Clinical Trial Results:
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.
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Summary
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EudraCT number |
2014-002208-26 |
Trial protocol |
NO SE DE FI DK AT ES NL HU PL CZ IT |
Global end of trial date |
06 Oct 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Sep 2017
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First version publication date |
28 Sep 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
8342B-062
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02616146 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Merck Registration: MK-8342B-062 | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Oct 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Oct 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Oct 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
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 levonorgestrelethinyl estradiol (LNG-EE) 150/30 μg combined oral contraceptive (COC) will be used as the active comparator.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Dec 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 6
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Country: Number of subjects enrolled |
Chile: 188
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Country: Number of subjects enrolled |
Colombia: 93
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Country: Number of subjects enrolled |
Costa Rica: 35
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Country: Number of subjects enrolled |
Czech Republic: 173
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Country: Number of subjects enrolled |
Denmark: 81
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Country: Number of subjects enrolled |
Finland: 168
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Country: Number of subjects enrolled |
Germany: 143
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Country: Number of subjects enrolled |
Hungary: 122
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Mexico: 118
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Country: Number of subjects enrolled |
Netherlands: 48
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Country: Number of subjects enrolled |
Norway: 175
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Country: Number of subjects enrolled |
Peru: 6
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Country: Number of subjects enrolled |
Poland: 225
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Country: Number of subjects enrolled |
Russian Federation: 224
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Country: Number of subjects enrolled |
South Africa: 97
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Country: Number of subjects enrolled |
Spain: 68
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Country: Number of subjects enrolled |
Sweden: 40
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Worldwide total number of subjects |
2016
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EEA total number of subjects |
1255
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
2015
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Note: One subject 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. | |||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
This study enrolled in healthy, premenopausal women 18 years of age and older who were at risk of pregnancy. Additional inclusion and exclusion criteria applied. | |||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ENG-E2 125 μg/300 μg | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Etonogestrel + 17β-Estradiol Vaginal Ring
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Investigational medicinal product code |
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Other name |
MK-8342B
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Pharmaceutical forms |
Vaginal delivery system
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Routes of administration |
Vaginal use
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Dosage and administration details |
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.
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Arm title
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LNG-EE 150 μg/30 μg | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle consisted of one tablet per day for 21 days, followed a 7-day tablet-free interval. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Levonorgestrel-Ethinyl Estradiol COC
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
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.
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Baseline characteristics reporting groups
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Reporting group title |
ENG-E2 125 μg/300 μg
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Reporting group description |
Participants received up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
LNG-EE 150 μg/30 μg
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Reporting group description |
Participants received up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle consisted of one tablet per day for 21 days, followed a 7-day tablet-free interval. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ENG-E2 125 μg/300 μg
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Reporting group description |
Participants received up to 13 cycles of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | ||
Reporting group title |
LNG-EE 150 μg/30 μg
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Reporting group description |
Participants received up to 13 cycles of LNG-EE 150 μg/30 μg. Each cycle consisted of one tablet per day for 21 days, followed a 7-day tablet-free interval. | ||
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End point title |
Number of In-Treatment Pregnancies per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index) [1] | ||||||||||||
End point 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). This primary endpoint was based on the 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. These results should be interpreted with caution because the trial was terminated early and the subject diary data used for calculation of the Pearl Index were not verified.
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End point type |
Primary
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End point timeframe |
Up to 1 year (13 28-day cycles)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical analyses were performed for Number of In-Treatment Pregnancies per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index). |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants Who Experienced an Adverse Event (AE) [2] | |||||||||
End point 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 pre-existing condition that is temporally associated with the use of the Sponsor’s product, is also an AE. This primary endpoint was based on all randomized participants in whom at least 1 vaginal ring was inserted or one comparator tablet was ingested.
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End point type |
Primary
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End point timeframe |
Up to 1 year
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical analyses were performed for Number of Participants Who Experienced an Adverse Event (AE) |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants Who Discontinued Treatment Due to an AE [3] | |||||||||
End point 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 pre-existing condition that is temporally associated with the use of the Sponsor’s product, is also an AE. This primary endpoint was based on all randomized participants in whom at least 1 vaginal ring was inserted or one comparator tablet was ingested.
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End point type |
Primary
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End point timeframe |
Up to 1 year
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical analyses were performed for Number of Participants Who Discontinued Treatment Due to an AE |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants With Breakthrough Bleeding/Spotting (BTB-S), by Cycle | |||||||||||||||||||||||||||||||||
End point 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. This secondary endpoint was based on the FAS Evaluable population, defined as a subset of the FAS population that met the following criteria: a) No more than 2 consecutive days with missing bleeding data on the Daily Diary unless there was at least one day with BTB-S during the ring-use interval; and b) Treatment cycle length (including the hormone-free interval) is between 22 and 35 days, inclusive. These results should be interpreted with caution because the trial was terminated early and the subject diary data used for calculation of these results were not verified. No hypothesis testing was performed.
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End point type |
Secondary
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End point timeframe |
Up to 1 year
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 1 year
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Adverse event reporting additional description |
All randomized participants in whom at least 1 vaginal ring was inserted or one comparator tablet was ingested.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
ENG-E2 125 µg/300 µg
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Reporting group description |
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Reporting group title |
LNG-EE 150 µg/30 µg COC
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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01 Apr 2016 |
Amendment 1. The primary reasons for this amendment were: to emphasize that the discontinuation visit should be
scheduled no sooner than 14 days and up to 17 days after
discontinuation of study medication; to add a urine
pregnancy test to be performed at home at the time of the
safety follow-up phone visit if a discontinued participant refuses to return to clinic; and to clarify that safety labs (hematology, chemistry, and urinalysis) should be performed at discontinuation if not already performed at Visit 5 (i.e.,
participant discontinues prior to V5). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| This study was terminated by the Sponsor as a result of a business decision to discontinue the development program for MK-8342B for reasons unrelated to safety or efficacy outcomes. | |||||||
