Trial Outcomes & Findings for Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring in Women at Risk for Pregnancy (MK-8342B-061) (NCT NCT02524288)

Last Updated: 2024-05-17

Results Overview

The Pearl Index is the number of in-treatment pregnancies with a conception date in any of the in-treatment cycles, divided by all treatment cycles in each participant from the first treatment cycle to the last treatment cycle (due either to discontinuation or completion), regardless of whether a treatment cycle was "at risk" or not. One woman-year is defined as 13 treatment cycles x 28 days. These efficacy results should be interpreted with caution. Due to the discontinuation of product development and early trial termination, the number of "at risk" treatment cycles in the denominator is based on uncleaned diary data.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1941 participants

Primary outcome timeframe

Up to 1 year (13 28-day cycles)

Results posted on

2024-05-17

Participant Flow

Participant milestones

Participant milestones
Measure	ENG-E2 125 μg/300 μg Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Overall Study STARTED	1941
Overall Study Treated	1936
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1941

Reasons for withdrawal

Reasons for withdrawal
Measure	ENG-E2 125 μg/300 μg Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Overall Study Adverse Event	115
Overall Study Lost to Follow-up	216
Overall Study Non-Compliance With Protocol	32
Overall Study Non-Compliance With Study Drug	14
Overall Study Pregnancy Wish	6
Overall Study Protocol Violation	6
Overall Study Screen Failure	2
Overall Study Site Discontinued Study Participation	1
Overall Study Study Terminated By Sponsor	1417
Overall Study Subject Moved	32
Overall Study Withdrawal by Subject	76
Overall Study Pregnancy	22
Overall Study Physician Decision	2

Baseline Characteristics

Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring in Women at Risk for Pregnancy (MK-8342B-061)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ENG-E2 125 μg/300 μg n=1941 Participants Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Age, Continuous	27.6 Years STANDARD_DEVIATION 6.2 • n=99 Participants
Sex: Female, Male Female	1941 Participants n=99 Participants
Sex: Female, Male Male	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: Up to 1 year (13 28-day cycles)

Population: All participants assigned to treatment who inserted at least 1 ENG-E2 ring, and who had at least 1 "at risk" treatment cycle, or participants with a treatment cycle (at risk or not) in which a pregnancy had occurred (i.e., treatment cycle containing an estimated conception date for a pregnancy).

Outcome measures

Outcome measures
Measure	ENG-E2 125 μg/300 μg n=1574 Participants Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index)	4.32 Pregnancies per 100 woman years

PRIMARY outcome

Timeframe: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)

Population: All randomized participants in whom at least 1 vaginal ring was inserted.

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 pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Outcome measures

Outcome measures
Measure	ENG-E2 125 μg/300 μg n=1936 Participants Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Number of Participants With One or More Adverse Events (AEs)	830 Participants

PRIMARY outcome

Timeframe: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)

Population: All randomized participants in whom at least 1 vaginal ring was inserted.

Outcome measures

Outcome measures
Measure	ENG-E2 125 μg/300 μg n=1936 Participants Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Number of Participants Who Discontinued Treatment Due to an AE	112 Participants

PRIMARY outcome

Timeframe: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)

Population: All randomized participants in whom at least 1 vaginal ring was inserted.

Outcome measures

Outcome measures
Measure	ENG-E2 125 μg/300 μg n=1936 Participants Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Number of Participants With One or More Drug-related AEs	439 Participants

PRIMARY outcome

Timeframe: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)

Population: All randomized participants in whom at least 1 vaginal ring was inserted.

Outcome measures

Outcome measures
Measure	ENG-E2 125 μg/300 μg n=1936 Participants Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Number of Participants Who Discontinued Treatment Due to a Drug-related AE	91 Participants

Adverse Events

ENG-E2 125 μg/300 μg

Serious events: 12 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ENG-E2 125 μg/300 μg n=1936 participants at risk Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Congenital, familial and genetic disorders Vitello-intestinal duct remnant	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Endocrine disorders Goitre	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Gastrointestinal disorders Rectal haemorrhage	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Infections and infestations Appendicitis	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Infections and infestations Diverticulitis	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Infections and infestations Pneumonia	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Injury, poisoning and procedural complications Concussion	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Pregnancy, puerperium and perinatal conditions Ruptured ectopic pregnancy	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Psychiatric disorders Alcohol withdrawal syndrome	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Psychiatric disorders Depression	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.05% 1/1936 • Number of events 1 • From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) All randomized participants in whom at least 1 vaginal ring was inserted.

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Publication restrictions are in place

Restriction type: OTHER