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)

• ClinicalTrials.gov Identifier: NCT02616146
• Recruitment Status: Terminated
• First Posted: November 26, 2015
• Results First Posted: January 18, 2019
• Last Update Posted: January 18, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Contraception	Drug: ENG-E2 125 μg/300 μg vaginal ring; Drug: LNG-EE 150 μg/30 μg COC	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2016 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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.
• Actual Study Start Date: December 1, 2015
• Actual Primary Completion Date: October 6, 2016
• Actual Study Completion Date: October 6, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: ENG-E2 125 μg/300 μg; Participants will receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle will consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.	Drug: ENG-E2 125 μg/300 μg vaginal ring; Up to 13 cycles of ENG-E2 125 μg/300 μg administered intravaginally, each cycle consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.; Other Name: Etonogestrel + 17β-Estradiol Vaginal Ring
Active Comparator: LNG-EE 150 μg/30 μg; Participants will receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle will consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.	Drug: LNG-EE 150 μg/30 μg COC; Up to 13 cycles of LNG-EE 150 μg/30 μg administered orally, each cycle consisting of one tablet per day for 21 days, followed a 7-day tablet-free interval.; Other Name: Levonorgestrel-Ethinyl Estradiol COC

Outcome Measures

Primary Outcome Measures :

1. Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index) [ Time Frame: Up to 1 year (13 28-day cycles) ]
   The Primary Efficacy Outcome Measure for this study was contraceptive efficacy, or the prevention of in-treatment pregnancy. The total incidence of in-treatment pregnancies was expressed as the Pearl Index, which is defined as the number of in-treatment pregnancies per 100 woman-years of exposure (one woman-year defined as a period of 365.25 days). NOTE: Due to early termination of this study, the ENG-E2 reporting group received only up to 10 cycles of treatment, and the LNG-EE reporting group received only up to 9 cycles of treatment.
2. Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 1 year ]
   An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. NOTE: Due to early termination of this study, the ENG-E2 reporting group received only up to 10 cycles of treatment, and the LNG-EE reporting group received only up to 9 cycles of treatment.
3. Number of Participants Who Discontinued Treatment Due to an AE [ Time Frame: Up to 1 year ]
   An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. NOTE: Due to early termination of this study, the ENG-E2 reporting group received only up to 10 cycles of treatment, and the LNG-EE reporting group received only up to 9 cycles of treatment.

Secondary Outcome Measures :

1. Number of Participants With Breakthrough Bleeding/Spotting (BTB-S), by Cycle [ Time Frame: Up to 1 year ]
   BTB-S was considered any bleeding/spotting that occurred during expected non-bleeding interval that was neither early nor continued withdrawal bleeding. BTB-S was classified as follows: Bleeding = any bloody vaginal discharge that required one or more sanitary pads or tampons per day; Spotting = any bloody vaginal discharge that required no sanitary pads or tampons per day. NOTE: Due to early termination of this study, the ENG-E2 reporting group received only up to 10 cycles of treatment, and the LNG-EE reporting group received only up to 9 cycles of treatment.
2. Number of Participants With Absence of Withdrawal Bleeding (AWB), by Cycle [ Time Frame: Up to 1 year ]
   Participants were asked to keep a daily diary to record vaginal bleeding events. AWB was defined as no bleeding/spotting during the expected bleeding period. NOTE: Due to early termination of this study, the ENG-E2 reporting group received only up to 10 cycles of treatment, and the LNG-EE reporting group received only up to 9 cycles of treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Austria

MSD Osterreich GmbH

Vienna, Austria

Costa Rica

Merck Sharp & Dohme

San Jose, Costa Rica

Denmark

Merck Sharp & Dohme

Glostrup, Denmark

Finland

MSD Finland Oy

Espoo, Finland

Germany

Merck Sharp & Dohme GmbH

Haar, Germany

Hungary

MSD Pharma Hungary Kft.

Budapest, Hungary

Italy

MSD Italia S.r.l.

Rome, Italy

Mexico

MSD

Mexico City, Mexico

Netherlands

Merck Sharp & Dohme BV

Haarlem, Netherlands

Norway

MSD Norge A/S

Drammen, Norway

Peru

Merck Sharp & Dohme, Peru S.R.L.

Lima, Peru

Poland

MSD Polska Sp. Z o.o.

Warsaw, Poland

South Africa

MSD (Pty) LTD South Africa

Midrand, South Africa

Sweden

MSD Sweden

Stockholm, Sweden

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT02616146
• Other Study ID Numbers: 8342B-062; 2014-002208-26 ( EudraCT Number ); MK-1029-006 ( Other Identifier: Merck Protocol Number )
• First Posted: November 26, 2015
• Results First Posted: January 18, 2019
• Last Update Posted: January 18, 2019
• Last Verified: August 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Estradiol 3-benzoate; Estradiol 17 beta-cypionate; Levonorgestrel; Etonogestrel; Ethinyl estradiol, levonorgestrel drug combination; Estradiol; Polyestradiol phosphate; Ethinyl Estradiol; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Contraceptives, Oral, Combined