of sexual activity, vaginal bleeding, and use of back-up contraception (including reasons for back-up 
contraception, if applicable). Additionally, subjects will record gel-related genitourinary side effects (vaginal itching, burning, or pain) and assess them as mild, moderate, 
or severe; these side effects and non-menstrual cycle vaginal spotting/bleeding will be analyzed as AEs. At each visit, Amphora and eDiary compliance data will be 
reviewed and subjects assessed for re-education. Between visits, sites and subjects will receive alerts if a subject has missed eDiary entries. Sites will record documentation 
of contact with the subject around eDiary compliance. 
o. Provide instructions on how to use the study drug at Enrollment Visit. 
p. Between-visit telephone contact is to include assessment of AEs, concomitant medications, sexual activity, use of backup contraception, compliance with use of the study 
drug and eDiary, need for an unscheduled visit, and confirmation of contact information. 
q. Includes confirmation of subject contact information. At the Enrollment Visit and each subsequent study visit/contact, the subject should be reminded to not have 
intercourse, use the study drug, or place anything in the vagina within 24 hours of the next scheduled visit to the clinical site. 
r. Perform Enrollment Visit upon verification that all eligibility criteria have been met. 
s. At Visit 4, the clinical site staff is to discuss post-treatment contraception with the subject, which would be started at completion of Cycle 7. 
t. The final visit to the clinical site will take place 14-30 days after the seventh study cycle or after the end of treatment if the subject discontinues treatment prematurely. 
 
 


AMPHORA® 
 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 15 of 65 
Figure 1: 
Study Visit Timing Based on Menstrual Cycle at Enrollment 
 
V=clinical site visit 
Visit 5/Exit visit is to take place 14-30 days after the seventh study cycle or from last use of study product for early termination (unless being followed for pregnancy) 
Telephone Visit is to take place between V3 and V4 
Notes: Duration of Cycle 0 is number of days from enrollment to start of first on-study menstrual period. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 16 of 65 
 
LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
ADL 
Activities of Daily Living 
AE 
Adverse event 
AMPOWER 
A Single-Arm, Phase III, Open-Label, Multicenter, Study in Women 
Aged 18 to 35 Years of the Contraceptive Efficacy and Safety of 
Amphora® Contraceptive Vaginal Gel 
ASC-H 
Atypical squamous cells, cannot exclude high grade squamous 
intraepithelial lesion 
ASC-US 
Atypical squamous cells of undetermined significance 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
β-hCG 
Beta-human chorionic gonadotropin 
BUN 
Blood urea nitrogen 
BV 
Bacterial vaginosis 
CBC diff 
Complete blood count differential 
CFR 
Code of Federal Regulations 
CFU 
Colony-forming units 
CI 
Confidence interval 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMPA 
Depot medroxyprogesterone acetate 
DRL 
Drug Reference List 
EC 
Emergency contraception 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
EE 
Efficacy-evaluable 
FDA 
Food and Drug Administration 
FSFI 
Female sexual function index 
GCP 
Good Clinical Practice 
hCG 
Human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act  


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 17 of 65 
 
Abbreviation 
Definition 
HIV 
Human immunodeficiency virus 
HPV 
Human papillomavirus 
HSIL 
High grade squamous intraepithelial lesion 
HSV 
Herpes simplex virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IUD 
Intrauterine device 
IWRS 
Interactive Web Response System 
KM 
Kaplan-Meier 
LB 
Lactobacillus 
LDH 
Lactate dehydrogenase 
LSIL 
Low grade squamous intraepithelial lesion 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
MITT 
Modified Intent-to-Treat 
N-9 
Nonoxynol-9 
NAAT 
Nucleic acid amplification testing 
NDA 
New Drug Application 
OTC 
Over-the-counter 
Pap test 
Papanicolaou test 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SOP 
Standard operating procedure 
STI 
Sexually transmitted infection 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 18 of 65 
 
Abbreviation 
Definition 
Tel 
Telephone/Telephone contact 
UMC 
Uppsala Monitoring Centre 
USP 
United States Pharmacopeia 
UTI 
Urinary tract infection 
WBC 
White blood cell 
WHO 
World Health Organization 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 19 of 65 
 
1 INTRODUCTION 
 
Unintended pregnancies are a significant concern throughout the world and are often associated 
with adverse maternal and child outcomes.1,2 Despite recent declines, unintended pregnancy 
remains a widespread problem, as an estimated 2.8 million unintended pregnancies occur 
annually in the US, representing 45% of all pregnancies. 
 
The 14% of women at risk who do not practice contraception at all, or who have gaps of a month 
or more during the year, account for 54% of all unintended pregnancies. According to research 
conducted by the Centers for Disease Control and Prevention (CDC), approximately 40% of 
women surveyed after unintended birth who were not using contraception at the time of 
conception noted one of the following three reasons for nonuse: did not expect to have sex, 
worried about side effects of birth control, or male partner didn’t want to use birth control 
(17.3%, 14.1%, and 8.0%, respectively).1 Therefore, for certain women, an ideal product might 
be one that takes effect immediately, lacks systemic side effects, and is female controlled. This 
would be consistent with research indicating a preference by some women for short-acting, on-
demand contraceptives that are easily reversible.3,4 
 
Amphora® contraceptive vaginal gel (Amphora) is a novel, non-hormonal, surfactant-free, 
contraceptive developed to have acidifying, bioadhesive, and viscosity-retaining properties to 
provide effective acidification of the male ejaculate in the vagina and to form a long-lasting layer 
of gel over the vaginal and cervical surfaces.5,6 As Amphora is non-hormonal, it may be a viable 
option for women who are reluctant to use hormonal contraceptives due to side effects or for 
whom hormonal contraceptives are contraindicated, which represents approximately 13%-16% 
of the population.7,8 Amphora is also intended to help fill a gap in the contraceptive landscape for 
women who prefer a rapidly reversible, non-daily and/or on-demand contraception, experience 
allergy or sensitivity to nonoxynol-9 (N-9), or do not want to rely on a partner’s collaboration. 
Compatibility studies indicate that Amphora can safely be used concomitantly with barrier 
methods,9,10,11 such as diaphragms and condoms, which provides reassurance considering 
evidence suggesting that some women prefer to use multiple types of contraceptives 
simultaneously.12 As there is no other method currently available that has all the unique 
characteristics of Amphora, it will expand the contraceptive options currently available to 
women. 
 
This Phase III study is designed to further confirm the safety and effectiveness of Amphora 
demonstrated in a previous Phase III study. 
2 STUDY OBJECTIVES 
2.1 
Primary 
• To evaluate the contraceptive efficacy of Amphora over seven cycles of use  
2.2 
Secondary 
• To evaluate the contraceptive efficacy of Amphora as measured by the Pearl Index 
• To evaluate the safety of Amphora over seven cycles of use  


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 20 of 65 
 
• 
To assess pregnancy outcomes  
2.3 
Exploratory 
• To assess subject satisfaction (including sexual satisfaction) with Amphora over seven 
cycles of use 
• To assess pregnancy intendedness for subjects treated with Amphora over seven cycles of 
use 
• 
To assess dosing time deviations for study drug-associated pregnancies  
3 INVESTIGATORS, INSTITUTIONAL REVIEW 
BOARD/INDEPENDENT ETHICS COMMITTEE, EVOFEM, INC., 
AND PAREXEL PERSONNEL 
3.1 
Investigators and Institutional Review Board 
The multicenter clinical study described in this protocol will be conducted in compliance with 
the 1996 revision of the Declaration of Helsinki,13 International Conference on Harmonisation 
(ICH) Consolidated Good Clinical Practice (GCP) (E6), and all applicable FDA regulations. This 
clinical study will be conducted under contracts administered by Evofem, Inc. (the Sponsor) with 
clinical monitoring, data handling, statistical analyses, and study report production performed by 
PAREXEL or designees. The study will be conducted at approximately 100 clinical sites in the 
US. A complete list of Investigators, Sub-Investigators, and Coordinators, and their affiliations 
will be maintained in the Trial Master File. A recognized Institutional Review Board (IRB) must 
consider and give approval and continuing review for all participating clinical sites.  
3.2 
Clinical Research Organization 
 
PAREXEL International 
195 West Street 
Waltham, MA 02541 
USA  
Phone: +1 781 487 9900 
Fax: +1 781 487 0525 
 
Adverse Event Reporting 
Refer to Section 5.4.4. 
3.3 
Clinical Study Period 
Each woman will participate until she has been treated for seven on-study menstrual cycles. The 
cycle in which enrollment occurs is Cycle 0 (Figure 1). If the time from enrollment to the 
subject’s next menstrual period is ≥21 days, the subject’s seven study cycles will be Cycles 0-6 
(Figure 1a). If the time from enrollment to the subject’s next menstrual period is <21 days, the 
subject’s seven study cycles will be Cycles 1-7 (Figure 1b). The final visit to the clinical site will 
take place 14 to 30 days after the seventh study cycle or after the end of treatment if the subject 
discontinues treatment prematurely. If a pregnancy is deemed to have occurred on-treatment and 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 21 of 65 
 
the subject discontinues or is lost to follow up, attempts will be made to follow such pregnancies 
(up to three attempts followed by a certified letter). AEs considered to be possibly related to 
study drug will be followed to resolution or, for chronic conditions, deemed stable, even if this 
occurs beyond the study period. The last electronic Case Report Form (eCRF) should be 
completed within two weeks of the final assessment. 
4 STUDY DESIGN 
The proposed study design is a single-arm, open-label, Phase III study in approximately 100 sites 
in the US over seven cycles of use in women aged 18 to 35 years who are at risk of pregnancy. 
The primary endpoint is the seven-cycle cumulative pregnancy rate as calculated using the KM 
method. Secondary endpoints proposed include efficacy as measured by the Pearl Index, AEs, 
and pregnancy outcomes. In addition, exploratory endpoints proposed include subject 
satisfaction, sexual satisfaction, pregnancy intendedness, and dosing time deviations for 
Amphora and associated pregnancies. Safety will be measured by reported AEs.  
Through assessments including pelvic examination, laboratory procedures, and medical and 
gynecological history, subjects will be screened for eligibility in order to enroll approximately 
1349 subjects into the study. After a screening period of up to 60 days, enrolled women will 
receive study drug. Each woman will participate in the study until after she has completed 
treatment during seven study cycles, as described in Section 3.3. Criteria to determine whether 
an individual cycle is evaluable for efficacy are described in Section 9.8. Women who have 
individual cycles that do not meet the criteria for an evaluable cycle will not have those cycles 
replaced by subsequent cycles in order to provide a total of seven evaluable cycles. 
Subjects will be expected to attend five visits: Screening (Visit 1), Enrollment (Visit 2), Visit 3 
(during the second study cycle), Visit 4 (during either the fifth or sixth study cycle), and Visit 5 
(14 to 30 days after seventh study cycle) as described in Section 5.1. In addition, subjects will be 
contacted by telephone by the clinical site staff between Visits 3 and 4 to monitor AEs, 
concomitant medications, sexual activity, use of backup contraception, compliance with use of 
the study drug and electronic diary (eDiary), need for an unscheduled visit, and confirmation of 
contact information. In the event that the subject reports any significant gynecological symptoms 
or any symptoms indicative of a possible UTI, she will be asked to contact the clinical site for 
possible evaluation. During further unscheduled safety visits, the Investigator may perform a 
gynecological exam and appropriate laboratory tests, and provide appropriate treatment as 
necessary.  
An independent expert Pregnancy Review Committee will review all confirmed pregnancies. 
The Pregnancy Review Committee will determine if the pregnancy occurred on treatment 
(defined as date of conception between enrollment and <8 days after final study drug use) or not 
on treatment (defined as date of conception prior to enrollment or ≥8 days following final study 
drug use), or whether there is insufficient information for adjudication. Subjects with an on-
treatment pregnancy will discontinue drug but remain in the study for follow-up.  
4.1 
Subject Selection 
Subjects will be treated and followed as outpatients. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 22 of 65 
 
4.1.1 
Inclusion Criteria 
To enroll in the clinical study, potential subjects must:  
1. Be healthy women, who are sexually active, at risk of pregnancy, and desiring contraception. 
2. Be within the age range of 18 to 35 years old (inclusive) at enrollment. 
3. In the opinion of the Investigator, be at low risk for both HIV and STIs based on review of 
high risk behaviors and exposures according to the Centers for Disease Control Sexually 
Transmitted Infections (STI) Guideline. 
4. At the time of enrollment, have a single male sex partner for ≥3 months.  
5. Have a negative urine pregnancy test at enrollment. 
6. Have a normal, cyclic menses with a usual length of 21 to 35 days over the last two cycles or 
at least two consecutive spontaneous menses (21 to 35 days in length) since delivery, 
abortion, or after discontinuing hormonal contraception or hormonal therapy prior to the date 
of consent. In addition: 
a. If the subject recently discontinued breastfeeding, she must have demonstrated return to 
regular cycling and have had at least three consecutive, spontaneous menses 
post-lactation prior to the date of consent. 
b. If the subject received prior administration of injectable contraceptives (e.g., depot-
medroxyprogesterone acetate [DMPA], Depo-Provera), there must be at least 10 months 
since the last injection and the subject must have had at least two consecutive, 
spontaneous menses prior to the date of consent. 
c. If a contraceptive implant was recently removed, the subject must have had at least 
two consecutive, spontaneous menses prior to the date of consent. 
d. If an intrauterine device (IUD) was recently removed, the subject must have had at least 
one spontaneous menstrual period following removal and prior to the date of consent. 
7. Be willing to engage in at least three acts of heterosexual vaginal intercourse per cycle. 
8. Be willing to use the study drug as the only method of contraception over the course of the 
study (with the exception of emergency contraception [EC] in the event a subject engages in 
vaginal intercourse but believes that the study drug was not used properly or she is at risk for 
pregnancy for any other reason). 
9. Be capable of using the study drug properly and agree to comply with all study directions and 
requirements, including retaining the wrappers and returning them to the clinical site at the 
next study visit. 
10. Be willing to keep a daily eDiary to record coital information, study drug use information, 
use of concomitant medications including other vaginal products and other contraceptives, 
menses, and sign and symptom data for the subject or as reported to her by her partner. 
11. Agree not to participate in any other clinical studies during the course of the study.  
12. Be capable and willing to give written informed consent to participate in the study 
4.1.2 
Exclusion Criteria 
To enroll in the clinical study, potential subjects must not:  
1. Have had three or more UTIs in the past year from the date of consent. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 23 of 65 
 
2. Have a UTI by urine culture, chlamydia, gonorrhea, or symptomatic yeast vaginitis or 
symptomatic BV diagnosed by wet mount, trichomoniasis, unless treated and proof of cure is 
documented within the screening period. 
3. Have used vaginal or systemic antibiotics or antifungals within 14 days prior to enrollment, 
with the exception of vaginal or systemic antibiotics or antifungals completed for the 
treatment of a UTI, BV, or yeast vaginitis diagnosed at screening within seven days of the 
Enrollment Visit. 
4. Have a history of any recurrent vaginal infections/disorders (either greater than or equal to 
four times in the past year or greater than or equal to three times in the previous six months 
from the date of consent). 
5. Be pregnant, have a suspected pregnancy, or desire to become pregnant during the course of 
the study. 
6. Have a history of diagnosed infertility or of conditions that may lead to infertility, without 
subsequent non-assisted reproductive technology intrauterine pregnancy. 
7. Have any maternal contraindications to pregnancy (medical condition) or chronic use of 
medications for which significant evidence of fetal risk exists. 
8. Have known or screen test-positive for HIV infection. 
9. Have three or more outbreaks of genital HSV within the last year from the date of consent or 
be receiving suppressive therapy. 
10. Have visible genital condylomata (warts). 
11. Be lactating or breastfeeding. 
12. Have any clinically significant abnormal finding on physical examination including pelvic 
examination or baseline laboratory assessments which in the opinion of the Investigator, 
precludes study participation. 
13. Have clinically significant signs of vaginal or cervical irritation on pelvic examination. 
14. Be planning to have any (e.g., diagnostic or therapeutic) vaginal or cervical procedures 
during the period of the study. 
15. Have an abnormal Pap test based on the following criteria: 
a. Pap test in the past 12 months from the date of screening with atypical squamous cells of 
undetermined significance (ASC-US) unless at least one of the following criteria is met: 
i. Less than 21 years of age. 
ii. A repeat Pap test at least six months later was normal. 
iii. Reflex HPV testing was performed and was negative for high-risk HPV. 
iv. A colposcopy (with or without biopsy) found no evidence of dysplasia requiring 
treatment, or treatment was performed and follow-up at least six months after the 
treatment showed no evidence of disease. 
b. Pap test in the past 12 months from the date of screening with low grade squamous 
intraepithelial lesion (LSIL) unless at least one of the following criteria is met: 
i. Less than 21 years of age. 
ii. A colposcopy (with or without biopsy) found no evidence of dysplasia requiring 
treatment, or treatment was performed and follow-up at least six months after the 
treatment showed no evidence of disease. 
c. Pap test in the past 12 months from the date of screening with atypical squamous cells in 
which high grade squamous intraepithelial lesion cannot be excluded (ASC-H), atypical 
glandular cells, high grade squamous intraepithelial lesion (HSIL), or ≥30 years old who 
are cytology-negative and HPV 16- or HPV 18-positive unless colposcopy and/or 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 24 of 65 
 
treatment was performed and follow-up at least six months after the colposcopy and/or 
treatment showed no evidence of disease. 
d. Pap test in the past 12 months with malignant cells. 
16. Consume (on average) more than three drinks of an alcoholic beverage per day. 
17. In the opinion of the Investigator, have a history of substance abuse in the last 12 months. 
18. Have taken an investigational drug or used an investigational device within the past 30 days 
from the date of consent. 
19. In the opinion of the Investigator, have issues or concerns that may compromise the safety of 
the subject, impact the subject’s compliance with the protocol requirements, or confound the 
reliability of the data acquired. 
20. Be an Evofem, PAREXEL, or clinical site employee regardless of direct involvement in 
research activities, or their close relative. 
4.1.3 
Screen Failures 
Subjects who completed the informed consent process but do not meet all eligibility criteria 
within the 60-day screening period will be screen failures. Screen failure subjects may be 
rescreened two additional times at the Investigator’s discretion, following approval by the 
Sponsor/PAREXEL. There must be a minimum of two weeks between each rescreening. Each 
time a subject is rescreened, a new informed consent form (ICF) must be signed. 
All screening procedures and laboratory tests (CBC, chemistry, urinalysis, urine culture, 
chlamydia, gonorrhea, urine pregnancy test) will be repeated upon rescreening. HIV test will not 
be repeated if the original test still falls within the 60-day screening window. The subject must 
meet all eligibility criteria prior to enrollment. 
The screen failure must be registered in the interactive web response system (IWRS). Upon 
rescreening, the subject will be assigned a new screening number in the IWRS. A link between 
the previous screening number and the new screening number will be created in the IWRS and 
the electronic data capture (EDC) system. 
If a blood sample must be redrawn (e.g., due to sample handling problems, breakage or sample 
integrity), this is not considered a rescreening. 
Further details regarding the procedure for rescreening may be found in the Site Reference 
Manual (SRM). 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 25 of 65 
 
