Clinical trial NCT02616146: Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring and Levonorgestrel-Ethinyl Estradiol Combined Oral Contraceptive in Adult Women at Risk for Pregnancy (MK-8342B-062)
Official title: A Phase 3, Randomized, Active-Comparator Controlled Clinical Trial to Study the Contraceptive Efficacy and Safety of the MK-8342B (Etonogestrel + 17β-Estradiol) Vaginal Ring and the Levonorgestrel-Ethinyl Estradiol (LNG-EE) 150/30 μg Combined Oral Contraceptive (COC) in Healthy Women 18 Years of Age and Older, at Risk for Pregnancy.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Contraception
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2015-11-26
Enrollment: 2016
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the contraceptive efficacy of the etonogestrel + 17β-estradiol (ENG-E2) vaginal ring in women between 18 and 35 years of age based on the number of in-treatment pregnancies as expressed by the Pearl Index (PI). The study will also assess the safety and tolerability of ENG-E2 vaginal ring. The levonorgestrel-ethinyl estradiol (LNG-EE) 150/30 μg combined oral contraceptive (COC) will be used as the active comparator.


Eligibility criteria: Inclusion Criteria:

* Premenopausal female at risk for pregnancy and seeking contraception.
* Willing to use a hormonal contraceptive vaginal ring for up to 13 treatment cycles, and not intending to use any other form of contraception.
* Body mass index (BMI) of ≥18 and \<38 kg/m\^2.
* In good physical and mental health, based upon the medical judgment of the investigator.
* Willing to adhere to use of vaginal ring and all required trial procedures.

Exclusion Criteria:

* Cardiovascular risks and disorders, including history of venous thromboembolic \[VTE\] events, arterial thrombotic or thromboembolic \[ATE\] events, transient ischemic attack, angina pectoris, or claudication; at higher risk of VTE events due to recent prolonged immobilization, plans for surgery requiring prolonged immobilization, or a hereditary or acquired predisposition or elevated risk for venous or arterial thrombosis; currently smoking or uses tobacco/nicotine containing products and is ≥35 years of age; uncontrolled or severe hypertension; history of severe dyslipoproteinemia; \<35 years of age with a history of migraine with aura or focal neurological symptoms or ≥35 years of age with a history of migraines with or without aura or focal neurologic symptoms; diabetes mellitus with end-organ involvement or \>20 years duration; multiple cardiovascular risk factors such as ≥35 years of age, obesity, inadequately controlled hypertension, use of tobacco/ nicotine products, or inadequately controlled diabetes.
* Gastrointestinal disorders, including history of pancreatitis associated with severe hypertriglyceridemia; clinically significant liver disease, including active viral hepatitis or cirrhosis; history of malabsorptive bariatric surgery.
* Other medical disorders, including history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer; any disease that may worsen under hormonal treatment such as disturbances in bile flow, systemic lupus erythematosus, pemphigoid gestationis or idiopathic icterus during previous pregnancy, middle-ear deafness, Sydenham chorea, or porphyria; known allergy/sensitivity or contraindication to the investigational products or their excipients; history of drug or alcohol abuse or dependence.
* Recent, current, or suspected pregnancy; or has not had at least 2 menstrual cycles or has not completed two 28-day cycles of a hormonal contraceptive following a recent pregnancy; or is breastfeeding.
* Gynecologic conditions: has gonorrhea, chlamydia, or trichomonas or symptomatic vaginitis/cervicitis; has abnormal cervical Pap test or positive high-risk human papillomavirus (HPV) test at screening or documented within 3 years of screening; currently using an intrauterine device/intrauterine system (IUD/IUS) or contraceptive implant; within past 6 months has had undiagnosed (unexplained) abnormal vaginal bleeding or any abnormal vaginal bleeding expected to recur during trial; has stage 4 pelvic organ prolapse (1 cm beyond introitus) or lesser degrees of prolapse with history of difficulty retaining tampons, vaginal rings, or other products within vagina.
* Has used investigational drug and/or participated in other clinical trial within past 8 weeks.

Primary outcomes:
measure: Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index)
timeFrame: Up to 1 year (13 28-day cycles)
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to 1 year
measure: Number of Participants Who Discontinued Treatment Due to an AE
timeFrame: Up to 1 year
Secondary outcomes:
measure: Number of Participants With Breakthrough Bleeding/Spotting (BTB-S), by Cycle
timeFrame: Up to 1 year
measure: Number of Participants With Absence of Withdrawal Bleeding (AWB), by Cycle
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: MSD Osterreich GmbH
city: San Jose
country: Costa Rica
facility: Merck Sharp & Dohme
city: Glostrup
country: Denmark
facility: Merck Sharp & Dohme
city: Espoo
country: Finland
facility: MSD Finland Oy
city: Haar
country: Germany
facility: Merck Sharp & Dohme GmbH
city: Budapest
country: Hungary
facility: MSD Pharma Hungary Kft.
city: Rome
country: Italy
facility: MSD Italia S.r.l.
city: Mexico City
country: Mexico
facility: MSD
city: Haarlem
country: Netherlands
facility: Merck Sharp & Dohme BV
city: Drammen
country: Norway
facility: MSD Norge A/S
city: Lima
country: Peru
facility: Merck Sharp & Dohme, Peru S.R.L.
city: Warsaw
country: Poland
facility: MSD Polska Sp. Z o.o.
city: Midrand
country: South Africa
facility: MSD (Pty) LTD South Africa
city: Stockholm
country: Sweden
facility: MSD Sweden
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: