Clinical trial NCT01306331: Study of Contraceptive Efficacy & Safety of Phexxi™ (Previously Known as Amphora) Gel Compared to Conceptrol Vaginal Gel
Official title: A Multicenter, Open-Label, Randomized Study of the Contraceptive Efficacy and Safety of Phexxi™ (Previously Known as Amphora) Gel Compared to Conceptrol Vaginal Gel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Contraception
Lead sponsor: Evofem Inc.
Sponsor class: INDUSTRY
Collaborators: name: Health Decisions
First posted: 2011-03-01
Enrollment: 3389
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a research study of a new experimental vaginal gel that helps in vaginal pH regulation and results in immobilization of spermatozoa by maintaining the normally low vaginal pH, even in the presence of semen. This vaginal gel is called Phexxi™ (previously known as Amphora) and was compared to a commercially available spermicide called Conceptrol®, which contains nonoxynol 9; commonly abbreviated as N-9. Conceptrol® can help prevent pregnancy. This study objective was to determine if this product prevents pregnancy when inserted into the vagina before intercourse.

Detailed description: Clinical Trial Design

This is a multicenter, open-label, randomized, controlled, Phase III study of repeated use of Amphora™ gel compared to Conceptrol® Vaginal Gel as the method of contraception over seven cycles of use. In addition, there is an opportunity for Amphora™ gel subjects to continue with study treatment for up to 13 cycles of treatment upon completion of the first seven cycles of treatment.

A subset of subjects (Amphora™ gel and Conceptrol® Vaginal Gel) will undergo colposcopy at the Admission Visit and at the visits after Cycles 1, 3, and 7 (Treatment Exit). Subjects participating for 13 cycles will also undergo colposcopy after Cycles 10 and 13. Colposcopic photographs will be taken at all visits independent of presence of any suspicious areas. Any suspicious areas and clinical findings will be recorded on the colposcopy case report form. The colposcopy evaluator for the subset will be blinded regarding the treatment group of the subject. If at any time during the study the investigator deems colposcopy necessary, colposcopy will be performed on any subject and will not be limited to subjects in the colposcopy subset.

A subset of subjects (Amphora™ gel and Conceptrol® Vaginal Gel) will also have semi-quantitative cultures for E. coli and clinical yeast performed at the Admission Visit and after Cycles 1, 3, and 7 (Treatment Exit) Visits. Subjects participating for 13 cycles will also undergo the assessments after Cycles 10 and 13. Another subgroup will have quantitative vaginal cultures performed after Cycles 1 and 7 (Treatment Exit) Visits, and also after Cycle 13 for subjects participating in the extension.

Selected research centers will also recruit subjects into the subset of women 36-45 years of age at enrollment.

Eligibility criteria: Inclusion Criteria:

* Be healthy women, who are sexually active, at risk for pregnancy, and desiring contraception.
* Be within the age range of 18 through 35 (inclusive) at enrollment if not in the subset of women with an age of 36-45 at enrollment (age subset at select sites).
* Be at low-risk for both human immunodeficiency virus (HIV) and sexually transmitted disease (STD) infection and currently have a single sex partner (≥ 4 months) who is also at low-risk for both HIV and STD infection.
* Have a negative urine pregnancy test prior to enrollment.
* Have normal cyclic menses with a usual length of 21 to 40 days over the last two cycles or at least one spontaneous, normal menstrual cycle (two menses) since delivery, abortion, or after discontinuing hormonal contraception/hormonal therapy.
* Be willing to accept a risk of pregnancy.
* Be willing to engage in at least two acts of heterosexual vaginal intercourse per cycle.
* Be willing to be randomized to either study treatment.
* Be willing to use the study product as the only method of contraception over the course of the study (with the exception of emergency contraception (EC)), when indicated).
* Be capable of using the study product properly and agree to observe all study directions and requirements.
* Be willing to keep a daily diary to record coital information, product use information, information about the use of other vaginal products, and sign and symptom data for both the subject and her partner.
* Agree not to participate in any other clinical trials during the course of the study with the exception of enrolling in the Amphora™ gel extension study.
* Be willing to give written informed consent to participate in the trial.

Exclusion Criteria:

