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)

NCT02616146 | Terminated Phase 3 Results

• 3 other identifiers: 8342B-0622014-002208-26MK-1029-006
• Study Type: interventional
• Target: 2,016
• Locations: 14 countries
• Sites: 14

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.

Conditions

Contraception

Outcome Measures

Primary Outcomes (3)

• Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index)

  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.

  Up to 1 year (13 28-day cycles)

• Number of Participants Who Experienced an Adverse Event (AE)

  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.

  Up to 1 year

• Number of Participants Who Discontinued Treatment Due to an AE

  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.

  Up to 1 year

Secondary Outcomes (2)

• Number of Participants With Breakthrough Bleeding/Spotting (BTB-S), by Cycle

  Up to 1 year

• Number of Participants With Absence of Withdrawal Bleeding (AWB), by Cycle

  Up to 1 year

Study Arms (2)

ENG-E2 125 μg/300 μg

EXPERIMENTAL

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

LNG-EE 150 μg/30 μg

ACTIVE COMPARATOR

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

Interventions

ENG-E2 125 μg/300 μg vaginal ring DRUG

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.

Also known as: Etonogestrel + 17β-Estradiol Vaginal Ring

ENG-E2 125 μg/300 μg

LNG-EE 150 μg/30 μg COC DRUG

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.

Also known as: Levonorgestrel-Ethinyl Estradiol COC

LNG-EE 150 μg/30 μg

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Organon and Co: lead

Study Sites (14)

MSD Osterreich GmbH

Vienna, Austria

Location

Merck Sharp & Dohme

San José, Costa Rica

Location

Merck Sharp & Dohme

Glostrup Municipality, Denmark

Location

MSD Finland Oy

Espoo, Finland

Location

Merck Sharp & Dohme GmbH

Haar, Germany

Location

MSD Pharma Hungary Kft.

Budapest, Hungary

Location

MSD Italia S.r.l.

Rome, Italy

Location

MSD

Mexico City, Mexico

Location

Merck Sharp & Dohme BV

Haarlem, Netherlands

Location

MSD Norge A/S

Drammen, Norway

Location

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

Lima, Peru

Location

MSD Polska Sp. Z o.o.

Warsaw, Poland

Location

MSD (Pty) LTD South Africa

Midrand, South Africa

Location

MSD Sweden

Stockholm, Sweden

Location

MeSH Terms

Interventions

Contraceptive Devices, Female; etonogestrel

Intervention Hierarchy (Ancestors)

Contraceptive Devices; Equipment and Supplies

Limitations and Caveats

Because the trial was terminated early, participant diary data used for efficacy analysis and bleeding analysis were not verified. These results should be interpreted with caution. No hypothesis testing was performed.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: November 26, 2015
• Study Start: December 1, 2015
• Primary Completion: October 6, 2016
• Study Completion: October 6, 2016
• Last Updated: May 17, 2024
• Results First Posted: January 18, 2019

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); DK (1); ZA (1); ME (1); AU (1); HU (1); DE (1); SE (1); IT (1); FI (1); PE (1); PL (1); CO (1); NL (1)