4.2 
Informed Consent Process 
The principles of informed consent will be implemented according to the 1996 revision of the 
Declaration of Helsinki, ICH Consolidated GCP (E6), and applicable FDA regulations. 
It is the Investigator's responsibility to ensure that each subject is provided an explanation of the 
details contained in the Informed Consent Form (ICF) prior to the individual signing and dating 
the form certifying voluntary participation in the study. The Investigator will not undertake any 
eligibility testing for the study until valid consent has been obtained. If required by the IRB a 
witness (impartial observer to the informed consent process) must also sign and date the ICF. 
The signed and dated ICF must be retained by the Investigator as part of the study records. The 
subject is to also receive a copy of the ICF after signatures by the Investigator or his/her 
designees. 
4.3 
Screening and Enrollment Procedures 
Each subject who provides informed consent at the Screening Visit (Visit 1) will be assigned a 
screening number by the IWRS. The Investigator (or designee) must ensure that the subject is 
eligible to participate in the study before enrollment and the Coordinator must verify subject 
eligibility with the Investigator (or designee) prior to enrollment and/or dispensing study drug.  
Study drug will be labeled with a unique code.  
Further details can be found in the IWRS User Manual. 
4.4 
Study Drug Use 
Eligible subjects will receive study drug to use as their method of contraception while engaging 
in vaginal sexual intercourse. Study drug will be provided in a prefilled applicator containing 5-
grams of drug. 
Subjects will be instructed to administer a single pre-filled applicator of study drug 
intravaginally a maximum of one hour before each episode of vaginal intercourse. Additional 
applications of study drug should be administered before each additional act of vaginal 
intercourse regardless of the time of the last application (e.g., if vaginal intercourse occurs more 
than once in a day). If more than one hour passes before starting intercourse, an additional 
application of study gel must be applied. 
Subjects should be encouraged not to douche during the study; however, if douching does occur, 
the subject should wait at least six hours after the last act of intercourse and should record the 
product used as a concomitant medication in the eDiary. Similarly, subjects should be advised 
not to use lubricants or other vaginal preparations before or during intercourse. If use does occur, 
it should be recorded in the eDiary and as a concomitant medication. 
4.5 
Study Drug Packaging and Storage 
The study drug will be provided in pre-filled applicators. Each clinical site will receive a supply 
sufficient for the anticipated number of study participants.  


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 26 of 65 
 
Each subject will receive a supply of pre-filled applicators as well as detailed instructions for 
administering the study drug. While at the clinical site, study drug must be stored within the 
appropriate temperature range and secured in a limited-access area. Once distributed, subjects 
will be asked to store the study drug at room temperature and not to refrigerate or freeze it. The 
clinical site is not permitted to release supplies of the study drug for distribution by any person 
not named as an Investigator for the study or to provide these supplies to persons not enrolled in 
the study. 
4.6 
Drug Accountability 
Study drug will be shipped by PAREXEL or its designee to each clinical site after the receipt and 
acceptance of all necessary regulatory documents. The Investigator is responsible for 
maintaining accurate accountability records throughout the study. Each dispensing must be 
documented in the EDC system. At each study visit, the subject will be provided with a 
minimum of 1 carton of study drug containing 10 pre-filled applicators.  
Subjects should return all unused pre-filled applicators at each study visit; for used or partially 
used product, only the wrapper should be returned at each study visit. Return of these items will 
be recorded in the EDC system. The clinical site must account for and properly document all 
study drug returned by subjects during each visit. In order to receive additional shipments of 
study drug, a request from the clinical site must be emailed or faxed to their study monitor or the 
designated contact.  
The Investigator is responsible for returning all unused study drug to the Sponsor/PAREXEL for 
disposal. Alternatively, unused study drug may be disposed of by the clinical site staff at the 
discretion of the Sponsor/PAREXEL. The Investigator must verify that all unused drug supplies 
have been returned by the subject and that no remaining supplies are in the Investigator’s 
possession.  
4.7 
Laboratory Procedures 
Laboratory procedures will be performed as described in the Laboratory Manual at either the 
local laboratory or central laboratory. 
Table 2: 
Location for Laboratory Procedures   
Local Laboratory or Site 
Central Laboratory 
Dipstick urinalysis (study test kit to be 
provided) 
CBC differential 
Urine culture 
Clinical chemistry 
Urine pregnancy test (study test kit provided) 
Serum pregnancy test 
Pap test 
HIV  
Wet Mount Analysis 
Chlamydia 
Vaginal pH 
Gonorrhea 
Urine pregnancy test:  


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 27 of 65 
 
Clinical sites will be provided with urine pregnancy test kits, and urine pregnancy testing will be 
performed locally by the clinical site in accordance with the schedule of assessments.  
Urine dipstick and culture: 
Urine for urinalysis will be obtained as a clean-catch specimen. Dipstick urinalysis will be 
performed using study test kit provided. Urine culture will be performed locally by the clinical 
sites under usual procedures for such tests.  
A clinical diagnosis of a symptomatic UTI will be made at the clinical site using the following 
criteria:  
• complaint of urinary symptoms; 
•  1+ for analytes of blood, leukocyte esterase, protein or nitrites; and 
• a minimum bacterial count of 10,000 colony-forming units (CFU)/mL with the presence 
of uropathogen.  
A symptomatic UTI may also be diagnosed by the presence of symptoms and a 
≥100,000 CFU/mL presence of uropathogen without a positive leukocyte esterase by dipstick. A 
clinical diagnosis of an asymptomatic UTI will be made at the clinical site using the following 
criteria: absence of symptoms and a bacterial count of ≥100,000 CFU/mL with the presence of 
uropathogen. 
Pap tests:  
Pap tests will be analyzed locally at the laboratory chosen by the clinical site.  
Wet Mount Analysis (monilia, BV, trichomonas) and Vaginal pH: 
For symptomatic women only, wet mount analysis for the presence of monilia, BV, and 
trichomonas will be performed locally at the clinical site. Clinical diagnosis of BV will be made 
at the clinical site following Amsel’s criteria with at least three of the following four findings 
confirmed:  
• 
homogeneous, thin, white discharge that smoothly coats the vaginal walls; 
• 
clue cells ≥20% (e.g., vaginal epithelial cells studded with adherent coccobacilli) on 
microscopic examination; 
• 
pH of vaginal fluid >4.5; or 
• 
a fishy odor of vaginal discharge before or after addition of 10% KOH (i.e., the whiff 
test). 
Central Laboratory: 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 28 of 65 
 
Serum pregnancy tests: 
Beta-human chorionic gonadotropin (β-hCG) testing will be performed at a central laboratory on 
serum samples at the Enrollment Visit and Visit 5/Exit Visit. In addition, subjects who report a 
positive urine home pregnancy test or have a documented positive urine human chorionic 
gonadotropin (hCG) test performed at the site after enrollment should have a serum quantitative 
β-hCG test performed at the central laboratory, preferably on the same day as the urine 
pregnancy test. 
CBC differential (CBC diff), clinical chemistry: 
Blood samples will be collected in accordance with the schedule of assessments for CBC diff 
and clinical chemistry testing at a central laboratory. CBC diff and clinical chemistry laboratory 
assessments are provided in Appendix B. 
HIV, chlamydia, gonorrhea: 
Blood samples for HIV testing will be collected in accordance with the schedule of assessments. 
Assessments for the diagnosis of chlamydia and gonorrhea will be performed by a central 
laboratory using a urine sample (not clean-catch) or vaginal swab. 
5 STUDY PROCEDURES 
5.1 
Study Visits 
5.1.1 
Screening Visit (Visit 1) 
Women who present to the clinical site for gynecologic care will be asked to participate in the 
study. Informed consent must be obtained prior to any study-specific procedures being 
performed. Please refer to Table 1 for a schedule of study assessments to be performed. The 
Screening Visit procedures do not have to be completed on a single day if more time is necessary 
(e.g., if a subject has a condition that requires treatment, as described below, or is menstruating). 
The following events will occur at the Screening Visit: 
• 
Obtain signed and dated informed consent and give a copy to potential subject 
• 
Review inclusion/exclusion criteria 
• 
Collect demographic information (age, race, ethnicity) 
• 
Collect medical, gynecological, and pregnancy history. Gynecological history will 
include the start date of last menstrual period  
• 
Vital signs (height, weight, and blood pressure) 
• 
Record pre-trial medications (inquire about subject self-medication for suspected UTIs, 
including any herbal or natural supplements), present use and 6-month history 
• 
Record history of contraceptive use in the past year 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 29 of 65 
 
• 
Physical exam including assessment of heart, lungs, and abdomen, and a breast exam at 
the discretion of the Investigator 
• 
Gynecological exam including assessment of the vulva, vaginal wall, cervix, adnexae, 
and uterus by speculum and bimanual exam. Wet mount and vaginal pH for monilia, BV, 
and trichomonas will be performed only for symptomatic women. 
• 
Pap test (unless results performed ≤ 12 months prior to the Screening Visit are obtained) 
• 
Vaginal swab or urine sample taken for chlamydia and gonorrhea tests 
• 
Blood sample collection for CBC diff, clinical chemistry, and HIV test 
• 
Urine pregnancy test 
• 
Dipstick urinalysis (only to be performed if the subject presents to the center with urinary 
symptoms) 
• 
Urine culture 
• 
Review partner risk of HIV and STIs (according to CDC guidelines) to the best of the 
potential subject’s knowledge 
• 
Confirm subject contact information 
• 
The Enrollment Visit will be performed upon confirmation that all eligibility criteria have 
been met 
If the subject presents at the Screening Visit and is diagnosed with chlamydia or gonorrhea, and 
all other eligibility criteria are met, she will be treated and allowed to enter the study after proof 
of cure is documented and it is at least 21 days since treatment. Test of cure is recommended 
3-4 weeks after completing treatment for chlamydia or gonorrhea.14 
If the subject presents at the Screening Visit and is diagnosed with a UTI, symptomatic BV, or 
symptomatic yeast vaginitis, and all other eligibility criteria are met, she will be prescribed 
appropriate treatment and allowed to enter the study after proof of cure is documented and it is at 
least seven days since treatment. Test of cure is recommended seven days after completing 
treatment for a UTI. Dipstick urinalysis will be repeated at the Enrollment Visit, which should be 
scheduled for seven or more days after the subject completes the treatment prescribed for the 
UTI. 
5.1.2 
Enrollment Visit (Visit 2) 
If the subject meets all eligibility criteria, she will be scheduled for an Enrollment Visit within 
60 days of the date of consent. If Screening Visit procedures are performed over more than one 
day, the Enrollment Visit will be scheduled within 60 days of the first the date of consent. Proof 
of cure must be documented for subjects diagnosed at the Screening Visit with UTI, 
symptomatic BV, trichomoniasis, symptomatic yeast vaginitis, chlamydia, or gonorrhea. 
At the Enrollment Visit, the following will occur: 
• 
Verify that all eligibility criteria have been met 
• 
Review medical and gynecological history; update start date of last menstrual period 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 30 of 65 
 
• 
Update pre-trial medications and record concomitant medications (inquire about subject 
self-medication for suspected UTIs, including any herbal or natural supplements)  
• 
Update history of contraceptive use within the past year 
• 
Vital signs (weight and blood pressure only) 
• 
Urine pregnancy test 
• 
Serum quantitative β-hCG pregnancy test 
• 
Dipstick urinalysis (if 1+ or greater for any analyte of blood, leukocyte esterase, protein, 
or nitrite results are positive, the urine should be sent for urine culture and microscopic 
urinalysis. 
• If the Enrollment Visit dipstick urinalysis is negative, the subject can be enrolled.   
• If the Enrollment Visit dipstick urinalysis test is positive, the subject may not be 
enrolled in the study at this visit and a urine culture will be performed.  
o If the urine culture is positive, the subject will be a screen failure and can be 
rescreened. If a UTI is diagnosed, the subject cannot be enrolled until proof 
of cure is documented. 
o If the urine culture is negative, the subject may return and be enrolled in the 
study. 
• 
Perform gynecological exam, including assessment of the vulva, vaginal wall, cervix, 
adnexae, and uterus (bimanual and speculum). Wet mount and vaginal pH for monilia, 
BV, and trichomonas will be performed only for symptomatic women.  
• 
Administer questionnaires to assess subject satisfaction with most recent birth control 
method, sexual satisfaction, and pregnancy intendedness 
• 
Dispense study drug to subject (enough to last until next scheduled visit) 
• 
Provide instructions on how to use the study drug  
• 
Dispense eDiary and provide instructions on how to use it 
• 
Record AEs 
• 
Provide emergency contact information to study participant 
• 
Remind subjects of their right to use EC during the study 
• 
Encourage subjects not to have intercourse, use the study drug, or place anything in the 
vagina within 24 hours of the next scheduled clinical site visit 
• 
Schedule the next study visit 
• 
Confirm subject contact information 
• 
Update medical history 
Subjects will be instructed to contact the clinical site as soon as possible if any of the following 
occur: 
• 
She is about to run out of study drug. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 31 of 65 
 
• 
Her period is late by one week or more or she suspects she might be pregnant for any 
reason. 
• 
She suspects she might have a UTI, vaginal infection, BV or sexually transmitted 
infection or has sought care at another facility for a UTI, vaginal infection or vaginosis 
including BV, or sexually transmitted infection. 
• 
She experiences any medical problem, whether or not she thinks it is related to the study 
drug. 
• 
She has any questions about using the study product or about the study. 
• 
She wishes to stop using the study drug as her method of contraception or to discontinue 
from the study. 
• 
She misses or expects to miss a scheduled visit. 
• 
She experiences any technical difficulty with the eDiary. See Section 5.6 for eDiary 
instructions.  
5.1.3 
Visit 3 and Visit 4 
Subjects will return to the clinical site for Visit 3 (during the second study cycle) and for Visit 4 
(during either the fifth or sixth study cycle). The following events will occur during these interim 
visits: 
• 
Vital signs (weight and blood pressure only) 
• 
Gynecological exam including assessment of the vulva, vaginal wall, cervix, adnexae, 
and uterus (bimanual and speculum); wet mount and vaginal pH for monilia, BV, and 
trichomonas will be performed only for symptomatic women 
• 
Urine pregnancy test (if positive, serum sample is collected to be sent to central 
laboratory for a serum quantitative β-hCG test [Section 4.7]), bimanual exam for uterine 
sizing, and transvaginal ultrasound, preferably on the same day 
• 
Dipstick urinalysis (if analytes are 1+ positive or greater for blood, leukocyte esterase, or 
protein, or nitrite results are positive, the urine will be sent for urine culture and 
microscopic analysis) 
• 
Perform chlamydia and gonorrhea tests only if the subject indicates that she has changed 
sexual partners or is symptomatic. If, according to the subject, her partner has been 
diagnosed or is being treated, she should be assessed per clinical site standard.  
• 
Administer questionnaires to assess subject satisfaction with study drug, sexual 
satisfaction, and pregnancy intendedness 
• 
Review eDiary data report for completeness and accuracy, and assess the need for subject 
re-training in eDiary use 
• 
Review study drug adherence data 
• 
Review backup contraception use and sexual activity 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 32 of 65 
 
• 
Collect unused study drug and unused applicators, and record study drug accountability 
information 
• 
Re-supply study drug, as necessary 
• 
Record concomitant medications (including any herbal or natural supplements) 
• 
Record AEs 
• 
Remind subjects of their right to use EC during the study 
• 
Encourage subjects not to have intercourse, use the study drug, or place anything in the 
vagina within 24 hours of the next scheduled clinical site visit 
• 
Visit 4 only: discuss post-study contraception with the subject to be started after 
completion of cycle 7 and before Visit 5/Exit Visit  
• 
Schedule the next clinical site visit 
• 
Confirm subject contact information 
If the subject presents to an interim visit and is diagnosed with a UTI, symptomatic BV, 
trichomoniasis or symptomatic yeast vaginitis, she will be treated and allowed to continue in the 
study. All diagnosed or suspected conditions will be noted in the EDC system. 
Based on gynecologic exam at each visit, investigators will note the presence or absence of 
vulvar, vaginal, or cervical findings (as defined in Section 5.4.3), including epithelial disruption, 
or areas of obvious erythema; these will be assessed as either not present, mild, moderate, or 
severe; the presence or absence of bleeding, petechiae, or sloughing will also be recorded on the 
gynecological exam eCRF. These findings will be reported as an AE if considered by the 
Investigator to be a clinically significant change from baseline, defined as an at least one level 
increase in severity of the finding from baseline. 
If, during the eDiary review, the clinical site detects any pattern of incorrect or inconsistent drug 
usage, the subject will again be provided with proper usage instructions for the study drug. In 
addition, the eDiary data report will be reviewed to ensure that it does not contain reports of any 
signs or symptoms related to drug use. If a sign or symptom is reported in the subject eDiary that 
warrants follow-up, the subject may be contacted for further information as necessary and may 
be asked to return to the clinical site for evaluation and/or treatment.  
At each interim visit, all subjects will be reminded to contact the clinical site as soon as possible 
if any of the following occur: 
• 
She is about to run out of study drug. 
• 
Her period is late by one week or more or she suspects she might be pregnant for any 
reason. 
• 
She suspects she might have a UTI or has sought care at another facility for a UTI, 
vaginal infection, or vaginosis, including BV, or sexually transmitted infection. 
• 
She experiences any medical problem, whether or not related to the study drug. 
• 
She has any questions about using the study drug or about the study. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 33 of 65 
 