* Have a history of allergy or sensitivity to spermicides or products containing N-9 (nonoxynol-9).
* Have had three or more urinary tract infections (UTIs) in the past year.
* Have a UTI by urine culture, symptomatic yeast vaginitis, or symptomatic bacterial vaginosis diagnosed by wet mount unless treated and proof of cure is documented.
* Have a history of any recurrent vaginal infections/disorders (either less than or equal to four times in the past year or less than or equal to three times in the previous six months).
* Be pregnant, have a suspected pregnancy, or desire to become pregnant during the course of the study.
* Have a history of infertility or of conditions that may lead to infertility, without subsequent intrauterine pregnancy.
* Have any contraindications to pregnancy (medical condition) or chronic use of medications for which significant evidence of fetal risk exists.
* Have had more than one sexual partner in the last four months.
* Have shared injection drug needles in the past unless has a negative HIV test at least six weeks since last use.
* Have or have been suspected to have HIV infection.
* Have been diagnosed with genital herpes simplex virus (HSV), with the first occurrence (initial episode) within three months prior to screening.
* Have three or more outbreaks of HSV within the last year.
* Have evidence of Chlamydia trachomatis or Neisseria gonorrhoeae unless she and her partner complete treatment and proof of cure is documented.
* Have been diagnosed with any other STDs in the six months prior to the Randomization Visit (with the exception of human papillomavirus (HPV), trichomonas, gonorrhea, adn Chlamydia).
* Be lactating or breastfeeding.
* Have any clinically significant abnormal vaginal bleeding or spotting within the month prior to screening.
* Have any clinically significant abnormal finding on pelvic examination or baseline labs, which in the view of the investigator, precludes her from participating in the trial.
* Have clinically significant signs of vaginal or cervical irritation on pelvic examination.
* Have had vaginal or cervical biopsy or vaginal surgery within three months prior to screening (with the exception of cervical biopsies performed for eligibility determination).
* Have used vaginal or systemic antibiotics or antifungals within 14 days prior to screening or enrollment/randomization, with the exception of systemic antibiotics taken for a UTI and trichomonas diagnosed at screening. Subjects should not have used systemic antibiotics prescribed at the Screening Visit for a UTI within seven days of the enrollment/randomization visit.
* Have had a Depo-Provera® injection in the ten months prior to enrollment.
* Have an abnormal Pap test based on the following criteria:
* Pap test in the past 15 months with ASC-US unless:
* less than 21 years of age;
* a repeat Pap test at least six months later was normal;
* reflex HPV testing was performed and was negative for high-risk HPV; or
* 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;
* Pap test in the past 15 months with LSIL unless:
* less than 21 years of age;
* 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;
* Pap test in the past 15 months with ASC-H, atypical glandular cells, or HSIL 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;
* Pap test in the past 15 months with malignant cells.
* Consume (on average) greater than three drinks of an alcoholic beverage per day.
* Have a past history (within 12 months) or current history which, in the PI's judgment, constitutes of drug abuse (recreational, prescription, or over-the-counter (OTC)).
* Have taken an investigational drug or used an investigational device within the past 30 days.
* Have issues or concerns (in the judgment of the investigator) that may compromise the safety of the subject or confound the reliability of compliance and information acquired in this study.

In addition, in order to be eligible to participate in the trial, potential subjects must state that, to her best knowledge, her sexual partner meets the following criteria:

* Is not infertile.
* Has had untreated chlamydia or gonorrhea in the past six months.
* Has not had more than one sexual partner in the past four months.
* Has no history of allergy or sensitivity to spermicides or products containing N-9.
* Has not been previously diagnosed with or suspected of HIV infection unless he has subsequently had a negative HIV test.
* Has not been known to have engaged in homosexual intercourse in the past five years unless he has had negative HIV test results since then.
* Has not shared injection drug needles in the past unless he has had a negative HIV test at least six weeks since last use.

Primary outcomes:
measure: 6-Month (183 Days) Cumulative Pregnancy Percentage
timeFrame: 183 days
Secondary outcomes:
measure: 6-Month (183 Days) Cumulative Pregnancy Percentage for Subjects With Perfect Use
timeFrame: 183 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, LLC
state: Alabama
city: Little Rock
country: United States
facility: Lynn Institute of the Ozarks
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Berkeley
country: United States
facility: California Family Health Council, Inc.
state: California
city: Los Angeles
country: United States
facility: California Family and Health Council, Inc., LA
state: California
city: Los Angeles
country: United States
facility: California Family Health Council
state: California
city: San Diego
country: United States
facility: Women's Health Care
state: California
city: Denver
country: United States
facility: Downtown Women's Healthcare
state: Colorado
city: Denver
country: United States
facility: Planned Parenthood of the Rocky Mountains
state: Colorado
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Reseach
state: Florida
city: Lake Worth
country: United States
facility: Altus Research
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: North Miami
country: United States
facility: Segal Institute for Clinical Research
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials
state: Florida
city: Decatur
country: United States
facility: Soapstone Center for Clinical Research
state: Georgia
city: Idaho Falls
country: United States
facility: Rosemark WomenCare Specialist
state: Idaho
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Community Physicians
state: Maryland
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: NYU Medical Center Family Planning
state: New York
city: New York
country: United States
facility: Columbia University Medical Center, Division of Family Planning
state: New York
city: New Bern
country: United States
facility: Eastern Carolina Women's Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Planned Parenthood of Northeast Ohio
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center, Reproductive Research Unit
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia Clinical Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital
state: Pennsylvania
city: Corpus Christi
country: United States
facility: Advanced Research Associates
state: Texas
city: Dallas
country: United States
facility: Practice Research Organization
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center - Dept. of OB/GYN
state: Texas
city: Houston
country: United States
facility: TMC Life Research, Inc
state: Texas
city: Irving
country: United States
facility: MacArthur OB/GYN
state: Texas
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
city: Seattle
country: United States
facility: Women's Clinical Research Center
state: Washington
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
state: Republic Tatarstan
city: Rostov-na-Donu
country: Russian Federation
facility: State Budgetary Institution fo Rostov region "Parinatal Center"
state: Rostov Region
city: Ekaterinburg
country: Russian Federation
facility: Ural Scientific Research Institution of Maternity and Child Protection
city: Moscow
country: Russian Federation
facility: Moscow Regional Research Institute of Obstetrics and Gynecology
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #13
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #31
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University named after IM Sechenov
city: Saint Petersburg
country: Russian Federation
facility: Maternity Hospital #17
city: Saint Petersburg
country: Russian Federation
facility: Medical Center "Prime-Rose"LLC
city: Saint Petersburg
country: Russian Federation
facility: The DO Ott Research Institute of Obstetrics and Gynecology
city: Saint-Petersburg
country: Russian Federation
facility: Hospital OrCli
Study officials:
affiliation: Evofem Inc.
name: Kelly Culwell, MD
role: STUDY_DIRECTOR
References: