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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)

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ClinicalTrials.gov Identifier: NCT02616146
Recruitment Status : Terminated (Study terminated by Sponsor as a result of a business decision to discontinue the development program for MK-8342B for reasons unrelated to safety or efficacy.)
First Posted : November 26, 2015
Results First Posted : January 18, 2019
Last Update Posted : January 18, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Contraception
Interventions Drug: ENG-E2 125 μg/300 μg vaginal ring
Drug: LNG-EE 150 μg/30 μg COC
Enrollment 2016
Recruitment Details Note: One participant less than 18 years of age was inadvertently randomized and received study medication. She was discontinued from the study due to the major protocol violation.
Pre-assignment Details  
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Hide Arm/Group Description Participants were to receive up to 13 cycles of etonogestrel + 17β-estradiol (ENG-E2) 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days. Participants were to receive up to 13 cycles of levonorgestrel-ethinyl estradiol (LNG-EE) 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.
Period Title: Overall Study
Started 1512 504
Completed 0 [1] 0 [2]
Not Completed 1512 504
Reason Not Completed
Adverse Event             64             24
Lost to Follow-up             23             13
Non-compliance with study protocol             2             0
Non-compliance with study drug             4             2
Pregnancy             2             2
Pregnancy wish             3             0
Protocol Violation             6             3
Study terminated by sponsor             1372             432
Participant moved             4             3
Withdrawal by Subject             30             24
Physician Decision             2             1
[1]
Due to termination of study, ENG-E2 reporting group received only up to 10 cycles of treatment.
[2]
Due to termination of study, LNG-EE reporting group received only up to 9 cycles of treatment.
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg Total
Hide Arm/Group Description Participants were to receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days. Participants were to receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval. Total of all reporting groups
Overall Number of Baseline Participants 1512 504 2016
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1512 participants 504 participants 2016 participants
27.5  (6.3) 27.5  (6.3) 27.5  (6.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1512 participants 504 participants 2016 participants
Female
1512
 100.0%
504
 100.0%
2016
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index)
Hide Description 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.
Time Frame Up to 1 year (13 28-day cycles)
Hide Outcome Measure Data
Hide Analysis Population Description
restricted Full Analysis Set (rFAS) population, defined as the population of women with at least one “at risk” treatment cycle without documented use of hormonal or nonhormonal backup contraception during the cycle, or participants with a treatment cycle (at risk or not) in which a pregnancy has occurred.
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Hide Arm/Group Description:
Participants were to receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Participants were to receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.
Overall Number of Participants Analyzed 1266 404
Measure Type: Number
Unit of Measure: Pregnancies per 100 woman years
1.54 2.93
2.Primary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description 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.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
This primary endpoint was based on all randomized participants in whom at least one vaginal ring was inserted or one comparator tablet was ingested.
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Hide Arm/Group Description:
Participants were to receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Participants were to receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.
Overall Number of Participants Analyzed 1504 492
Measure Type: Count of Participants
Unit of Measure: Participants
530
  35.2%
140
  28.5%
3.Primary Outcome
Title Number of Participants Who Discontinued Treatment Due to an AE
Hide Description 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.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
This primary endpoint was based on all randomized participants in whom at least one vaginal ring was inserted or one comparator tablet was ingested.
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Hide Arm/Group Description:
Participants were to receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Participants were to receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.
Overall Number of Participants Analyzed 1504 492
Measure Type: Count of Participants
Unit of Measure: Participants
61
   4.1%
23
   4.7%
4.Secondary Outcome
Title Number of Participants With Breakthrough Bleeding/Spotting (BTB-S), by Cycle
Hide Description 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.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS Evaluable population, defined as a subset of FAS population that met the following criteria: a) No more than 2 consecutive days with missing bleeding data on Daily Diary unless there was at least one day with BTB-S during the ring-use interval; and b) treatment cycle length (including hormone-free interval) is between 22 and 35 days, inclusive.
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Hide Arm/Group Description:
Participants were to receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Participants were to receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.
Overall Number of Participants Analyzed 1504 492
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 2 Number Analyzed 1263 participants 375 participants
166
  13.1%
54
  14.4%
Cycle 3 Number Analyzed 1001 participants 295 participants
112
  11.2%
36
  12.2%
Cycle 4 Number Analyzed 755 participants 231 participants
79
  10.5%
20
   8.7%
Cycle 5 Number Analyzed 483 participants 155 participants
42
   8.7%
13
   8.4%
Cycle 6 Number Analyzed 295 participants 88 participants
29
   9.8%
8
   9.1%
Cycle 7 Number Analyzed 125 participants 40 participants
13
  10.4%
7
  17.5%
Cycle 8 Number Analyzed 36 participants 10 participants
8
  22.2%
2
  20.0%
Cycle 9 Number Analyzed 7 participants 1 participants
1
  14.3%
0
   0.0%
5.Secondary Outcome
Title Number of Participants With Absence of Withdrawal Bleeding (AWB), by Cycle
Hide Description 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.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS Evaluable population, defined as a subset of FAS population that met the following criteria: a) No more than 2 consecutive days with missing bleeding data on Daily Diary unless there was at least one day with BTB-S during the ring-use interval; and b) treatment cycle length (including hormone-free interval) is between 22 and 35 days, inclusive.
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Hide Arm/Group Description:
Participants were to receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Participants were to receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.
Overall Number of Participants Analyzed 1504 492
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1 Number Analyzed 1448 participants 441 participants
76
   5.2%
15
   3.4%
Cycle 2 Number Analyzed 1263 participants 375 participants
34
   2.7%
10
   2.7%
Cycle 3 Number Analyzed 1001 participants 295 participants
26
   2.6%
10
   3.4%
Cycle 4 Number Analyzed 755 participants 231 participants
17
   2.3%
6
   2.6%
Cycle 5 Number Analyzed 483 participants 155 participants
3
   0.6%
0
   0.0%
Cycle 6 Number Analyzed 295 participants 88 participants
3
   1.0%
1
   1.1%
Cycle 7 Number Analyzed 125 participants 40 participants
0
   0.0%
2
   5.0%
Cycle 8 Number Analyzed 36 participants 10 participants
0
   0.0%
1
  10.0%
Cycle 9 Number Analyzed 7 participants 1 participants
0
   0.0%
0
   0.0%
Time Frame Up to 1 year
Adverse Event Reporting Description Safety analysis was based on all randomized participants in whom at least 1 vaginal ring was inserted or one comparator tablet was ingested. 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.
 
Arm/Group Title ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Hide Arm/Group Description Participants were to receive up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle was to consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days. Participants were to receive up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle was to consist of one tablet per day for 21 days, followed a 7-day tablet-free interval.
All-Cause Mortality
ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/1504 (0.53%)      3/492 (0.61%)    
Eye disorders     
Visual acuity reduced  1  0/1504 (0.00%)  0 1/492 (0.20%)  1
Infections and infestations     
Dengue fever  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Gastrointestinal infection  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Influenza  1  0/1504 (0.00%)  0 1/492 (0.20%)  1
Urinary tract infection  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Injury, poisoning and procedural complications     
Foreign body  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Nervous system disorders     
Epilepsy  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Syncope  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Product Issues     
Device deployment issue  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Renal and urinary disorders     
Cystitis haemorrhagic  1  1/1504 (0.07%)  1 0/492 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  0/1504 (0.00%)  0 1/492 (0.20%)  1
Vascular disorders     
Deep vein thrombosis  1  0/1504 (0.00%)  0 1/492 (0.20%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ENG-E2 125 μg/300 μg LNG-EE 150 μg/30 μg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   116/1504 (7.71%)      40/492 (8.13%)    
Nervous system disorders     
Headache  1  116/1504 (7.71%)  180 40/492 (8.13%)  68
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02616146     History of Changes
Other Study ID Numbers: 8342B-062
2014-002208-26 ( EudraCT Number )
MK-1029-006 ( Other Identifier: Merck Protocol Number )
First Submitted: November 24, 2015
First Posted: November 26, 2015
Results First Submitted: October 13, 2017
Results First Posted: January 18, 2019
Last Update Posted: January 18, 2019