• 
She wishes to stop using the study drug as her method of contraception or to discontinue 
from the study. 
• 
She misses or expects to miss a scheduled visit. 
• 
She experiences any technical difficulty with the eDiary.  
• 
The clinical site should contact the subject within one business day if a notification is 
received that the subject has missed an eDiary entry. 
5.1.4 
Visit 5 (Treatment Exit) 
Subjects will return to the clinical site 14-30 days after the seventh study cycle for exit from the 
study (Visit 5; Treatment Exit Visit). The following study activities will occur at this visit. In 
addition, these procedures should also be performed any time a subject discontinues the study 
prematurely. 
• 
Vital signs (weight and blood pressure only) 
• 
Perform physical examination (heart, lungs, and abdomen, and a breast exam at the 
discretion of the Investigator) 
• 
Gynecological examination, including assessment of the vulva, vaginal wall, cervix, 
adnexae, and uterus. Wet mount for monilia, BV, and trichomonas will be performed 
only for symptomatic women. 
• 
Perform chlamydia and gonorrhea tests only if the subject indicates that she has changed 
sexual partners or is symptomatic. If, according to the subject, her partner has been 
diagnosed or is being treated, she should be assessed per clinical site standard. 
• 
CBC diff and chemistry panels to be sent to central laboratory for analysis 
• 
Urine pregnancy test (if the test is positive and the pregnancy is deemed to be on-
treatment, the subject should not be discontinued from the study but should have 
pregnancy assessments) 
• 
Serum quantitative β-hCG pregnancy test 
• 
Dipstick urinalysis (only to be performed if the subject presents to the center with urinary 
symptoms) 
• 
Urine culture 
• 
Administer questionnaires to assess subject satisfaction with study drug, sexual 
satisfaction, and pregnancy intendedness 
• 
Review eDiary data report for completeness and accuracy 
• 
Review study drug use adherence data 
• 
Review backup contraception use and sexual activity 
• 
Collect unused study drug and wrappers, and record drug accountability information 
• 
Record concomitant medications (including any herbal or natural supplements) 
• 
Record AEs 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 34 of 65 
 
• 
Discuss post-study contraception with the subject  
• 
For subjects who are discontinuing early from the study, the clinical site personnel should 
provide counseling about alternative methods of birth control and referral, as applicable 
Investigators will note the presence or absence of vulvar, vaginal, or cervical findings (as defined 
in Section 5.4.3), including epithelial disruption, or areas of obvious erythema; these will be 
assessed as either not present, mild, moderate, or severe; the presence or absence of bleeding, 
petechiae, or sloughing will also be recorded on the gynecological exam eCRF and reported as 
an AE if considered by the Investigator to be a clinically significant change from baseline, 
defined as an at least one level increase in severity of the finding from baseline. 
eDiary data reports will be reviewed to ensure that they do not contain any reported signs or 
symptoms related to drug use. If a sign or symptom is reported in the subject diary that warrants 
follow-up, the subject may be contacted for further information as necessary and may be asked to 
return to the clinical site for evaluation and/or treatment.  
5.1.5 
Contact Between Visits 
Subjects will be contacted by telephone by the clinical site staff between Visits 3 and 4. All such 
contacts and attempts should be documented in the subject's source file. Between-visit contact is 
to include the following assessments: 
• 
Record AEs 
• 
Record concomitant medications (including any herbal or natural supplements) 
• 
Review eDiary data reports for completeness and accuracy, and assess the need for 
subject re-training in eDiary use 
• 
Review study drug adherence data 
• 
Review backup contraception use and sexual activity 
• 
Confirm subject has sufficient supply of study drug 
• 
Identify any other issues; plan an unscheduled visit, if necessary 
• 
Confirm subject contact information 
5.1.6 
Unscheduled Safety Visits 
In the event that the subject reports any significant gynecological symptoms or any symptoms 
indicative of a possible UTI, she will be asked to contact the clinical site for evaluation. During 
unscheduled safety visits, the Investigator may perform a gynecological exam and appropriate 
laboratory tests and provide appropriate treatment as necessary. Subjects should be discouraged 
from any self-medication with vaginal products; rather, they should visit the clinical site for 
assessment and treatment. Similarly, subjects should be discouraged, but not prohibited, from 
seeking treatment for suspected UTIs or other vaginal infections at facilities other than the 
clinical site. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 35 of 65 
 
Based on the results of the gynecological exam and laboratory tests, if the Investigator 
determines that the subject should be discontinued, the Treatment Exit procedures (as detailed in 
Section 5.1.4) will be performed and the subject will be discontinued from the study. In addition, 
if at any time during the study a subject misses her period or suspects that she may be pregnant, 
she should call the clinical site to schedule a urine pregnancy test. 
5.2 
Emergency Contraception 
In the event a subject engages in vaginal intercourse but believes that the study drug was not 
used properly or if she feels she is at risk for pregnancy for any other reason, she is eligible to 
request a prescription for EC or obtain her own as OTC. The individual clinical sites will provide 
EC in accordance with the standard of care of the clinical site. Any time EC use occurs, the date 
of usage as well as the reason for usage should be recorded as a concomitant medication in the 
source and the EDC system as well as the eDiary. 
5.3 
Pre-Trial and Concomitant Medications 
At the Screening Visit and Enrollment Visit, the study subjects will be asked to report 
medications and health products that were taken at the time of screening and prior to enrollment, 
including any herbal or natural supplements, over the past six months. The subject’s 
contraceptive use within the past year will also be recorded at these study visits.  
The use of concomitant medications and health products will also be queried in the eDiary, at 
Visits 2-5 and during the between-visit contact. If vaginal symptoms are present, the subject 
should visit the clinical site for evaluation and treatment as indicated. Subjects should be 
instructed to abstain from any vaginal self-medication. All medications and health products taken 
by the participant during the course of the study, including all vaginal preparations and any 
medication given for the treatment of any AE must be recorded in the EDC system. 
Subjects should be encouraged not to douche during the study; however, if douching does occur, 
the subject should wait to douche until at least six hours after the last act of intercourse and 
should record the product used as a concomitant medication in the eDiary. Similarly, subjects 
should be advised not to use any lubricants or vaginal preparations before or during intercourse. 
If use does occur, it should be recorded in the eDiary and as a concomitant medication. 
5.4 
Adverse Events 
5.4.1 
Collection of Adverse Events 
It is the responsibility of the Investigator to collect all AEs (both serious and non-serious) 
derived by spontaneous, unsolicited reports of subjects, by observation, and by routine open 
questionings, e.g., "How have you felt since I last saw you?" 
5.4.2 
Definitions 
For the purposes of this study, an AE is any unfavorable and unintended sign (including 
abnormal laboratory finding), symptom, or disease temporally associated with the use of the 
study drug, whether or not it is considered related.  


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 36 of 65 
 
All AEs, including intercurrent illnesses, occurring during the study will be documented in the 
EDC system. Illnesses that existed before entry into the study will not be considered AEs unless 
they worsen during the treatment period. All AEs, regardless of the source of identification  
(e.g., physical examination, laboratory assessment, reported by subject), must be documented. 
Pre-existing conditions will be recorded in the EDC system on the appropriate page (e.g., 
Medical History) 
AE data should be collected from enrollment until Visit 5 (14-30 days after the seventh study 
cycle) or early termination from the study. Those events that occur between the Screening Visit 
and enrollment will be analyzed as medical history. A treatment-emergent AE (TEAE) will be 
defined as an AE that begins or that worsens in severity after at least one dose of study drug has 
been administered. All AEs considered at least possibly related to study drug will be followed 
until resolution or, for chronic conditions, until deemed stable. 
5.4.3 
Assessment of Adverse Events 
Each AE will be assessed by the Investigator for seriousness, intensity, and causality using the 
following definitions: 
Seriousness 
A serious AE (SAE) is defined as any untoward medical occurrence that at any dose: 
• 
Results in death. 
• 
Is life-threatening; this means that the patient is at risk of death at the time of the event; it 
does not mean that the event hypothetically might have caused death if it were more 
severe. 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
• 
Results in persistent or significant disability or incapacity. 
• 
Is a congenital anomaly or birth defect. 
• 
Is an important medical event(s) that may not be immediately life-threatening or result in 
death or hospitalization but that may jeopardize the patient or require intervention to 
prevent the above 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 hospitalization; or development of drug dependency or drug abuse. 
Medical and scientific judgment should be exercised in deciding whether a case is serious and 
whether expedited reporting is appropriate. 
Intensity 
Investigators should assess the severity of AEs according to Common Terminology Criteria for 
Adverse Events (CTCAE) version 4.03. In general, CTCAE severity grades are: 
• 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 37 of 65 
 
• 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL) (Instrumental ADL refer to 
preparing meals, shopping for groceries or clothes, using the telephone, managing money, 
etc.) 
• 
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL (Self-care ADL refer to bathing, dressing and undressing, feeding self, using the 
toilet, taking medications, and not bedridden.) 
• 
Grade 4: Life-threatening consequences; urgent intervention indicated 
• 
Grade 5: Death related to AE 
Causality 
The Investigator will assess the causality/relationship between the study drug and the AE and 
record that assessment in the EDC system. The most likely cause of an AE (e.g., concomitant 
disease, concomitant medication, other) will be indicated in the EDC system with details of the 
concomitant disease or medication or other cause. 
The causal relationship of the AE to study drug will be described per World Health Organization 
(WHO) Uppsala Monitoring Centre (UMC) causality categories15: 
• 
Certain/Definite: 
o Event or laboratory test abnormality, with plausible time relationship to drug intake 
o Cannot be explained by disease or other drugs 
o Response to withdrawal plausible (pharmacologically, pathologically) 
o Event definitive pharmacologically or phenomenologically (i.e., an objective and 
specific medical disorder or a recognized pharmacological phenomenon) 
o Rechallenge satisfactory 
• 
Probable/Likely:  
o Event or laboratory test abnormality, with plausible time relationship to drug intake 
o Unlikely to be attributed to disease or other drugs 
o Response to withdrawal clinically reasonable 
o Rechallenge not required 
• 
Possible:  
o Event or laboratory test abnormality, with plausible time relationship to drug intake 
o Could also be explained by disease or other drugs 
o Information on drug withdrawal may be lacking or unclear 
• 
Unlikely: 
o Event or laboratory test abnormality, with a time to drug intake that makes a 
relationship improbable (but not impossible) 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 38 of 65 
 
o Disease or other drugs provide plausible explanations 
• 
Not assessable: 
o Report suggesting an adverse reaction 
o Cannot be judged because information is insufficient or contradictory 
o Data cannot be supplemented or verified 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 39 of 65 
 
Genitourinary Side Effects 
Genitourinary (GU) side effects (including vaginal burning, vaginal itching, vaginal pain, and 
other unexpected vaginal symptoms) will be collected in the eDiary each time the study drug is 
used and will be recorded at AEs. Subjects will note the time of drug administration, time of 
sexual intercourse and if they had any side effect (including severity, duration, and resolution).  
Unexpected vaginal bleeding or spotting will be recorded as AEs; however, expected menstrual-
related bleeding and/or spotting will not. 
Vulvar, Vaginal, or Cervical Side Effects 
An adaptation of the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and 
Pediatric Adverse Events, Version 2.0, Addendum 1 – Female Genital Grading Table for Use in 
Microbicide Studies will be used by the investigator to grade changes from baseline in vulvar, 
vaginal or cervical findings noted during the gynecologic exam and determine if they are 
considered significant, as defined as at least one grade increase from baseline.  These should be 
reported as AEs. The Female Genital Grading Table for Use in Microbicide Studies was 
developed for use in protocols involving topical application of products to the female genital 
tract.  Although developed specifically for microbicide studies, it is applicable to other protocols 
as well to ensure data consistency across sites.  
Table 3: 
Vulvar, Vaginal, or Cervical Individual Signs/Symptoms Grading Table 
Parameter 
Grade 0 
Normal 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Epithelial 
disruption 
None 
Blisters, 
ulcerations, 
superficial 
disruptions with 
minimal impact 
on life – no 
treatment needed 
Blisters, 
ulcerations, large 
disruptions – 
treatment 
indicated 
Severe epithelial 
disruption with 
hospitalization 
indicated 
Erythema 
None 
Erythema 
covering <50% 
of surface 
Erythema 
covering ≥50% 
of surface 
Severe erythema 
with 
hospitalization 
indicated 
Parameter 
Grade 0 
Grade 1 
Bleeding 
None 
Present 
Petechiae 
None 
Present 
Sloughing 
None 
Present 
 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 40 of 65 
 
Recording Adverse Events 
AE reporting will extend from enrollment until Visit 5 (14-30 days after the seventh study cycle). 
AEs occurring after Visit 5 should be reported to PAREXEL by the Investigator if the 
Investigator considers there is a causal relationship with the study drug. 
All AEs, regardless of the relationship to study drug, will be recorded in the EDC system. 
All AE reports should contain a brief description of the event, date and time of onset, date and 
time of resolution, intensity, treatment required, relationship to study drug, action taken with the 
study drug, outcome, and whether the event is classified as serious. 
AEs reported as ongoing at the last study visit will be listed as ongoing as of the last study date, 
and time of resolution will be marked as Not Applicable. 
5.4.4 
Reporting Serious Adverse Events 
The Investigator must report any SAEs to PAREXEL Medical Services within 24 hours of 
becoming aware of the event. 
The Investigator and the Sponsor/PAREXEL will review each SAE report and the 
Sponsor/PAREXEL will evaluate the seriousness and the causal relationship of the event to 
study treatment. In addition, the Sponsor/PAREXEL will evaluate the expectedness according to 
the Investigator Brochure. Based on the assessment of the event, a decision will be made 
concerning the need for further action. 
All SAEs will be recorded from enrollment until Visit 5. SAEs occurring after Visit 5 and 
coming to the attention of the Investigator must be reported only if they are considered (in the 
opinion of the Investigator) causally related to the investigational drug. 
Clinical sites should complete the SAE form and fax the documents to PAREXEL Medical 
Services using the PAREXEL SAE fax number below: 
(781) 434-5957 
or 
Complete the SAE report form and submit it to PAREXEL Medical Services via email using the 
email address below: 
NorthAmerica_Medical@parexel.com 
and/or 
If the clinical site is unable to complete the SAE form to report the event within 24 hours of its 
knowledge of the event, the Investigator may report the SAE over the telephone via the SAE 
answering service, and then provide the completed SAE form via fax/email. If questions arise 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 41 of 65 
 
regarding the reporting procedures or the specifics of the reporting of an event, sites may call the 
following number: 
(781) 434-5010 
5.4.5 
Follow-Up of Adverse Events 
All AEs experienced by a subject, deemed to be possibly related to study product, will be 
monitored until the AE has resolved.  Any abnormal laboratory values deemed to be possibly 
related to study product will be monitored until they have returned to baseline or stabilized at a 
level acceptable to the Investigator and Medical Monitor, until there is a satisfactory explanation 
for the changes observed, until the subject is lost to follow-up, or until the subject has died.  
5.4.6 
Pregnancy 
For the purposes of this study, pregnancy is not considered an AE. The pregnancy must be 
reported using the Pregnancy Notification Form to PAREXEL Medical Services within 24 hours 
of Investigator awareness (contact details in Section 5.4.4). Details on pregnancy determination 
and follow-up are provided in Section 6.6. Miscarriage is not considered an AE, unless meeting 
the SAE criteria (Section 5.4.3). 
5.5 
Questionnaires 
Questionnaires will be used to evaluate subject satisfaction with the study drug (Appendix C), 
subject sexual satisfaction (Appendix D-Appendix F), and pregnancy intendedness (Appendix G) 
in accordance with the schedule of assessments. 
5.6 
Electronic Diary 
Subjects will keep a daily eDiary to record coital information; study drug use information; use of 
concomitant medications, including other vaginal products and other contraceptives; menses; and 
sign and symptom data for the subject or as reported to her by her partner. If the subject has not 
completed the daily eDiary at any time, the site, PAREXEL, and the Sponsor will be notified via 
email, and the site will contact the subject for follow-up. Subjects will be allowed to 
retroactively enter data up to the predefined lock-out. Compliance reports will be available in 
real time and will be reviewed by the site at each visit, via telephone contact, and as needed 
based on eDiary alerts. 
6 STUDY CONDUCT 
6.1 
Deviation from the Protocol 
The Investigator should not deviate from the protocol except when necessary to protect the 
subject’s immediate safety or welfare. In the event that the Investigator or the subject deviates 
from the protocol, documentation should be provided to PAREXEL within two business days of 
Investigator awareness detailing the circumstances of the deviation. Certain protocol deviations 
may be considered as protocol violation and could require the subject to be terminated early from 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 42 of 65 
 
the study. It is the responsibility of the clinical sites to also report all protocol 
deviations/violations to their IRB as required under their IRB approval.  
6.2 
Protocol Approval and Amendment 
Before the start of the study, the study protocol and/or other relevant documents must be 
approved by an IRB. The site must document that all ethical and legal requirements have been 
met before the first subject is enrolled in the study. 
This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the Sponsor (and in many cases the FDA), and receive IRB approval prior 
to implementation as appropriate. Amendments cannot be implemented until the investigator is 
officially notified of the change by the Sponsor/PAREXEL. All amendments will be distributed 
to all investigational sites, with appropriate instructions for implementation. 
6.3 
Confidentiality 
All study findings and documents are confidential. The Investigator and members of his/her 
research team must not disclose such information without prior written approval from the 
Sponsor/PAREXEL. 
The anonymity of participating subjects must be maintained. During screening and after 
enrollment, coded subject numbers will be used to identify subjects in the EDC system and in 
other documents submitted to PAREXEL, and on all laboratory specimens in order to maintain 
subject confidentiality. Documents not to be submitted to PAREXEL that identify the subject 
(e.g., the signed ICF) must be maintained in confidence by the Investigator. 
6.4 
Discontinuation of Subjects 
A subject will be considered to have completed the study after she has completed seven on-study 
menstrual cycles (Section 3.3), the final visit has been performed, and the appropriate set of data 
has been collected and entered in the EDC system. A subject will be considered to have 
prematurely discontinued if she fails to remain in the study for seven on-study menstrual cycles 
and returns for Visit 5. Subjects who become pregnant while participating in the study are not 
considered to be discontinued unless they choose to no longer participate or are otherwise lost to 
follow up per Section 6.6. Subjects may withdraw from the study at any time without penalty and 
for any reason without prejudice to future medical care. 
Subjects must be discontinued from the study for any of the following reasons: 
• 
Withdrawal of consent 
• 
Emergence of condition(s) such that, in the opinion of the Investigator, continuation in 
the study would negatively impact the health of the subject or would jeopardize the 
validity of the data collected (e.g., development of a condition that would have prevented 
her entry into the study according to the inclusion or exclusion criteria that could affect 
the study data) 
• 
Any confirmed STI (other than HPV or trichomoniasis) 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 43 of 65 
 
• 
Subject lost to follow-up 
• 
If subject stops using study drug as her method of contraception 
• 
Study terminated (Section 6.5) 
Subjects may be discontinued prematurely from treatment for other reasons at the Investigator’s 
discretion. Investigators considering subject discontinuation should contact the 
Sponsor/PAREXEL to discuss the specific case prior to withdrawal of the subject. 
In all instances of premature discontinuation, the reason will be recorded in the EDC system. If 
withdrawal from the study is due to an AE, this information will also be recorded in the EDC 
system. In addition, all subjects who terminate early from the study will be asked to undergo the 
Treatment Exit Visit procedures (Section 5.1.4) regardless of the reason for discontinuation.  
Every effort must be made to follow up with subjects who terminate with a study drug-related 
AE(s) to determine the outcome of the AE(s).  
Subject Discontinuation Due to Non-Adherence 
Due to the risk of non-adherence-related pregnancy, subject discontinuation should be 
considered for non-adherence (unless a specific reason is given by the subject that can be 
corrected in the next cycle). Investigators considering subject discontinuation for the following 
reasons should contact the Sponsor/PAREXEL to discuss the specific case prior to withdrawal of 
the subject. 
1. Subjects with repeated failure over the course of one cycle to enter eDiary data, such that 
assessments of study medication compliance, sexual activity, and use of backup 
contraception are not possible. 
2. Subjects missing >50% doses/month for two consecutive months by self-report in eDiary. 
3. If an enrolled subject misses a scheduled appointment, she should be contacted within 
24 hours to reschedule the clinical site visit as soon as possible. After waiting one business 
day for the subject to respond, the clinical site should make additional attempt(s) to contact 
the subject. If the subject is not reached within two additional business days, a certified letter 
must be sent asking the subject to contact the clinical site. If the subject fails to respond 
within 24 hours after receipt of the certified letter is confirmed, she will be considered lost to 
follow-up and the last date of contact with the subject will be recorded as the date of 
discontinuation. The certified letter receipt will be filed with the Investigator’s copy of the 
subject’s source document. If the subject re-contacts the clinical site prior to being 
discontinued, and extenuating circumstances exist, the subject may be allowed to continue in 
the study with Sponsor/PAREXEL approval. 
4. For subjects with the following, the Investigator should discuss the specific circumstances 
leading to the event with the subject and Sponsor/PAREXEL: 
• 
Two consecutive cycles with no sexual activity 
• 
Two consecutive cycles with use of backup contraception 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 44 of 65 
 
6.5 
Premature Termination of the Study 
If the Investigator or the Sponsor/PAREXEL becomes aware of conditions or events that suggest 
the study poses a possible hazard to subjects, the study may be terminated after appropriate 
consultation among the relevant parties. The study may also be terminated early at the Sponsor’s 
discretion for reasons other than subject safety. 
Conditions that may warrant termination include, but are not limited to: 
• 
The discovery of a significant or unacceptable risk to the subjects enrolled in the study. 
• 
Failure to enroll subjects at an acceptable rate. 
• 
A decision on the part of the Sponsor to suspend or discontinue development of the study 
drug. 
6.6 
Pregnancy Determination/Pregnancy Review Committee 
If urine pregnancy testing performed at the clinical site during post-enrollment scheduled or 
unscheduled visits is positive, samples for serum quantitative β-hCG will be collected and sent 
for assessment by the central laboratory and pelvic examination for assessment of uterine size 
will be performed, preferably during the same study visit.  Pelvic ultrasound (transvaginal if <12 
weeks estimated gestation) will be performed as promptly as possible, preferably the same day as 
the positive urine pregnancy test is identified. The study drug must be discontinued immediately 
upon confirmation of a pregnancy, and the subject will remain in the study for pregnancy 
assessments. 
At enrollment, if the urine pregnancy test is negative and the serum β-hCG is borderline or 
positive, then the participant must be discontinued from the study and the reason for 
discontinuation will be protocol deviation, no pregnancy assessments as described below will be 
performed as part of the study, the pregnancy will not be followed, and the pregnancy will not be 
assessed by the Pregnancy Review Committee. 
Repeat evaluations (e.g., repeat ultrasound if initial ultrasound done prior to presence of 
gestational sac and/or crown rump length for dating) will be done as necessary to increase the 
accuracy of the determination of the estimated date of conception. Subjects who become 
pregnant while participating in the study should not be discontinued and, for those who choose to 
no longer participate or are lost to follow up, attempts should be made to continue to follow the 
pregnancy (up to three attempts followed by a certified letter), unless the Sponsor/PAREXEL has 
determined that sufficient information is available or will not become available. 
Any subject who reports a positive home pregnancy test must be evaluated at the site as soon as 
possible (e.g., the same day) for serum pregnancy testing, pelvic examination, and pelvic 
ultrasound (transvaginal if estimated gestational age is <12 weeks at the time of the visit). 
An independent expert Pregnancy Review Committee will review all confirmed pregnancies. 
Details of the membership and responsibilities of the Pregnancy Review Committee are defined 
in the Pregnancy Review Committee Charter. The Pregnancy Review Committee will determine 
if the pregnancy occurred on-treatment (defined as date of conception between enrollment to <8 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 45 of 65 
 
days after final study drug use) or not on-treatment (defined as date of conception prior to 
enrollment or after ≥8 days following final study drug use), or whether there is insufficient 
information for adjudication. 
For confirmed pregnancies, the date of conception will be assessed from the following: 
• 
First trimester transvaginal ultrasound (considered the most accurate; later ultrasounds 
will not be used for redating) 
• 
Estimate based on pelvic and/or abdominal examination or pregnancy outcome 
• 
eDiary information (e.g., last menstrual period and sexual activity) 
• 
Quantitative β-hCG determination 
• 
Urine hCG (date of last negative and first positive) 
• 
Investigator estimation in the absence of above criteria 
Subjects who become pregnant during the on-treatment period will be instructed to immediately 
stop use of study product, informed of pregnancy options, and referred for appropriate care. 
Subjects who become pregnant while participating in the study will be continued to be followed. 
If they are lost to follow-up, then attempts will be made to contact the subject as described above. 
Reports of pregnancy outcome will be requested by the Investigator from the attending physician 
or subject. Pregnancy outcome data will include the rates of spontaneous abortion, stillbirth, and 
live preterm and full-term births. If a subject has a spontaneous abortion or ectopic pregnancy 
this will not be considered as an AE or SAE unless it meets one of the SAE criteria indicated in 
Section 5.4.3. In addition, congenital malformations and anomalies will be recorded and 
summarized.  
7 STUDY MONITORING AND DOCUMENTATION 
7.1 
Clinical Monitoring, Quality Control, and Quality Assurance 
The Investigator is required to prepare and maintain adequate and accurate case histories 
designed to record all observations and other data pertinent to the study for each study 
participant. All information recorded in the EDC system for this study must be consistent with 
the subjects’ source documentation (i.e., medical records). 
The Investigator and Sub-Investigators will allow representatives from the Sponsor/PAREXEL 
direct access to all eCRFs, source documents, and corresponding portions of the medical records 
for each participant at mutually convenient times for periodic review during the study and after 
the study has been completed. The monitoring visits provide the opportunity to: 
• 
Initiate the clinical site. 
• 
Evaluate the progress of the study. 
• 
Verify the accuracy and completeness of the eCRFs/EDC system. 
• 
Ensure that all protocol requirements, applicable local regulations, and Investigators’ 
obligations are being fulfilled. 
• 
Resolve any inconsistencies in the study records. 
• 
Close out the study at the clinical site.  


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 46 of 65 
 
In addition to routine monitoring, site audits may be performed. The purpose of such audits will 
be to be to evaluate study conduct and compliance with the protocol, standard operating 
procedures (SOPs), GCP, and the applicable regulatory requirements. If an audit is performed, 
the clinical site must provide the auditors with direct access to all relevant records and 
documentation related to the study. 
8 DATA MANAGEMENT 
8.1 
Database Management and Quality Control 
All data generated by the clinical site personnel will be captured electronically at each study 
center using an EDC system. Data from external sources (such as laboratory data) will be 
imported into the database by the site. Once the clinical data have been submitted to the central 
server at the independent data center, changes to the data fields will be captured in an audit trail. 
The reason for change, the name of the person who performed the change, together with the time 
and date will be logged to provide an audit trail.  
If additional changes are needed or questions arise, PAREXEL will raise a query in the EDC 
system. The appropriate staff at the clinical site will answer queries sent to the Investigator. The 
name of the staff member responding to the query, and time and date stamp will be captured to 
provide an audit trail. Once all source data verification is complete and all queries are closed, the 
monitor will freeze the eCRF page. 
The specific procedures to be used for data entry and query resolution using the EDC system will 
be provided to the clinical site in a training manual. In addition, clinical site personnel will 
receive training on the EDC system. 
8.2 
Case Report Forms and Source Documentation 
All data obtained during this study should be entered in EDC system promptly. All source 
documents from which EDC entries are derived should be placed in the subject’s medical records. 
Measurements for which source documents are usually available include laboratory assessments. 
The original EDC entries for each subject may be checked against source documents at the 
clinical site during a monitoring visit or audit. 
After review by the site monitor, completed EDC entries will be forwarded to PAREXEL. 
Instances of missing or uninterpretable data will be discussed with the Investigator for resolution. 
8.3 
Data Collection 
The Investigators (and appropriately authorized staff) will be given access to an online web-
based EDC system. This system is specifically designed for the collection of the clinical data in 
electronic format. Access and right to the EDC system will be carefully controlled and 
configured according to each individual’s role throughout the study. In general, only the 
Investigator and authorized staff will be able to enter data and make corrections in the EDC 
system. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 47 of 65 
 
The EDC system should be completed for each subject included in the study and should reflect 
the latest observations on the subjects participating in the study. Therefore, the EDC entries are 
to be completed as soon as possible during or immediately after the subject’s visit or assessment. 
The Investigator must verify that all data entries in the EDC system are accurate and correct. If 
some assessments cannot be done, or if certain information is unavailable, not applicable or 
unknown, the Investigator should indicate this in the EDC system. 
Computerized data-check programs and manual checks will identify any clinical data 
discrepancies for resolution.  
8.4 
Study Documentation 
Investigators are responsible for assuring that the essential documents maintained in the Trial 
Master File at the clinical site are accurate and complete. 
8.5 
Data Processing 
The data-review and data-handling document provided to the site will include specifications for 
consistency and plausibility checks on data and will also include data-handling rules for obvious 
data errors. 
8.6 
Retention of Data 
The Investigator will maintain adequate records of the study, including in the EDC system, 
subjects’ medical records, laboratory reports, ICF, drug disposition records, safety reports, 
information regarding subjects who discontinued, and other pertinent data, for a minimum of 
2 years. The Investigator must contact the Sponsor for authorization prior to destruction of any 
such records, in the event of accidental loss or destruction, or to transfer the records to another 
location or to the Sponsor 
9 STATISTICAL AND ANALYTICAL METHODS 
The statistical considerations summarized in this section outline the plan for data analysis of this 
study. Further details will be provided in the Statistical Analysis Plan (SAP). 
9.1 
Outcome Evaluations 
Primary 
• 
The seven-cycle cumulative pregnancy rate as calculated using the KM method  
Secondary 
• 
Efficacy as measured by the Pearl Index 
Pearl Index = 
Number of Pregnancies * 365.25 * 100 
 
Total Number of Days Exposed 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 48 of 65 
 
• 
AEs 
• 
Pregnancy outcome 
Exploratory 
• 
Subject satisfaction  
• 
Sexual satisfaction  
• 
Pregnancy intendedness 
• 
Dosing time deviations for study drug-associated pregnancies 
9.2 
Sample Size 
The sample size determination assumes the following:  
• Study drug pregnancy percentage: 16.5% 
• 26.5% of subjects fail to qualify for the primary efficacy analysis population 
• Of the subjects that qualify for the primary efficacy analysis population, the average 
number of evaluable efficacy cycles per subject: 3.17 
• Exponential hazard for: 
o Pregnancy rate first 6 months: 16.5% 
o Drop out month 1: 10% 
o Drop out months 2-6: 38% 
With 1349 participants aged 18 through 35 years (inclusive), the study will have 90% power to 
ensure that the upper limit of the 95% CI of the cumulative seven-cycle pregnancy rate is less 
than or equal to 21%. The expected number of completers is 515 and the expected number of 
cycles evaluable for safety is at least 3143. 
9.3 
Analysis Populations 
The following subject populations will be created:  
• 
Intent-to-treat (ITT): All subjects enrolled into the study.  
• 
Safety population: ITT subjects who administer the study drug at least once  
• 
Modified intent-to-treat (MITT): Subjects must meet requirements 1, 2, and 
3 simultaneously, and at least one of requirement 4 or requirement 5 to be included in the 
MITT analysis population: 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 49 of 65 
 
1. Between 18 to 35 years of age (inclusive) at enrollment 
2. Had at least one report of pregnancy status after being enrolled; subjects with a 
positive serum pregnancy test at enrollment will not be included. 
3. ITT subjects whose diaries indicate they had at least one episode of coitus while using 
the study drug (also referred as “Typical-Use”) 
4. Had at least one cycle of eDiary without any backup contraception or EC 
5. Became pregnant and the pregnancy had a conception date that occurred between 
enrollment and <8 days after final study drug use 
• 
Efficacy-evaluable (EE): A subset of the MITT population that includes only those 
subjects whose diaries indicate that they used the study drug correctly for every act of 
intercourse for at least one menstrual cycle (also referred as “Perfect-Use” or 
“Per Protocol”). Cycles in which the study drug was used incorrectly for one or more 
coital acts will be removed, and the correct use cycles will be compressed to provide 
contiguous cycles of correct use.   
The MITT is the primary population for analysis of efficacy. Analyses in the EE population 
will be considered exploratory only. 
9.4 
Disposition of Subjects 
The number of subjects who are enrolled, treated, attended the various assessments, and who 
discontinue prematurely from or complete the study will be summarized.  
9.5 
Demographic and Pre-Treatment Characteristics 
Subject demographics and pre-treatment characteristics will be summarized descriptively.  
9.6 
Treatment Exposure 
Exposure to study drug will be summarized by the number of times the treatment is administered, 
the length of time over which the treatment is used, the number of times the study drug was used 
per cycle, and the number of cycles in the study. 
9.7 
Pre-Trial and Concomitant Medications 
Concomitant medications include any medication or health product taken during the active study 
treatment period. Pre-trial medications include any medications taken within 60 days of 
enrollment, and for one year in the case of contraceptives. The number and percentage of 
subjects using medications, as captured on the Concomitant Medication eCRF Form, will be 
tabulated for the safety population. There will be separate tables for pre-trial and concomitant 
medications. Subjects taking a medication more than once will be only counted once for that 
medication. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 50 of 65 
 
9.8 
Analyses of Pregnancy Experience 
9.8.1 
Primary Efficacy Analysis 
The primary efficacy endpoint is the seven-cycle cumulative pregnancy rate as calculated using 
the KM method. The KM estimate and its 95% CI (based on Greenwood’s method) of the seven-
cycle cumulative pregnancy probability of women in the MITT population will be calculated.   
9.8.1.1 
Derivation of the Primary Variable 
The primary variable is the number of cycles from enrollment to the first pregnancy within 
seven cycles, which will be derived in the following steps:  
• Imputing the missing dates of cycles: If the eDiary has partial dates for the start/end of a 
cycle, then the dates will be imputed to be a full date (when possible) based on the 
start/end dates of cycles that occurred before and after that cycle with partial dates. If 
multiple cycles in a row occur with partial start/end dates, then it will be assumed the 
cycles were equal length in order to determine the imputed start/end dates of the cycle. 
• Determining the evaluable cycles: Cycles must meet all conditions given below to be 
considered evaluable cycles: 
o Cycles 0-6 for subjects who are enrolled for at least 21 days prior to the start of 
her next menses, or Cycles 1-7 for subjects who are enrolled in less than 21 days 
prior to the start of her next menses;  
o Cycles that are indicated by the eDiary that no backup contraception or EC are 
used or in which subjects are pregnant; 
o Cycles with length within the range of 21 days to 35 days or in which subjects are 
pregnant.  
o For EE analyses, cycles in which the eDiaries indicate that study drug was used 
correctly for every act of intercourse during that cycle. 
• Compressing the evaluable cycles: Evaluable cycles will be compressed to form 
contiguous evaluable cycles for each subject sequentially. 
• Determining the date of conception:  
o The Pregnancy Review Committee will review all confirmed pregnancies and 
determine if the pregnancy occurred on-treatment (defined as date of 
conception between enrollment to <8 days after final study product use) or not 
on‑treatment (defined as date of conception prior to enrollment or after 7 days 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 51 of 65 
 
following final study product use), or whether there is insufficient information 
for adjudication. 
For confirmed pregnancies, the date of conception will be assessed from the 
following: 
 First trimester transvaginal ultrasound (considered the most accurate; 
later ultrasounds will not be used for redating) 
 Estimate based on pelvic and/or abdominal examination or pregnancy 
outcome 
 eDiary information (e.g., last menstrual period and sexual activity) 
 Quantitative β-hCG determination 
 Urine hCG (date of last negative and first positive) 
 Investigator estimation in the absence of above criteria 
• Determining of censoring for cycles to pregnancy: Subjects will be censored from 
analysis at the earliest of: 
o The estimated date of conception that occurred between enrollment and <8 days 
after final study drug use 
o The last date at which pregnancy status was known 
o The conclusion of her seventh cycle on-treatment (up to a total of 245 days [or 
294 days for the sensitivity analysis, allowing a cycle length range of 21 to 
42 days]) 
9.8.2 
Secondary Analysis 
Secondary Efficacy Analysis as Measured by the Pearl Index: The Pearl Index and its 95% CI for 
the MITT population will be calculated. The Pearl Index will be calculated as the percentage of 
the total number of pregnancies versus the total number of days exposed. The 95% CI will be 
calculated using normal approximation. 
9.8.3 
Sensitivity Analyses 
Sensitivity Analysis with Respect to the Cycle Range: The primary analysis will be repeated with 
the cycle length expanded from 21-35 days to 21-42 days.  
Sensitivity Analysis of the Dosing Time with Respect to Sexual Intercourse: To evaluate the 
effect of the dosing time with respect to sexual intercourse, subgroup analyses for the primary 
analysis will be performed by the dosing time category performed according to the following 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 52 of 65 
 
dosing time categories with respect to sexual intercourse: < 1 hour, < 1.5 hour, < 2 hours, <2.5 
hours, and all cycles (without respect to dosing time).  
Sensitivity Analysis with Respect to Completers and Non-completers: To evaluate differences 
between completers and non-completers the primary analysis will be repeated for just completers. 
A completer is defined as a woman who becomes pregnant within 7-cycles (inclusive) or who 
completes the 7 cycles with no pregnancy. 
9.9 
Safety Parameters 
The safety population will be used for all safety summaries. All safety data will be summarized 
descriptively.  
9.9.1 
Incidence of Adverse Events 
The number (percentage) of subjects with at least one AE will be presented in a frequency table 
by MedDRA system organ class and per MedDRA “preferred” term. A similar summary will be 
created for SAEs and AEs leading to discontinuation of study drug use. Summaries will also be 
presented by relationship to study drug and intensity of AE. 
9.9.2 
Other Safety Assessments 
Changes in other safety parameters such as hematology and clinical chemistry, vital signs, 
physical examination, gynecological exam, and pregnancy outcome follow up will be 
summarized using descriptive statistics as appropriate. 
9.10 
Other Endpoints 
9.10.1 
Subject Satisfaction 
Subject satisfaction with the study drug and subject sexual satisfaction will be summarized using 
frequency and percentage.  
9.10.2 
Pregnancy Intendedness 
Pregnancy intendedness scale results and change from baseline will be summarized descriptively. 
9.11 
Protocol Deviations 
Deviations from the protocol, including violations of inclusion/exclusion criteria, will be 
assessed in cooperation with the Sponsor and summarized. Subjects whose diaries indicate that 
they used the assigned study drug incorrectly for every act of intercourse for every menstrual 
cycle will be excluded from the EE population. Cycles in which the study drug was used 
incorrectly for one or more coital acts will be removed, and the correct use cycles will be 
compressed to provide contiguous cycles of correct use. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 53 of 65 
 
9.12 
Computer Methods 
Version 9.3 or later of the SAS® statistical software package will be used to produce all 
summaries, listings, statistical analyses, and graphical presentations.   
10 REVISION HISTORY 
Table 4: 
Summary of Amendments 
Version 
Number 
Effective Date 
Summary of Changes 
1 
05 May 2017 
Original Protocol 
2 
08 June 2017 
Section 4.1.3: Moved Partner Requirements from the inclusion/exclusion 
criteria to the screening procedures based on IRB comments 
Clarifications to partner information collection throughout 
3 
19 June 2017 
Section 5.4.3: Added grading criteria for valvar, vaginal or cervical AEs  
Section 5.6: Lock-out period statement added for eDiary 
Section 6.6: Corrected typo in “on-treatment” definition  
Section 9.1: Revised the Pearl Index formula 
Section 9.2: Sample size increased from 1157 (85% power) to 1349 
(90% power) 
Section 9.8.3: Added an additional sensitivity analysis 
Table 1: Clarified footnote “a” 
4 
01 Nov 2017 
Section 6.4 – Clarified that subjects who become pregnant are not 
discontinued 
Section 9.2 – Updated the expected number of completers and evaluable 
cycles for 1394 participants 
Section 9.8.3 - Adjusted dosing time intervals 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 54 of 65 
 
11 REFERENCES 
 
1. Guttmacher Institute. Unintended pregnancy in the United States. Available at: 
https://www.guttmacher.org/fact-sheet/unintended-pregnancy-united-states. Accessed 
December 16, 2016. 
2. Trussell J, Henry N, Hassan F, Prezioso A, Law A, Filonenko A. Burden of unintended 
pregnancy in the United States: potential savings with increased use of long-acting 
reversible contraception. Contraception. 2013;87(2):154-161. 
3. Mansour D. International survey to assess women's attitudes regarding choice of daily 
versus nondaily female hormonal contraception. Int J Womens Health. 2014;6:367-375. 
4. Chacko MR, Wiemann CM, Buzi RS, Kozinetz CA, Peskin M, Smith PB. Choice of 
postpartum contraception: factors predisposing pregnant adolescents to choose less 
effective methods over long-acting reversible contraception. J Adolesc Health. 
2016;58(6):628-635. 
5. Acidform vaginal gel. Investigator's brochure. March 8, 2016. 
6. Garg S, Anderson RA, Chany CJ, et al. Properties of a new acid-buffering bioadhesive 
vaginal formulation (ACIDFORM). Contraception. 2001;64(1):67-75. 
7. Shortridge E, Miller K. Contraindications to oral contraceptive use among women in the 
United States, 1999-2001. Contraception. 2007;75(5):355-360. 
8. Lauring JR, Lehman EB, Deimling TA, Legro RS, Chuang CH. Combined hormonal 
contraception use in reproductive-age women with contraindications to estrogen use. Am 
J Obstet Gynecol. 2016;215(3):330.e1-7. 
9. Williams DL, Newman DR, Ballagh SA, et al. Phase I safety trial of two vaginal 
microbicide gels (Acidform or BufferGel) used with a diaphragm compared to KY jelly 
used with a diaphragm. Sex Transm Dis. 2007;34(12):977-984. 
10. Anderson DJ, Williams DL, Ballagh SA, et al. Safety analysis of the diaphragm in 
combination with lubricant or acidifying microbicide gels: effects on markers of 
inflammation and innate immunity in cervicovaginal fluid. Am J Reprod Immunol. 
2009;61(2):121-129. 
11. von Mollendorf CE, Van Damme L, Moyes JA, et al. Results of a safety and feasibility 
study of the diaphragm used with ACIDFORM Gel or K-Y Jelly. Contraception. 
2010;81(3):232-239. 
12. Frohwirth L, Blades N, Moore AM, Wurtz H. The complexity of multiple contraceptive 
method use and the anxiety that informs it: implications for theory and practice. Arch Sex 
Behav. 2016;45(8)2123-2135. 
13. World Medical Association. World Medical Association Declaration of Helsinki. 
Recommendations guiding physicians in biomedical research involving human subjects. 
JAMA. 1997;277(11):925-926. 
14. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment 
guidelines, 2015. MMWR Morb Mortal Wkly Rep. 2015; 
15. World Health Organization-Uppsala Monitoring Centre. The use of the WHO-UMC 
system for standardized case causality assessment. Available at: http://who-
umc.org/Graphics/24734.pdf. Accessed December 22, 2016. 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 55 of 65 
 
12 APPENDICES 
Appendix A: 
Investigator Obligations 
This clinical research study is subject to the regulations of the FDA. The responsibilities imposed 
upon Investigators by the FDA are summarized in the “Statement of Investigator Form” 
(Form FDA 1572). This form summarizes the qualifications of each Investigator, his or her 
obligations in carrying out the research protocol, and expresses his or her willingness to follow 
FDA regulations with respect to this study. 
The Investigator agrees to assume the following responsibilities and signifies his or her 
agreement by signing the Form FDA 1572: 
• 
To secure prior approval of the study by an appropriate IRB. This board should be 
constituted in conformity with FDA regulations. 
• 
To report on the progress of the study to the IRB and to submit a final report within three 
(3) months of the conclusion of data collection. 
• 
To maintain current records of the receipt, dispensing, and disposition of study drug and 
to return all unused drug to the Sponsor or the Sponsor’s designated agent. 
• 
To obtain a valid, fully informed, freely given written consent from each subject who 
participates in the study. 
• 
To prepare and maintain adequate case histories of all subjects entered into the study, 
including web-based eCRFs, hospital records, laboratory results, and lab records, and to 
store these case histories for a minimum of two years following notification by the 
Sponsor that all investigations have been discontinued or that the FDA has approved the 
drug or device application. 
• 
To identify all Sub-Investigators who will also supervise drug administration or device 
implantation. 
• 
To report all AEs/SAEs to the Sponsor or designated agent per Section 5.4. 
• 
To allow inspection or copying by the FDA, Sponsor, or Sponsor’s designated agent of 
case histories and records of drug distribution. 
 
 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 56 of 65 
 
Appendix B: 
CBC with Differential and Clinical Chemistry 
The following central laboratory evaluations will be conducted on blood samples collected per 
the schedule of assessments: 
CBC  
Clinical Chemistry 
Basophils (absolute count and %) 
Eosinophils (absolute count and %) 
Hemoglobin 
Hematocrit 
Lymphocytes (absolute count and %) 
Mean corpuscular volume (MCV) 
Mean corpuscular hemoglobin (MCH) 
Mean corpuscular hemoglobin concentration 
(MCHC) 
Monocytes (absolute count and %) 
Neutrophils (absolute count and %) 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase (AST) 
Bicarbonate 
Blood urea nitrogen (BUN) 
Calcium 
Chloride 
Cholesterol 
Glucose 
Lactate dehydrogenase (LDH) 
Phosphorus 
Platelet count 
Red blood cell (RBC) 
Potassium 
Total Protein 
White blood cell (WBC) 
Total Bilirubin 
 
Sodium 
 
Uric acid 
 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 57 of 65 
 
Appendix C: 
Subject Satisfaction with Study Drug 
 
Baseline: 
 
How satisfied were you with your most recent birth control method? 
a. Very satisfied 
b. Satisfied 
c. Somewhat satisfied 
d. Somewhat dissatisfied 
e. Dissatisfied 
 
 
Study Visits 3-5: 
 
How satisfied are you with your study birth control method? 
a. Very satisfied 
b. Satisfied 
c. Somewhat satisfied 
d. Somewhat dissatisfied 
e. Dissatisfied 
 
How likely is it that you would recommend this method to a friend who is considering a vaginal 
contraceptive gel? 
a. Very likely 
b. Likely 
c. Somewhat likely 
d. Somewhat unlikely 
e. Unlikely 
 
How likely is it that you would recommend this method to a friend who is considering another 
birth control option? 
a. Very likely 
b. Likely 
c. Somewhat likely 
d. Somewhat unlikely 
e. Unlikely 
 
How likely would you be to continue this method if it were available after the study? 
a. Very likely 
b. Likely 
c. Somewhat likely 
d. Somewhat unlikely 
e. Unlikely 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
Page 58 of 65 
 
Appendix D: 
Subject Sexual Satisfaction 
 
Baseline: 
 
What impact did your most recent contraceptive method have on your sex life in the last 4 weeks 
of use? 
a. My sex life was a lot better than before  
b. My sex life was a little better than before  
c. My sex life was no different than before  
d. My sex life was a little worse than before  
e. My sex life was a lot worse than before 
 
 
Study Visits 3-5: 
 
What impact has the study contraceptive method had on your sex life since your last study visit? 
a. My sex life is a lot better than before  
b. My sex life is a little better than before  
c. My sex life is no different than before  
d. My sex life is a little worse than before  
e. My sex life is a lot worse than before 
 
 


AMPHORA® 
 
Protocol: AMP002 
Evofem, Inc. 
 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 59 of 65 
Appendix E: 
Sexual Function Questionnaire 
How frequently in the PAST MONTH have you had the problems listed below?* 
ALSO, MARK THE BOX IN THE LAST COLUMN if the problem stops your sexual activity. 
 
 
 
Not at all 
Seldom,  
less than 
25% of the 
time 
Sometimes, 
about 50% 
of the time 
Usually, 
about 75% 
of the time 
Always 
MARK THE BOX 
IF THE 
PROBLEM 
STOPS YOUR 
SEXUAL 
ACTIVITY 
a. 
Vaginal dryness during sexual activity 
1 
2 
3 
4 
5 
☐ 
b. 
Lack of sexual interest or desire 
1 
2 
3 
4 
5 
☐ 
c. 
Vaginal tightness 
1 
2 
3 
4 
5 
☐ 
d. 
Pain during penetration or intercourse 
1 
2 
3 
4 
5 
☐ 
e. 
Anxiety about your sexual performance 
1 
2 
3 
4 
5 
☐ 
f. 
Unable to orgasm 
1 
2 
3 
4 
5 
☐ 
g. 
Vaginal bleeding or irritation from 
penetration or intercourse 
1 
2 
3 
4 
5 
☐ 
h. 
Increased sensitivity of your skin to 
intimate touching 
1 
2 
3 
4 
5 
☐ 
i. 
Sharp pain inside or outside your vagina 
1 
2 
3 
4 
5 
☐ 
j. 
Other problem with sexuality;  
Please specify: 
1 
2 
3 
4 
5 
☐ 
*Source: Question 10, Sexual Function Questionnaire, Fred Hutchinson Cancer Research Center. 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 60 of 65 
 
Appendix F: 
Female Sexual Function Index 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 61 of 65 
 
 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 62 of 65 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 63 of 65 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 64 of 65 
 
 
 


AMPHORA® 
Protocol: AMP002 
Evofem, Inc. 
Version 4 – 01 Nov 2017 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 65 of 65 
 
Appendix G: 
Pregnancy Intendedness 
 
1. At baseline and all in-person study visits: 
On a scale of 1-10 (Very unhappy to Very happy), how would you feel if you were to get 
pregnant? 
2. If a subject becomes pregnant at any time during the study: 
On a scale of 1-10 (Very unhappy to Very happy), how do you feel about your pregnancy? 
 
 

SAP_001.pdf: 
AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 1 of 39 
 
STATISTICAL ANALYSIS PLAN AMP002 
Title: 
AMPOWER 
A SINGLE-ARM, PHASE III, OPEN-LABEL, 
MULTICENTER, STUDY IN WOMEN AGED 18 TO 35 
YEARS OF THE CONTRACEPTIVE EFFICACY AND 
SAFETY OF AMPHORA® CONTRACEPTIVE VAGINAL 
GEL 
Protocol Number: 
AMP002 
Sponsor: 
Evofem, Inc. 
12400 High Bluff Dr., Suite 600 
San Diego, CA 92130 
Phone: 
(858) 550-1900 
Fax: 
(844) 828-2010 
Clinical Research 
Organization: 
 Health Decisions 
 2510 Meridian Parkway 
 Durham, NC 27713-2260 
 Phone:  919-967-1111 
 Fax: 
(781) 487-0525 919-967-1145 
Statistical Analysis Plan 
Version: 
 Version 5 – 24 October 2018 
 
 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 2 of 39 
 
 
 
 
Title: 
AMPOWER 
 
A SINGLE-ARM, PHASE III, OPEN-LABEL, MULTICENTER, 
STUDY IN WOMEN AGED 18 TO 35 YEARS OF THE 
CONTRACEPTIVE EFFICACY AND SAFETY OF AMPHORA® 
CONTRACEPTIVE VAGINAL GEL 
Protocol Number: 
 
AMP002 
IND Number: 
 
109300 
Clinical Phase: 
 
III 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 4 of 39 
 
 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE .............................................................3 
1 INTRODUCTIO N..................................................................................................................9 
2 STUDY OBJECTIVES...........................................................................................................9 
2.1 
Primary Objective.................................................................................................9 
2.2 
Secondary Objective..............................................................................................9 
2.3 
Exploratory Objectives ..........................................................................................9 
2.4 
Primary Endpoint .................................................................................................9 
2.5 
Secondary Endpoints ............................................................................................9 
2.6 
Exploratory Endpoints ..........................................................................................9 
3 INVES TIGATIONAL PLAN ............................................................................................... 10 
3.1 
Overall Study Design and Plan............................................................................. 10 
3.2 
Schedule of Assessments ...................................................................................... 11 
4 STATISTICAL METHODS ................................................................................................. 14 
4.1 
Data Quality Assurance....................................................................................... 14 
4.2 
General Presentation Considerations.................................................................... 14 
4.3 
Analysis Populations............................................................................................ 15 
4.4 
Study Subjects.................................................................................................... 16 
4.4.1 Disposition of Subjects ............................................................................................... 16 
4.4.2 Study Protocol Deviations .......................................................................................... 16 
4.5 
Demographic and Pre-Treatment Characteristics................................................ 16 
4.5.1 Demographic ............................................................................................................. 16 
4.5.2 Gynecological History ................................................................................................ 16 
4.5.3 Contraception Use History.......................................................................................... 17 
4.5.4 Obstetric History ....................................................................................................... 17 
4.5.5 Medical History ......................................................................................................... 17 
4.5.6 Pre-Treatment Signs and Symptoms ............................................................................ 17 
4.5.7 Prior and Concomitant Medications ............................................................................ 18 
4.6 
Treatment Compliance and Study Instruction Departures ..................................... 18 
4.7 
Efficacy Evaluation ............................................................................................. 20 
4.7.1 Analysis and Data Conventions ................................................................................... 20 
4.7.1.1 
Definition of Baseline ........................................................................................... 20 
4.7.1.2 
Definition of Cycle ............................................................................................... 20 
4.7.1.3 
Multiple Comparisons/Multiplicity....................................................................... 21 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 5 of 39 
 
4.7.1.4 
Interim Analyses ................................................................................................. 21 
4.7.2 
Primary Efficacy Analysis ................................................................................... 21 
4.7.2.1Derivation of the Primary Endpoint ............................................................................ 21 
4.7.3 
Secondary Efficacy Analyses................................................................................ 23 
4.7.3.1Sensitivity Analysis with Respect to the Cycle Range .................................................... 23 
4.7.3.2Sensitivity Analysis with Respect to the Dosing Time with Respect to Sexual Intercourse 23 
4.7.3.3Perfect-Use 7-Cycle Pregnancy Probabilities ................................................................ 23 
4.7.3.4Pearl Rates from 7-Cycle Data .................................................................................... 23 
4.7.3.5Summary of Number of Diary Cycles and Cycles Excluded from EE Population ............ 24 
4.8 
Safety Evaluation ................................................................................................ 24 
4.8.1 Treatment Exposure .................................................................................................. 24 
4.8.2 Adverse Events .......................................................................................................... 25 
4.8.3 Genitourinary Side Effects .......................................................................................... 25 
4.8.4 Gynecological Infections ............................................................................................. 26 
4.8.5 Dipstick Urinalysis and Urine Culture ......................................................................... 26 
4.8.6 Gynecological Examination ........................................................................................ 27 
4.8.7 Sexually Transmitted Infection Tests........................................................................... 27 
4.8.8 Clinical Laboratory Evaluation ................................................................................... 27 
4.8.9 Vital Signs ................................................................................................................. 27 
4.8.10 Pregnancy Outcome.................................................................................................... 27 
4.9 
Subject Satisfaction ............................................................................................. 28 
4.9.1 Subject Satisfaction Questionnaires ............................................................................ 28 
4.9.2 Sexual Function Questionnaire ................................................................................... 30 
4.9.3 Sexual Satisfaction and Lubrication ............................................................................ 30 
4.10 
Missing Data Handling ..................................................................................... 31 
4.10.1 Imputing partial AE and prior/concomitant medication start dates ............................... 31 
4.10.2 Imputing partial AE and prior/concomitant medication stop dates ................................ 32 
4.11 Pregnancy Intendedness.................................................................................................... 32 
4.11.1 Determination of Sample Size ..................................................................................... 32 
5 
Appendix............................................................................................................................. 33 
5.1 
Grading for Vulvar, Vaginal, or Cervical Findings ................................................ 33 
6 PROPOSED TABLES, FIGURES AND LISTINGS.................................................................... 34 
6.1 
Proposed Tables and Figures ............................................................................... 34 
6.2 
Proposed Data Listings........................................................................................ 37 
7 
REFERENCES .................................................................................................................... 39 
 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 6 of 39 
 
 
 
 
LIST OF TABLES 
 
Table 1: Study Assessment and Procedures....................................................................................... 11 
Table 2: Handling Rules of the Analysis Populations for Special Situations ........................................... 15 
Table 3: Sexual Function Questionnaire Outcomes and Coding ........................................................... 30 
 
 
LIST OF FIGURES 
 
Figure 1: Study Visit Timing Based on Menstrual Cycle at Enrollment ................................................. 13 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 7 of 39 
 
 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse Event 
BV 
Bacterial Vaginosis 
CBC 
Complete Blood Count 
CI 
Confidence Interval 
EC 
Emergency Contraception 
eCRF 
Electronic Case Report Form 
EE 
Efficacy Evaluable 
FDA 
The U.S. Food and Drug Administration 
FSD 
Female Sexual Dysfunction 
FSFI 
Female Sexual Function Index 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
ICH 
International Council for Harmonization of Technical Requirements 
for Pharmaceuticals for Human Use 
in 
Inch 
ITT 
Intent-To-Treat 
IUD 
Intrauterine Device 
kg 
Kilogram 
KM 
Kaplan-Meier 
lb 
Pound 
m 
meter 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
MITT 
Modified Intent-to-Treat 
mL 
Milliliter 
N-9 
Nonoxynol-9 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 8 of 39 
 
 
Abbreviation 
Definition 
SE 
Standard Error 
STI 
Sexually Transmitted Infection 
SOC 
System-Organ Class 
US 
United States 
UTI 
Urinary Tract Infection 
VCAS 
Virtual Clinical Adjudication System 
WBC 
While Blood Cell 
WHO 
World Health Organization 
 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 9 of 39 
 
1 INTRODUCTION 
This Statistical Analysis Plan (SAP) for AMP002, Version FINAL describes the statistical 
methods to be used during the analyses and reporting of data collected under Phase 3 AMP002 
Protocol, dated 01 November 2017. The planned analyses identified in this SAP may be included 
in the clinical study report (CSR), any regulatory submissions, or future manuscripts. Post-hoc 
exploratory analyses not identified in this SAP may also be performed to further examine study 
data and will be clearly identified as such in the final CSR. 
This SAP is based upon the following study documents: 
• AMP002-231564_Protocol SN0051_Version 4.0_dated 01-NOV-2017 
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the U.S. Food and Drug Administration (FDA) and International Council for 
Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). 
2 STUDY OBJECTIVES 
2.1 Primary Objective 
• To evaluate the contraceptive efficacy of Amphora over seven cycles of use 
2.2 Secondary Objective 
• To evaluate the contraceptive efficacy of Amphora as measured by the Pearl Index 
• To evaluate the safety of Amphora over seven cycles of use 
• To assess pregnancy outcomes 
2.3 Exploratory Objectives 
• To assess subject satisfaction (including sexual satisfaction) with Amphora over seven 
cycles of use 
• To assess pregnancy intendedness for subjects treated with Amphora over seven cycles of 
use 
• To assess dosing time deviations for study drug-associated pregnancies 
2.4 Primary Endpoint 
• Seven-cycle cumulative pregnancy rate as calculated using the Kaplan-Meier (KM) method 
2.5 Secondary Endpoints 
• Efficacy measured by the Pearl Index 
• Adverse events (AEs) 
• Pregnancy outcomes 
2.6 Exploratory Endpoints 
• Subject satisfaction 
• Sexual satisfaction 
• Pregnancy intendedness 
• Dosing time deviations for study drug-associated pregnancies 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 10 of 39 
 
 
3 INVESTIGATIONAL PLAN 
3.1 Overall Study Design and Plan 
The proposed study design is a single-arm, open-label, Phase III study in approximately 100 sites 
in the US over seven cycles of use in women aged 18 to 35 years who are at risk of pregnancy. 
The primary endpoint is the seven-cycle cumulative pregnancy rate as calculated using the 
Kaplan-Meier (KM) method. Secondary endpoints proposed include efficacy as measured by the 
Pearl Index, AEs, and pregnancy outcomes. In addition, exploratory endpoints proposed include 
subject satisfaction, sexual satisfaction, pregnancy intendedness, and dosing time deviations for 
Amphora and associated pregnancies. 
Through assessments including medical and gynecological history, pelvic examination, and 
laboratory procedures, subjects will be screened for eligibility in order to enroll approximately 
1350 subjects into the study. After a screening period of up to 60 days, enrolled women will 
receive study drug. Each woman will participate in the study until she has completed seven 
study cycles. Women who have individual cycles that do not meet the criteria for an evaluable 
cycle will not have those cycles replaced by subsequent cycles in order to provide a total of 
seven evaluable cycles. 
Subjects will be expected to attend five visits: Screening (Visit 1), Enrollment (Visit 2), Visit 3 
(during the second study cycle), Visit 4 (during either the fifth or sixth study cycle), and Visit 5 
(14 to 30 days after seventh study cycle). In addition, subjects will be contacted by telephone by 
the clinical site staff during study cycle 3 or 4 to monitor AEs, concomitant medications, sexual 
activity, use of backup contraception, compliance with use of the study drug and electronic 
diary (eDiary), need for an unscheduled visit, and confirmation of contact information. In the 
event that the subject reports any significant gynecological symptoms or any symptoms 
indicative of a possible UTI, or vaginal infection, she will be asked to contact the clinical site 
for possible evaluation. During further unscheduled safety visits, the Investigator may perform 
a gynecological exam and appropriate laboratory tests, and provide appropriate treatment as 
necessary. 
Table 1 presents an overview of the study assessments and procedures. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 11 of 39 
 
3.2 Schedule of Assessments 
Table 1: Study Assessment and Procedures 
 
Visit 1 
Visit 2 
Visit 3 
Telephone Visit 
Between Visits 3 and 4 
Visit 4 
Visit 5b 
Procedures 
Screening 
Day -60 to 0 
Enrollment 
Cycle 0 
(During 2nd 
Study Cycle)a 
(During Either 3rd or 4th 
Study Cycle) 
(During Either 5th 
or 6th Study Cycle) 
14-30 Days After 7th 
Study Cycle/ Exit Visit 
Written Informed Consent/HIPAA 
X 
 
 
 
 
 
Eligibility (Inclusion/Exclusion)  
X 
X 
 
 
 
 
Medical/Gynecological Historyc 
X 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Enrollment 
 
X 
 
 
 
 
Prior History of Contraceptive Use 
(Past Year) 
X 
X 
 
 
 
 
Pre-Trial Medications 
X 
X 
 
 
 
 
Vital Signsd  
X 
X 
X 
 
X 
X 
CBC with Differential and Chemistrye 
X 
 
 
 
 
X 
HIV Teste 
X 
 
 
 
 
 
Physical Examinationf 
X 
 
 
 
 
X 
Gynecological Examinationg 
X 
X 
X 
 
X 
X 
Pap Test 
Xh 
 
 
 
 
 
Chlamydia/Gonorrhea Test 
X 
 
Xi 
 
Xi 
Xi 
Urine Culturej 
X 
 
 
 
 
X 
Dipstick Urinalysisk 
Xl 
X 
X 
 
X 
Xl 
Urine Pregnancy Testm 
X 
X 
X 
 
X 
X 
Serum Pregnancy Test 
 
X 
 
 
 
X 
Distribute eDiaryn 
 
X 
 
 
 
 
Review eDiaryn 
 
 
X 
X 
X 
X 
Dispense/Return Study Product 
 
Xo 
X 
 
X 
X 
Subject Satisfaction with Study 
Product Questionnaire 
 
X 
X 
 
X 
X 
Sexual Satisfaction Questionnaire 
 
X 
X 
 
X 
X 
Pregnancy Intendedness Questionnaire 
 
X 
X 
 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
Concomitant Medications 
 
X 
X 
X 
X 
X 
Between-Visit Contactp 
 
 
 
X 
 
 
Schedule Next Visit/Contactq 
Xr 
X 
X 
X 
X 
 
Post-Study Treatment Contraceptions  
 
 
 
 
X 
X 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 12 of 39 
 
 
Abbreviations: BV=bacterial vaginosis; CBC=complete blood count; eDiary=electronic diary; HIPAA=Health Insurance Portability and Accountability Act; HIV=human 
immunodeficiency virus; Pap test=Papanicolaou test; Tel=telephone contact; UTI=urinary tract infection. 
a. The time period between Visit 2 and Visit 3 will vary based subject’s first on-study cycle as defined in Figure 1. 
b. Treatment will end after seven study cycles. The cycle at enrollment will be included as one of the seven study cycles only if the time from enrollment to the start of the next 
menstrual period was ≥21 days. 
c. Includes documentation of the start date of last menstrual period. 
d. Height, weight, and blood pressure will be measured at Screening. Only weight and blood pressure will be measured at subsequent visits. 
e. Central laboratory will analyze CBC with differential, chemistry panels, and perform HIV test and chlamydia and gonorrhea assessments at Screening. Urine microscopy 
and culture and Pap tests will be performed locally. 
f. Physical examination to include assessment of heart, lungs, and abdomen, and a breast examination at the discretion of the Investigator.  
g. Gynecological examination is to include a speculum and bimanual examination. Investigators will note the presence or absence of vulvar, vaginal, or cervical findings, 
including epithelial disruption, or areas of obvious erythema; these will be assessed as either not present, mild, moderate, or severe; the presence or absence of bleeding, 
petechiae, or sloughing will also be recorded. Clinically significant changes from Baseline as judged by the Investigator are to be reported as AEs. If a woman experiences 
any significant gynecological symptoms, she should return to the clinical site as soon as possible for a gynecological examination. Wet mount and vaginal pH for monilia, 
BV, and trichomonas will be performed only for symptomatic women.  
h. Results from a Pap test performed at the screening clinical site ≤12 months prior to the Screening Visit may be used provided the report is available. 
i. Chlamydia and gonorrhea assessments to be performed at Visits 3, 4, and 5 only if the subject indicates that she has changed sexual partners or is symptomatic. If the subject 
reports that her partner has been diagnosed or is being treated, she should be assessed/treated as per clinical site standard. 
j. In addition to the urine culture at Screening and Visit 5, subjects will be instructed to contact the clinical site to schedule a dipstick urinalysis and possibly a urine culture 
any time they suspect they may have a UTI. 
k. If dipstick urinalysis is 1+ for analytes of blood, leukocyte esterase, protein or nitrites, the urine should be sent for urine culture and microscopic urinalysis.  
l. Only to be performed if the subject presents to the clinical site with urinary symptoms. Dipstick urinalysis should be performed at any visit where a subject presents to the        
center with urinary symptoms.  
m. A urine pregnancy test should be administered any time a subject misses her period or suspects pregnancy. If a subject reports a positive home pregnancy test, a serum 
β-hCG should be performed.  
n. Subjects will record in their eDiary dates/times of gel use, dates/times of sexual activity, vaginal bleeding, and use of back-up contraception (including reasons for back-up 
contraception, if applicable). Additionally, subjects will record gel-related genitourinary side effects (vaginal itching, burning, or pain) and assess them as mild, moderate, or 
severe; these side effects and non-menstrual cycle vaginal spotting/bleeding will be analyzed as AEs. At each visit, Amphora and eDiary compliance data will be reviewed 
and subjects assessed for re-education. Between visits, sites and subjects will receive alerts if a subject has missed eDiary entries. Sites will record documentation of contact 
with the subject around eDiary compliance. 
o. Provide instructions on how to use the study drug at Enrollment Visit. 
p. Between-visit telephone contact is to include assessment of AEs, concomitant medications, sexual activity, use of backup contraception, compliance with use of the study 
drug and eDiary, need for an unscheduled visit, and confirmation of contact information. 
q. Includes confirmation of subject contact information. At the Enrollment Visit and each subsequent study visit/contact, the subject should be reminded to not have 
intercourse, use the study drug, or place anything in the vagina within 24 hours of the next scheduled visit to the clinical site. 
r. Perform Enrollment Visit upon verification that all eligibility criteria have been met. 
s. At Visit 4, the clinical site staff is to discuss post-treatment contraception with the subject, which would be started at completion of Cycle 7. 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 13 of 39 
 
Figure 1: Study Visit Timing Based on Menstrual Cycle at Enrollment 
 
V=clinical site visit 
Visit 5/Exit visit is to take place 14-30 days after the seventh study cycle or from last use of study product for early termination (unless being followed for 
pregnancy) 
Telephone Visit is to take place between V3 and V4 
Notes: Duration of Cycle 0 is number of days from enrollment to start of first on-study menstrual period. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 14 of 39 
 
4 STATISTICAL METHODS 
4.1 Data Quality Assurance 
All tables, figures, and data listings to be included in the report will be independently checked for 
consistency, integrity and in accordance with standard Health Decisions procedures. 
4.2 General Presentation Considerations 
This section details general policies to be used for the statistical analyses. Deviations from these 
general policies may be given in the specific detailed sections of this statistical analysis plan. 
When this situation occurs, the rules set forth in the specific section take precedence over the 
general policies. The following policies will be applied to all data presentations and analyses: 
• 
All statistical tests will use a 2-sided significance level of a = 0.05. 
• 
Summary statistics will consist of the number and percentage of responses in each 
category for discrete variables, and N, mean, median, standard deviation (SD), 
minimum, and maximum for continuous variables. 
• 
All mean and median values will be formatted to one more decimal place than the 
measured value. SD will be formatted to two more decimal places than the 
measured value. 
• 
All percentages will be rounded to one decimal place. The number and percentage of 
responses will be presented in the form XX (XX.X), where the percentage is in the 
parentheses. The decimal of the percentage may be dropped due to space constraints 
when creating a table. The denominator for percentage calculations will be the number 
of non-missing observations. 
• 
All listings will be sorted for presentation in order of site number, subject number, 
and date of procedure or event. 
• 
When necessary for analysis purposes, partial dates will be completed (i.e., turned 
into complete dates) using the most conservative approach. 
• 
All analysis and summary tables will have the population sample size in the 
column heading. 
• 
Baseline is defined as the last non-missing measurement taken on (prior to treatment) or 
before enrollment. 
• 
Calculating change from baseline to a visit will be done as follows: Change = Visit 
- Baseline 
• 
Version 9.4 of SAS or higher will be the statistical software package used to produce 
all summaries, listings, statistical analyses, and graphs. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 15 of 39 
 
4.3 Analysis Populations 
Intent-To-Treat (ITT): all subjects enrolled into the study. 
Safety Population: ITT subjects who use at least one application of the study product. 
Modified Intent-To-Treat (MITT): Subjects must meet requirements 1, 2, and 3 simultaneously 
and at least one of 4 or 5 to be included in MITT: 
1. between 18 to 35 years of age (inclusive) at enrollment 
2. at least one report of pregnancy after being enrolled (subjects with a positive serum 
pregnancy test at enrollment will not be included in the MITT population). 
3. ITT subjects whose diaries indicate they had at least one episode of coitus while using 
the assigned study product (also referred as "Typical-Use") 
4. have at least 1 cycle without any backup contraception or emergency contraception 
(EC) recorded in the eDiary product use questionnaire 
5. became pregnant and the pregnancy had a conception date that occurred after enrollment and 
within 7 days of the date of last dose of study product. 
Efficacy Evaluable (EE): a subset of the MITT population that includes only those subjects 
whose diaries indicate that they used the study product correctly for every intercourse for at least 
one menstrual cycle (also referred as “Perfect-Use” or “Per Protocol”). Cycles in which the study 
product was used incorrectly for one or more coital acts will be removed, and the correct use 
cycles will be compressed to provide contiguous cycles of correct use. 
The Table 2 provides the handling rules of the analysis populations for special situations. 
Table 2: Handling Rules of the Analysis Populations for Special Situations 
Situation 
Rule for ITT  
Population 
Rule for all Other 
Populations 
Screen failures 
Excluded 
Excluded 
Not receiving treatment 
Included 
Excluded 
Subject enrolled into the study more 
than once 
Only include first 
enrollment 
Only include first 
enrollment 
Subject enrolled in another 
interventional contraceptive study 
Included 
Excluded 
 
Screen failures and the 2nd enrollment for a subject will be excluded from all tables and listings 
except for the data listing which is specifically designed to list these subjects. However, 
rescreening will be allowed for this study. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 16 of 39 
 
4.4 Study Subjects 
4.4.1 
Disposition of Subjects 
Subject disposition will be summarized for the ITT population. The following data will be 
presented: 
• The number and percentage of subjects who completed or discontinued prematurely 
from the study. The number and percentage of subjects who discontinued for each reason 
will be presented. Data will be summarized for all subjects. 
• A listing of subjects that discontinued prematurely from the study. The listing will 
include information about study center, subject number, age, date of enrollment, last 
study product use date, number of cycles completed, and reason for discontinuation. 
• The number and percentage of all subjects at each scheduled visit. 
• The number of subjects who were enrolled at each study center and the number 
and percentage of subjects who completed or discontinued at each study center 
will be summarized for all subjects. 
The End of Study eCRF will be used to determine who discontinued prematurely from the 
study. 
4.4.2 
Study Protocol Deviations 
The number and percentage of subjects with each violation from protocol inclusion and 
exclusion criteria will be summarized for all subjects in the ITT population.  
4.5 Demographic and Pre-Treatment Characteristics 
4.5.1 
Demographic 
Subject demographics will be summarized for the ITT, Safety Population, MITT, and EE 
populations. The summary of demographics will include age, race, ethnicity, height (in), and 
weight (lb) at baseline, and body mass index (kg/m2). 
A sensitivity analysis will also be performed for the ITT population to detect the differences 
between completers and non-completers with respect to the following characteristics: age, 
race, ethnicity, and body mass index (kg/m2).   
4.5.2 
Gynecological History 
The following gynecological history data will be summarized for ITT population: 
• The number and percentages of subjects with urinary tract infection (UTI) history 
(never, not in the past year, once in the past year, twice in the past year, more than twice 
in the past year, don’t know/uncertain); 
• The number and percentages of subjects with yeast infection history (never, not in the 
past year, once in the past year, twice in the past year, more than twice in the past year, 
don’t know/uncertain); 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 17 of 39 
 
• The number and percentages of subjects with bacterial vaginosis history (never, not in the 
past year, once in the past year, twice in the past year, more than twice in the past year, 
don’t know/uncertain); 
• Summary statistics (sample size, mean, median, SD, minimum, and maximum) 
for age at menarche; 
• Summary statistics (sample size, mean, median, SD, minimum, and maximum) 
for typical length of menstrual cycle length (in days); 
• Summary statistics (sample size, mean, median, SD, minimum, and maximum) 
for typical duration of menses (in days). 
4.5.3 
Contraception Use History 
The number and percentage of current users, recent users (used within last 6 months), prior 
users (used greater than 6 months ago), and never users of the following contraceptive 
methods reported within the past 1 year from the time of screening will be summarized: 
male condom, female condom, diaphragm/cervical cap/sponge, oral contraceptive, 
spermicide, vaginal ring, contraceptive patch, rhythm method (fertility awareness), 
withdrawal method, progestin or non-hormonal intrauterine device (IUD), injectable 
contraceptive, contraceptive implant), abstinence, emergency contraception, and other.   
This summary will be conducted on the ITT population. 
4.5.4 
Obstetric History 
Number of pregnancies, number of full-term liveborn deliveries, number of preterm liveborn 
deliveries, number of living children, number of stillbirth/intrauterine demise > 20 weeks 
deliveries, number of ectopic pregnancies, number of spontaneous abortions, and number of 
elective abortions will be summarized descriptively. This summary will be conducted on the 
ITT population. 
4.5.5 
Medical History 
 
Medical history will be coded using MedDRA. The number and percentage of subjects reporting 
each medical condition will be summarized by body system and preferred term for the ITT 
population.  The number and percentage of subjects reporting any medical history will also be 
reported. 
 
If subject reports the same medical condition more than once, then that subject is only counted 
once for the summary of that medical condition. 
 
All medical history will be coded with MedDRA 21.0. 
4.5.6 
Pre-Treatment Signs and Symptoms 
 
Pre-treatment signs and symptoms will be coded using MedDRA. The number and percentage of 
subjects reporting each pre-treatment sign and symptom will be summarized by body system and 
preferred term for the Safety population.  The number and percentage of subjects reporting any 
pre-treatment signs and symptoms will also be reported. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 18 of 39 
 
 
If subject reports the same pre-treatment sign or symptom more than once, then that subject is 
only counted once for the summary of that pre-treatment sign or symptom. 
 
All pre-treatment signs and symptoms will be coded with MedDRA 21.0. 
4.5.7 
Prior and Concomitant Medications 
Summaries for prior and concomitant medications will be done for the Safety Population. The 
following summaries will be performed: 
• Prior Medications – Prior medications are considered to be any medication that 
was stopped prior to the date of enrollment. 
• Concomitant Medications – Concomitant medications are considered to be 
any medication that was taken on or after the date of enrollment. 
All medications will be coded to the therapeutic drug classes and generic drug names using the 
World Health Organization (WHO) Drug classifications. The WHO Drug dictionary version 
used for this study will be March 2018. 
Each summary will give the number and percentage of subjects who took medications that were 
coded to each generic drug name and therapeutic drug class, as well as the number and 
percentage of subjects that took any medication at all. 
4.6 Treatment Compliance and Study Instruction Departures 
Treatment compliance in the Safety Population will be calculated using 5 indices. These 
5 indices are the proportion of following acts among all acts of intercourse: 
A. study product only and was used as directed 
B. study product only but product not used as directed 
C. study product and other birth control were used 
D. other birth control only was used 
E. no study drug or birth control was used (i.e. unprotected intercourse) 
F.  
For individual subjects, each index will be calculated as: 
 
 
 
Total number of acts of intercourse for this index in all cycles 
 
 
 
Total number of acts of intercourse in all cycles 
 
Descriptive statistics will be presented for each index. 
Based on the index value, each subject will be in one, and only one, of the following categories 
for study method only and proper use: 
X 100 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 19 of 39 
 
• 0% - 49% 
• 50% - 69% 
• 70% - 89% 
• > = 90% 
Based on the index value, each subject will be in one, and only one, of the following categories 
for study product only but product not used as directed, study product and other birth control, 
other birth control only, and no birth control was used: 
 
• 0% - 9% 
• 10% - 19% 
• 
20% - 29% 
• 
30% - 39% 
• 
40% - 49% 
• >50% 
 
The number and percentage of subjects in each of the above categories will be presented for all 
subjects. 
Various departures from study instructions are as follows: 
•  Intercourse occurred more than 1 hour but less than or equal to 1.5 hours after 
application 
•  Intercourse occurred more than 1.5 hours but less than or equal to 2 hours after 
application  
•  Intercourse occurred more than 2 hours but less than or equal to 2.5 hours after 
application  
•  Intercourse occurred more than 2.5 hours after application  
The departures from study instructions summary will include the number and percent of subjects 
who report at least one departure from study instructions. The table will also summarize the 
percentage of acts with departure and categorize them in the following categories: 
• 0% - 5% 
• 6% - 10% 
• 11% - 25% 
• 26% - 49% 
• ≥ 50% 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 20 of 39 
 
4.7 Efficacy Evaluation 
Typical-use 7-cycle pregnancy analyses will be done for the MITT populations, and perfect-use 
7-cycle pregnancy analyses will be done for the EE population. 
4.7.1 
Analysis and Data Conventions 
4.7.1.1 Definition of Baseline 
Baseline is defined as the last non-missing measurement on (prior to treatment) or before 
enrollment. 
4.7.1.2 Definition of Cycle 
 
The cycle number will be derived from the eCRF menses start dates as follows: 
Cycle 0 = date of enrollment through date before 1st menses started after enrollment (Note: 
this cycle includes cases where menses started on the day of enrollment) 
Cycle 1 = date 1st menses started after enrollment through date before 2nd menses started after 
enrollment 
Cycle 2 = date 2nd menses started after enrollment through date before 3rd menses started after 
enrollment 
Cycle 3 = date 3rd menses started after enrollment through date before 4th menses started after 
enrollment 
Cycle 4 = date 4th menses started after enrollment through date before 5th menses started after 
enrollment 
Cycle 5 = date 5th menses started after enrollment through date before 6th menses started after 
enrollment 
Cycle 6 = date 6th menses started after enrollment through date before 7th menses started after 
enrollment 
Cycle 7 = date 7th menses started after enrollment through date before 8th menses started after 
enrollment 
Cycle 8 = date 8th menses started after enrollment through date before 9th menses started after 
enrollment 
If the subject became pregnant and the pregnancy adjudication committee estimated the date of 
conception, but the subject has no diary for the cycle that contains the estimated date of 
conception, then the pregnancy will be assigned to day 14 of the cycle.  If partial start/end dates 
occur, then it will be assumed that the cycles were equal length to determine the imputed start/end 
dates of the cycle.  If estimated date of conception could not be provided by the pregnancy 
adjudication committee due to insufficient information, then pregnancy will be assigned day 14 of 
the first potentially evaluable cycle after enrollment unless there is documentation to show the 
pregnancy occurred in a later cycle. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 21 of 39 
 
4.7.1.3 Multiple Comparisons/Multiplicity 
This study has only one primary endpoint, no multiplicity adjustment is necessary.  
4.7.1.4 Interim Analyses 
No formal statistical interim analyses for efficacy are planned for this study. 
4.7.2 
Primary Efficacy Analysis 
The primary efficacy endpoint is the cumulative percentage of typical-use 7-cycle pregnancy. 
The primary hypothesis to be tested is whether subjects using Amphora vaginal gel have a 7-
cycle cumulative pregnancy percentage less than or equal to 21%, that is, 
 
 
 
 
 
 
HO:  πA   >   21 %   vs.   HA:   πA    < 21 % 
where 𝜋𝜋𝐴𝐴 represents the 7-cycle cumulative pregnancy percentage for Amphora. The Kaplan-  
Meier (KM) estimate and its 95% CI (based on Greenwood’s method) of the 7-cycle cumulative  
pregnancy percentage of women in the MITT population will be calculated. If the upper bound of 
the 95% CI is ≤ 21%, then the null hypothesis will be rejected and the conclusion will be that the 
7-cycle cumulative pregnancy percentage is ≤ 21%. 
4.7.2.1 Derivation of the Primary Endpoint 
a. The primary variable is the number of cycles from enrollment to the first pregnancy 
within seven cycles, which will be derived in the following steps: 
•  Determining the evaluable cycles: Cycles must meet all conditions given below to 
be considered evaluable cycles: 
o Cycles 0-6 for subjects who are enrolled for at least 21 days prior to the start 
of her next menses (includes subjects who start menses on the day of 
enrollment), or Cycles 1-7 for subjects who are enrolled in less than 21 days 
prior to the start of her next menses; 
o Cycles that are indicated by the eDiary product use questionnaire that no 
backup contraception or EC are used or in which subjects become pregnant; 
o Cycles with length within the range of 21 days to 35 days or in which subjects 
have an on-treatment pregnancy. 
o Cycles where at least one entry of diary is recorded or in which subjects are 
pregnant. 
o Cycles must have at least one act of intercourse. 
o Cycles must start on or before date of last study product use + 7 days 
o For EE analyses, cycles in which the eDiaries indicate that study drug 
was used correctly for every act of intercourse during that cycle. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 22 of 39 
 
• 
Compressing the evaluable cycles: Evaluable cycles will be compressed to form 
contiguous evaluable cycles for each subject sequentially. 
• 
Determining the date of conception: 
o The Pregnancy Review Committee will review all confirmed pregnancies 
except for subjects who had a borderline or positive b-hCG serum at 
enrollment, and this information will be provided to data management in an 
Excel file from the VCAS database.  The committee will determine if the 
pregnancy occurred on-treatment (defined as date of conception between 
enrollment to <8 days after final study product use) or not on‑treatment 
(defined as date of conception prior to enrollment or after 7 days following 
final study product use), or whether there is insufficient information for 
adjudication.  The Pregnancy Review Committee assessment of pregnancies 
being on-treatment or not will be used for the primary endpoint.  Pregnancies 
that could not be adjudicated due to insufficient information will be treated as 
on-treatment.  The medical monitor will review the VCAS file and if the 
committee provided their own estimated date of conception in the “If 
disagree, provide rationale” field then the medical monitor will create a new 
column in the VCAS excel file and will enter into the new column the 
estimated date of conception provided by the adjudication committee in the 
“If disagree, provide rationale” field.  This re-entry of the estimated date of 
conception will enable the programming of the statistical analysis.   
For confirmed pregnancies, the date of conception will be assessed from the 
following: 
• First trimester transvaginal ultrasound (considered the most 
accurate; later ultrasounds will not be used for redating) 
• Estimate based on pelvic and/or abdominal examination or 
pregnancy outcome 
• eDiary information (e.g., last menstrual period and sexual activity) 
• Quantitative β-hCG determination 
• Urine hCG (date of last negative and first positive) 
• Investigator estimation in the absence of above criteria 
• Determining of censoring for cycles to pregnancy: Subjects will be censored from 
analysis at the earliest of: 
o The estimated date of conception that occurred between enrollment and 
<8 days after final study drug use 
o  Date of last study product use + 7 days 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 23 of 39 
 
o The conclusion of her seventh cycle on-treatment + 7 days (up to a total of 
252 days [or 301 days for the sensitivity analysis, allowing a cycle length 
range of 21 to 42 days])  
4.7.3 
Secondary Efficacy Analyses 
 
4.7.3.1 Sensitivity Analysis with Respect to the Cycle Range 
The primary analysis will be repeated with the cycle length expanded from 21 – 35 days to 21 – 
42 days. 
4.7.3.2 Sensitivity Analysis with Respect to the Dosing Time with Respect to Sexual 
Intercourse 
To evaluate the effect of the dosing time with respect to the time of sexual intercourse, the 
number and percentage of intercourse acts in the following categories will be shown: 
• The number of intercourse acts where dosing time <= 1 hour before intercourse 
• The number of intercourse acts where dosing time > 1.5 hours but <= 2 hours before 
intercourse 
• The number of intercourse acts where dosing time > 2 hours but <= 2.5 hours before 
intercourse 
• The number of intercourse acts where dosing time > 2.5 hours before intercourse 
 
The number and percentage of subjects in the following categories will also be shown: 
• The number of pregnancies that occurred in a cycle where the longest duration from 
dosing time to intercourse was <= 1 hour 
• The number of pregnancies that occurred in a cycle where the longest duration from 
dosing time to intercourse was > 1 hour but <= 1.5 hours 
• The number of pregnancies that occurred in a cycle where the longest duration from 
dosing time to intercourse was >1.5 hours but <=2 hours 
• The number of pregnancies that occurred in a cycle where the longest duration from 
dosing time to intercourse was >2 hours but <=2.5 hours 
• The number of pregnancies that occurred in a cycle where the longest duration from 
dosing time to intercourse was >2.5 hours 
4.7.3.3 Perfect-Use 7-Cycle Pregnancy Probabilities 
As a secondary evaluation of contraceptive efficacy, the 7-cycle cumulative pregnancy 
percentage of women in the EE population will be estimated by KM method. Each woman in the 
EE population is evaluated for efficacy for menstrual cycles when she has used the study product 
consistently and correctly as reflected in her diary recordings. Non-perfect-use and non-
evaluable cycles will be removed from the analysis. The perfect-use analysis will use the same 
conventions and analysis rules mentioned for the typical-use analysis, except that non-perfect 
cycles with a pregnancy will not be included. Greenwood’s method for calculating variance will 
be used to construct 95% confidence intervals. 
4.7.3.4 Pearl Rates from 7-Cycle Data 
The Pearl rate, also called the Pearl index (Higgins 1985), is defined as the number of 
pregnancies in 100 woman-years of method use.  


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 24 of 39 
 
Because this study will use natural women cycles and the days will vary from woman to 
woman, the primary method of analysis will be: 
 
 
 
   Number of pregnancies * 365.25 * 100  
 
 
          Total number of days exposed 
 
For comparison, the Pearl rate will also be calculated using a 28-day cycle: 
  
Number of pregnancies * 13 * 100 
 
 
 
     Total number of menstrual cycles 
Both cycle-based and year based Pearl rates and their two-sided 95% CI will be presented, 
assuming a Poisson distribution.  The Pearl rate will be done for the MITT and EE 
populations. 
4.7.3.5 Summary of Number of Diary Cycles and Cycles Excluded from EE Population 
The average number of diary cycles will be summarized for all MITT subjects through seven 
cycles. Diaries where backup contraception or EC were used will be excluded unless the 
subject became pregnant in that cycle. The number of cycles with incorrect use of study 
product which result in exclusion from the EE analysis will be calculated for each subject and 
summarized descriptively. 
 
4.8 Safety Evaluation 
All safety analyses will be done for the Safety Population. 
All laboratory data will be presented in the conventional United States (US) units. 
Final evaluation is defined to be the last evaluation performed after the date of enrollment. 
4.8.1 
Treatment Exposure 
Treatment exposure will be summarized for the Safety Population. Treatment exposure will be 
summarized by the number of times the treatments are used in acts of intercourse, the length of 
time over which the treatments are used, the number of times study product was used per cycle, 
and the number of cycles in the study. The number of times the treatments are used in acts of 
intercourse will be calculated as the sum of total number of intercourse acts where study product 
used as directed, total number of intercourse acts where study product not used as directed, and 
total number of intercourse acts with study product and other birth control. The length of time 
will be calculated as: last date study product was used – date of enrollment + 1. The number of 
cycles in the study will be the highest numbered cycle  that started on or before the date of last 
study product use + 1 (the +1 is to account for cycle 0 (subjects are randomized mid cycle and 
that cycle is cycle 0)). 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 25 of 39 
 
4.8.2 
Adverse Events 
Incidence of adverse events will be summarized by SOC and PT. The number and percentage of 
subjects with each SOC and PT will be presented. Tables to summarize the incidence rates will 
be created for each of the following groups: 
• Adverse events 
• Serious adverse events 
• Adverse events leading to premature discontinuation 
• Adverse events by intensity 
• Adverse events by relationship to study drug 
• Adverse events by intensity and relationship to study drug (summary will present 
number of adverse events reported, not number of subjects) 
• Adverse events presented in descending order of frequency by PT (no SOC shown) 
If subject reports the same adverse event more than once, then that subject is only counted once 
for the summary of that adverse event, using the most severe intensity. The only exception to this 
will be for the summary by relationship to study drug. For that summary, if subject reports the 
same adverse event more than once, then that subject is only counted once for the summary of 
that adverse event, using the most severe relationship to study drug. The same principle will be 
applied at the body system level summary. 
If intensity to study drug is reported as unknown, then the adverse event will be summarized as 
severe.  If relationship to study drug is reported as unknown, then the adverse event will be 
summarized as certain/definite. 
Adverse events that led to premature discontinuation from the study will be listed. Serious 
adverse events will also be listed. These listings will contain details about the adverse event such 
as intensity and relationship to study drug. Other supportive data, such as the subject’s age, will 
be given. 
A sensitivity analysis will also be performed for the Safety population to detect the 
differences between completers and non-completers with respect to adverse events.   
All adverse events will be coded with MedDRA 21.0. 
4.8.3 
Genitourinary Side Effects 
Genitourinary side effects will include vaginal discharge, vaginal burning, vaginal itching, 
vaginal pain, and other vaginal symptoms as reported by the subject in her eDiary. Partner 
side effects (burning, itching, pain, and other side effects) will also be captured in eDiary. 
Number and percentage of subjects with genitourinary side effects and partner side effects 
will be summarized in the following stratifications: 
• By the time of symptom onset after product application 
o < 5 minutes 
o 5 – 30 minutes 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 26 of 39 
 
o 31 - 60 minutes 
o > 1 hour 
• By the severity of the symptom 
o Mild 
o Moderate 
o Severe 
• By duration of the symptom 
o < 5 minutes 
o 5 – 30 minutes 
o 31 – 60 minutes 
o > 1 hour 
4.8.4 
Gynecological Infections 
The number and percentage of subjects responding to the question “Subject has a Vaginitis?” will 
be presented for the Safety Population by visit..  The following types of vaginitis will also be 
summarized by visit for subjects responding Yes or No for Vaginitis: 
• Yeast/Monilia 
• Bacterial VaginosisTrichomoniasis 
• Other 
Unscheduled visits will be grouped with associated visit (e.g., visit 3.1 will be included with visit 
3).  
4.8.5 
Dipstick Urinalysis and Urine Culture 
Dipstick urinalysis analytes include blood (negative, trace, 1+, 2+, 3+), leukocyte esterase 
(negative, trace, 1+, 2+, 3+), protein (negative, trace, 1+), and nitrites (negative, trace, 1+, 2+, 
3+,4+).  Number and percent of subjects for each category will be presented by visit and final 
evaluation. 
For urine culture and UTI results, number and percent of subjects will be presented for the Safety 
Population by visit and final evaluation. Urine culture result categories are as follows: ≥100,000 
CFU/ml, <100,000 CFU/ml, indeterminate and negative.  UTI result categories are as follows: 
Yes – a  symptomatic UTI: compliant of urinary symptoms and 1+ for analytes of blood, 
leukocyte esterase, protein or nitrites and a minimum bacterial count of 10,000 colony forming 
units (CFU)/mL with the presence of uropathogen; Yes – a symptomatic UTI: presence of 
symptoms and > 100,000 CFU/mL presence of uropathogen without a positive leukocyte esterase 
by dipstick; Yes – an asymptomatic UTI : absence of symptoms and a bacterial count of > 
100,000 CFU/mL with the presence of uropathogen; No – not per protocol definitions.  
Wet mount assessment results are classified as normal or abnormal.  The number and percentage 
of subjects with improved (changed from abnormal in baseline to normal), no change, and 
worsened (changed from normal in baseline to abnormal) results will be presented for each visit 
and final evaluation.  Number and percent of subjects in each sub-category of abnormal wet 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 27 of 39 
 
mount (including WBC, trichomonas, hyphae/spores, clue cells (>20%)) will also be presented.  
Vaginal pH will also be summarized for each visit and final evaluation. 
Unscheduled visits will be grouped with the associated visit (e.g., visit 3.1 will be included with visit 3). 
4.8.6 
Gynecological Examination 
For gynecological examinations, each body system will be categorized as normal or abnormal. 
Gynecological examination changes from baseline will be categorized as improved, no change, or 
worsened for each body system.  The number and percentage of subjects in each category of 
change will be given at each visit and final evaluation and body system.  
An adaptation of the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and 
Pediatric Adverse Events, Version 2.0, Addendum 1 – Female Genital Grading Table for Use in 
Microbicide Studies will be used by the investigator to grade changes from baseline in vulvar, 
vaginal or cervical findings noted during the gynecologic exam and determine if they are 
considered significant, as defined as at least one grade increase from baseline (see appendix 
5.1).  
Vulvar, vaginal, and cervical findings will be summarized by visit and final evaluation.  The 
number and percentage of subjects and events for each grade will be presented. 
Unscheduled visits will be grouped with the associated visit (e.g., visit 3.1 will be included with visit 3).  
4.8.7 
Sexually Transmitted Infection Tests 
Sexually transmitted infections (STI) tests for chlamydia and gonorrhea will be classified as 
positive or negative. The number and percentage of subjects in each test result will be presented 
by visit. Unscheduled visits will be grouped with the associated visit (e.g., visit 3.1 will be included 
with visit 3). 
4.8.8 
Clinical Laboratory Evaluation 
CBC and chemistry and their change from baseline to final evaluation will be summarized. 
A summary of shifts from baseline to final evaluation will be given for each parameter. The 
normal range for each parameter will be used to create categories of low, normal, or high. Any 
result that is higher (lower) than the upper (lower) limit of normal will be categorized as high 
(low) and any result within the lower and upper limits of normal will be categorized as normal. 
CBC and chemistry data will be located in separate tables. 
4.8.9 
Vital Signs 
Vital signs and weight and their change from baseline will be summarized by visit. Unscheduled 
visits will be grouped with the associated visit (e.g., visit 3.1 will be included with visit 3). 
4.8.10 Pregnancy Outcome 
The pregnancy outcomes will be summarized as follows: 
• The number and percentages for each fetal status category (pre-term birth, full term birth, 
stillbirth, spontaneous termination, induced termination, ectopic pregnancy, unknown). 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 28 of 39 
 
• The number and percentages for sex of fetus (male, female, unknown) 
• The number and percentages for maternal complications 
• Summary statistics (sample size, mean, median, SD, minimum, and maximum) for 
Apgar Scores (1 min and 5 min) 
• Summary statistics (sample size, mean, median, SD, minimum, and maximum) for 
the gestational age (weeks) 
• Summary statistics (sample size, mean, median, SD, minimum, and maximum) for 
the birth weight (pounds) 
4.9 Subject Satisfaction 
All analyses described in this section will be performed on the Safety population. 
4.9.1 
Subject Satisfaction Questionnaires 
Four endpoints will be defined for Subject Satisfaction Questionnaires: 
• Satisfaction level to study product which will be evaluated at baseline and visit 3-5 based 
on the answers to question “how satisfied were you with your most recent/study birth 
control method”: 
a. Very satisfied 
b. Satisfied 
c. Somewhat satisfied 
d. Somewhat dissatisfied 
e. Dissatisfied 
• Likelihood of recommendation as a vaginal contraceptive gel which will be evaluated 
at Visit 3-5 with outcome: 
f. Very likely 
g. Likely 
h. Somewhat likely 
i. Somewhat unlikely 
j. Unlikely 
• Likelihood of recommendation as another birth control option which will be evaluated 
at Visit 3-5 with outcome: 
k. Very likely 
l. Likely 
m. Somewhat likely 
n. Somewhat unlikely 
o. Unlikely 
• Likelihood to continue use which will be evaluated at Visit 3-5 with outcome: 
p. Very likely 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 29 of 39 
 
q. Likely 
r. Somewhat likely 
s. Somewhat unlikely 
t. Unlikely 
All four endpoints will be summarized using frequency and percentage by visit and outcome 
level. Unscheduled visits will be grouped with the associated visit (e.g., visit 3.1 will be included 
with visit 3).


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 30 of 39 
 
4.9.2 
Sexual Function Questionnaire 
The Sexual Function Questionnaire has 10 variables: 
1. Vaginal dryness during sexual activity 
2. Lack of sexual interest or desire 
3. Vaginal tightness 
4. Pain during penetration or intercourse 
5. Anxiety about your sexual performance 
6. Unable to orgasm 
7. Vaginal bleeding or irritation from penetration or intercourse 
8. Increased sensitivity of your skin to intimate touching 
9. Sharp pain inside or outside your vagina 
10. Other problem with sexuality 
The outcomes and coding for these 10 Variables are provided in Table 3. 
Table 3: Sexual Function Questionnaire Outcomes and Coding 
Subject’s Answer 
Code 
Not at all 
1 
Seldom, less than 25% of the time 
2 
Sometimes, about 50% of the time 
3 
Usually, about 75% of the time 
4 
Always 
5 
The problem stops your sexual activity 
6 
 
All variables given above will be summarized using frequency and percentage by visit and 
outcome categories. Unscheduled visits will be grouped with the associated visit (e.g., visit 3.1 
will be included with visit 3). 
 
4.9.3 
Sexual Satisfaction and Lubrication 
Sexual Satisfaction and Lubrication will be assessed with the following questions, asked 
at baseline and at each subsequent visit: 
• Baseline: What impact did your most recent contraceptive method have on your sex life 
in the last 4 weeks of use? 
• Visit 3-5: What impact has the study contraceptive method had on your sex life since 
your last study visit? 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 31 of 39 
 
The response set for these questions is as follows:  
a. My sex life was a lot better than before 
b. My sex life was a little better than before 
c. My sex life was no different than before 
d. My sex life was a little worse than before 
e. My sex life was a lot worse than before 
The Female Sexual Function Index (FSFI), a 19-item questionnaire, provides scores on six 
domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain) as well as 
a total score. Only question 10 from the FSFI will be summarized according to the following 
response set: 
• 
10. Over the past 4 weeks, how difficult was it to maintain your lubrication ("wetness") 
until completion of sexual activity or intercourse? 
u. No sexual activity 
f. Extremely difficult or impossible 
g. Very difficult 
h. Difficult 
i. Slightly difficult 
j. Not difficult 
All variables given above will be summarized using frequency and percentage by visit and 
outcome categories. Unscheduled visits will be grouped with the associated visit (e.g., visit 3.1 
will be included with visit 3). 
4.10 Missing Data Handling 
4.10.1 Imputing partial AE and prior/concomitant medication start dates 
a) If the year is unknown, the date will not be imputed if the stop date of the event is earlier  
than the first dose time; otherwise, it will be imputed as the year of the first dose time. 
b) If the month is unknown, then: 
11. If the year matches the first dose date, then impute to the month and day of 
the first dose date. 
12. Otherwise, assign ‘January’. 
c) If the day is unknown, then: 
13. If the month and year match the first dose date, then impute to the day of the 
first dose date. 
14. Otherwise, assign ‘01’. 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 32 of 39 
 
 
4.10.2 Imputing partial AE and prior/concomitant medication stop dates 
a) If the year is unknown, the date will not be imputed if the start time of the event is 
after the last dose time, otherwise it will be imputed as the year of the last dose time. 
b) If the month is unknown, then assign ‘December’. 
c)  If the day is unknown, then impute to the last day of the month.  
4.11 Pregnancy Intendedness 
The pregnancy intendedness scale and its change from the baseline will be summarized 
descriptively by visit. Unscheduled visits will be grouped with the associated visit (e.g., visit 
3.1 will be included with visit 3). 
4.11.1 Determination of Sample Size 
Simulation methods are used to evaluate the likelihood of various sample sizes providing enough 
information to test the primary hypothesis (one-sided Type 1 error of 0.025) and enough use 
cycles of Amphora gel to address other regulatory requirements. The six month (183 d) 
cumulative pregnancy percentage was estimated using Kaplan-Meier methods. 
The sample size determination assumes the following: 
• Study drug pregnancy percentage: 16.5% 
• 26.5% of subjects fail to qualify for the primary efficacy analysis population 
• Of the subjects that qualify for the primary efficacy analysis population, the 
average number of evaluable efficacy cycles per subject: 3.17 
• Exponential hazard for: 
o Pregnancy rate first 6 months: 16.5% 
o Drop out month 1: 10% 
o Drop out months 2-6: 38% 
With 1349 participants aged 18 through 35 years (inclusive), the study will have 90% power to 
ensure that the upper limit of the 95% CI of the cumulative seven-cycle pregnancy rate is less 
than or equal to 21%. The expected number of completers is 515 and the expected number of 
cycles evaluable for safety is at least 3143. 
 
 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 33 of 39 
 
5 
Appendix 
 
5.1 Grading for Vulvar, Vaginal, or Cervical Findings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 34 of 39 
 
6 PROPOSED TABLES, FIGURES AND LISTINGS 
 
6.1 Proposed Tables and Figures 
 
Number 
Title 
Population 
14.1.1 
Subject Disposition 
ITT 
14.1.2 
Listing of Subjects that Discontinued Prematurely  
ITT 
14.1.3 
Number of Subjects at Each Visit 
ITT 
14.1.4 
Number of Subjects at Each Study Site 
ITT 
14.1.5 
Summary of Protocol Deviations   
Safety Population 
14.1.6 
Demographics 
ITT 
14.1.6.1 
Demographics for the Safety Population 
Safety Population 
14.1.6.2 
Demographics for the Modified Intent-to-Treat Population 
MITT 
14.1.6.3 
Demographics for the Efficacy Evaluable Population 
EE 
14.1.7 
Sensitivity Analysis to Dropouts with Respect to 
Demography 
ITT 
14.1.8 
Gynecological History 
ITT 
14.1.9 
Contraception Use History 
ITT 
14.1.10 
Obstetric History 
ITT 
14.1.11 
Medical History 
ITT 
14.1.12 
 Pre-Treatment Signs and Symptoms 
ITT  
14.1.13 
Incidence of Prior Medications 
Safety Population 
14.1.14 
Incidence of Concomitant Medications 
Safety Population 
14.1.15 
Summary of Compliance as Determined by Contraceptive 
Method 
Safety Population 
14.1.16 
Percent of Coital Acts as Determined by Contraceptive 
Method 
Safety Population 
14.1.17 
Percent of Coital Acts with Departures from Study 
Instructions 
Safety Population 
14.1.18  
(figure) 
Percentage of Subjects who Completed the Study or 
Prematurely Discontinued 
ITT 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 35 of 39 
 
Number 
Title 
Population 
14.2.1 
Seven-Cycle Cumulative Pregnancy Probabilities for 
Subjects with Typical-Use 
MITT 
14.2.2 
Sensitivity Analysis with Respect to the Cycle Length 
MITT 
14.2.3 
Sensitivity Analysis with Respect to the Dosing Time with 
Respect to Sexual Intercourse 
MITT 
14.2.4 
Seven-Cycle Cumulative Pregnancy Probabilities for 
Subjects with Perfect-Use 
EE 
14.2.5 
Typical-Use Seven-Cycle Based Pearl Rates 
MITT 
14.2.6 
Perfect-Use Seven-Cycle Based Pearl Rates 
 EE 
14.2.7 
Summary of Number of Evaluable Cycles 
MITT 
14.2.8 
Summary of Cycles Excluded from Efficacy Evaluable 
Analysis  
MITT 
14.2.9 
(figure) 
Pregnancy Percentage Curves by Kaplan-Meier Method for
Subjects with Typical Use 
MITT 
14.2.10 
(figure) 
Pregnancy Percentage Curves by Kaplan-Meier Method for
Subjects with Perfect-Use 
EE 
14.3.1.1 
Incidence of Adverse Events 
Safety 
P
l i
14.3.1.2 
Incidence of Serious Adverse Events 
Safety 
l i
14.3.1.3 
Incidence of Adverse Events Leading to Premature 
Discontinuation 
Safety 
Population 
14.3.1.4 
Incidence of Adverse Events by Intensity 
Safety 
l i
14.3.1.5 
Incidence of Adverse Events by Relationship to Treatment 
Safety 
l i
14.3.1.6 
Incidence of Adverse Events by Intensity and Relationship to 
Treatment 
Safety 
Population 
14.3.1.7 
Incidence of Adverse Events by Descending Frequency 
Safety 
P
l i
14.3.1.8 
Sensitivity Analysis to Dropouts with Respect to Adverse 
Events 
Safety 
14.3.2.1 
Listing of Serious Adverse Events 
Safety 
Population 
14.3.2.2 
Listing of Adverse Events that Led to Premature 
Discontinuation 
Safety 
Population 
14.3.5.1 
Treatment Exposure 
Safety 
Population 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 36 of 39 
 
Number 
Title 
Population 
14.3.5.2 
Incidence of Genitourinary Side Effects by the Time of 
Symptom Onset after Product Application 
Safety Population 
14.3.5.3 
Incidence of Genitourinary Side Effects by Severity of the 
Symptom 
Safety Population 
14.3.5.4 
Incidence of Genitourinary Side Effects by Duration of the 
Symptom 
Safety Population 
14.3.5.5 
Incidence of Genitourinary Infections 
Safety Population 
14.3.5.6 
Dipstick Urinalysis and Urine Culture Results 
Safety Population 
14.3.5.7 
Summary of Wet Mount Assessment Results 
Safety Population 
14.3.5.8 
Change in Gynecological Examination Findings 
Safety Population 
14.3.5.9 
Incidence of Vulvar, Vaginal, or Cervical Findings 
Safety Population 
14.3.5.10 
Sexually Transmitted Infection Test Results 
Safety Population 
14.3.5.11 
Mean Change from Baseline to Final Evaluation for 
Hematology Analytes 
Safety Population 
14.3.5.12 
Shift from Baseline to Final Evaluation for Hematology 
Analytes 
Safety Population 
14.3.5.13 
Mean Change from Baseline to Final Evaluation for Clinical 
Chemistry Analytes 
Safety Population 
14.3.5.14 
Shift from Baseline to Final Evaluation for Clinical 
Chemistry Analytes 
Safety Population 
14.3.5.15 
Mean Change from Baseline to Each Visit for Vital Signs 
and Weight 
Safety Population 
14.3.5.16 
Summary of Pregnancy Outcomes 
Safety Population 
14.3.5.17 
Summary of Subject Satisfaction Questionnaires 
 Safety Population 
14.3.5.18 
Summary of Sexual Function Questionnaire 
 Safety Population 
14.3.5.19 
Summary of Sexual Satisfaction and Lubrication 
 Safety Population 
14.3.5.20 
Summary of Pregnancy Intendedness 
MITT 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 37 of 39 
 
6.2 Proposed Data Listings 
 
Number 
Title 
Population 
16.2.1.1 
Analysis Population 
ITT 
16.2.1.2 
Subject Disposition 
ITT 
16.2.1.4 
End of Trial 
ITT 
16.2.2.1 
Protocol Deviations 
ITT 
16.2.3.1 
Subjects Excluded from MITT or EE Population 
ITT 
16.2.3.2 
Screen Failures and Second Enrollments 
ITT 
16.2.4.1 
Demographics 
ITT 
16.2.4.2 
Medical History 
ITT 
16.2.4.3 
Gynecological History 
ITT 
16.2.4.4 
Contraceptive History 
ITT 
16.2.4.5 
Pregnancy History 
ITT 
16.2.4.6 
Prior and Concomitant Medications 
ITT 
16.2.4.7 
Pre-Treatment Signs and Symptoms 
ITT 
16.2.5.1 
Product Use Diary 
ITT 
16.2.5.2 
Nightly Diary 
ITT 
16.2.5.3 
Follow-up Diary 
ITT 
16.2.6.1 
Menses Data 
ITT 
16.2.6.2 
Pregnancy Test Results 
ITT 
16.2.6.3 
Pregnancy Notification 
ITT 
16.2.6.4 
Pregnancy Outcomes 
ITT 
16.2.6.5 
Ultrasound Report 
ITT 
16.2.7.1 
Adverse Events 
ITT 
16.2.8.1 
Dipstick and Urine Culture Assessments 
ITT 
16.2.8.2 
Laboratory Assessments: STI Tests 
ITT 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 38 of 39 
 
 
Number 
Title 
Population 
16.2.8.3 
Bacterial Vaginosis and Yeast Assessments 
ITT 
16.2.8.4 
Hematology Tests 
ITT 
16.2.8.5 
Clinical Chemistry Tests 
ITT 
16.2.9.1 
Gynecological Exam 
ITT 
16.2.9.2 
Vital Signs 
ITT 
16.2.9.3 
Physical Exam 
ITT 
16.3.1 
Subject Satisfaction Questionnaires 
ITT 
16.3.2 
Sexual Function Questionnaire 
ITT 
16.3.3 
Sexual Satisfaction and Lubrication 
ITT 
16.4.1 
Pregnancy Intendedness 
ITT 
 


AMPHORA®                                                                                                          Statistical Analysis Plan: AMP002 
Evofem, Inc.                                                                                                           Version 5 – 24 October 2018 
 
CONFIDENTIAL AND PROPRIETARY  
 
Page 39 of 39 
 
7 REFERENCES 
 
Higgens J.E., Wilkens L.R. (1985) Statistical comparison of Pearl rates. Am J Obstet Gynecol 
1985; 151:656-9.