Clinical Trial Results:
A Phase 3 Randomized, Double-blind, Placebo-Controlled Trial to Study the Efficacy and Safety of MK-8342B (ENG-E2 vaginal ring) in Women with Moderate to Severe Primary Dysmenorrhea.
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Summary
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EudraCT number |
2015-004326-34 |
Trial protocol |
SE PL IT |
Global end of trial date |
12 Sep 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
20 May 2018
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First version publication date |
20 May 2018
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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-060
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02668822 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Merck Study Number: MK-8342B-060 | ||
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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 |
ClinicalTrialsDisclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
ClinicalTrialsDisclosure, 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 |
12 Sep 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Sep 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 was to evaluate the efficacy of the etonogestrel (ENG) + 17β-estradiol (E2) (MK-8342B) vaginal ring compared to placebo vaginal ring in the treatment of dysmenorrhea at Treatment Cycle 2. This study was also to assess the safety and tolerability of the ENG-E2 vaginal rings over 4 treatment cycles. Primary hypothesis: Relative to the placebo ring, the ENG-E2 vaginal ring results in a greater proportion of participants with a ≥3-point reduction in peak pelvic pain score and no increase in the number of rescue pain relief (ibuprofen) tablets taken at Treatment Cycle 2 as compared to baseline
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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 |
Ibuprofen 400 mg every 4 hours as needed for pelvic pain/ cramping | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Feb 2016
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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 |
Chile: 5
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Country: Number of subjects enrolled |
Poland: 1
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Country: Number of subjects enrolled |
Russian Federation: 2
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Country: Number of subjects enrolled |
Sweden: 3
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Country: Number of subjects enrolled |
United States: 7
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Worldwide total number of subjects |
18
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EEA total number of subjects |
4
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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) |
0
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Adults (18-64 years) |
18
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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 |
The study was to involve 4 treatment cycles after a screening period. Each treatment cycle lasted 28 days (21 days of ring use followed by a 7-day ring-free interval). The 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. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Post-menarcheal female participants aged 50 years and younger with moderate to severe primary dysmenorrhea were enrolled in this study. Other inclusion/exclusion criteria applied. | ||||||||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
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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 125 μg + E2 300 μg (MK-8342B) | ||||||||||||||||||
Arm description |
Participants received up to 4 cycles of etonogestrel-17β estradiol (ENG-E2) at a daily dose of 125 μg/300 μg via vaginal ring. Each cycle consisted of 21 days of MK-8342B vaginal ring use followed by 7 ring-free days. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
ENG-E2 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 |
Vaginal ring inserted for 21 days then 7 days ring-free
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Investigational medicinal product name |
Ibuprofen
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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 |
400 mg as needed for cramps
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
Participants received up to 4 cycles of placebo via vaginal ring. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Ibuprofen
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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 |
400 mg as needed for cramps
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Investigational medicinal product name |
Placebo for ENG-E2 vaginal ring
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Investigational medicinal product code |
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Other name |
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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 |
Vaginal ring inserted for 21 days then 7 days ring-free
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Baseline characteristics reporting groups
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Reporting group title |
ENG 125 μg + E2 300 μg (MK-8342B)
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Reporting group description |
Participants received up to 4 cycles of etonogestrel-17β estradiol (ENG-E2) at a daily dose of 125 μg/300 μg via vaginal ring. Each cycle consisted of 21 days of MK-8342B vaginal ring use followed by 7 ring-free days. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received up to 4 cycles of placebo via vaginal ring. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ENG 125 μg + E2 300 μg (MK-8342B)
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Reporting group description |
Participants received up to 4 cycles of etonogestrel-17β estradiol (ENG-E2) at a daily dose of 125 μg/300 μg via vaginal ring. Each cycle consisted of 21 days of MK-8342B vaginal ring use followed by 7 ring-free days. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received up to 4 cycles of placebo via vaginal ring. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days. | ||
Subject analysis set title |
ENG 125 μg + E2 300 μg (MK-8342B)- Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants in whom a vaginal ring was inserted
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Subject analysis set title |
Placebo - Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants in whom a vaginal ring was inserted
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Subject analysis set title |
ENG 125 μg + E2 300 μg (MK-8342B) - Efficacy
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The population was to consist of all participants in whom a vaginal ring was inserted & who had ≥1 day of diary entry each within a 4-day cramping window during a baseline cycle & a treatment cycle. Due to termination, the committee to determine cramping windows was not assembled, cramping windows were not determined & data could not be analyzed.
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Subject analysis set title |
Placebo - Efficacy
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The population was to consist of all participants in whom a vaginal ring was inserted & who had ≥1 day of diary entry each within a 4-day cramping window during a baseline cycle & a treatment cycle. Due to termination, the committee to determine cramping windows was not assembled, cramping windows were not determined & data could not be analyzed.
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End point title |
Percentage of Participants With ≥3 point Reduction in Peak Pelvic Pain Score and No Increase in Number of Ibuprofen Tablets Taken at Treatment Cycle 2, Compared to Baseline [1] | ||||||||||||
End point description |
Participants were asked to rate their worst pain or cramps in the past 24 hours on a scale of 0 to 10 (0=No pain or cramps to 10=Extreme pain or cramps) and to indicate the number of ibuprofen tablets they took during the 4-day cramping window. The peak pelvic pain score was to be calculated as the highest (daily) pelvic pain score observed within the cramping window of the cycle and the total number of ibuprofen tablets taken was to be based on the 4-day cramping window. The baseline peak pelvic pain score and number of ibuprofen tablets taken were to be defined as the mean value of the 2 peak pelvic pain scores and the mean value of the total number of ibuprofen tablets taken during the cramping window of each of the 2 menstruations during the screening period, respectively. The percentage of participants with a reduction in peak pelvic pain score of ≥3 points and no increase in the use of ibuprofen at Treatment Cycle 2 as compared to baseline was to be presented.
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End point type |
Primary
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End point timeframe |
Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
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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: Efficacy data could not be analyzed as cramping windows were not determined due to early trial termination |
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| Notes [2] - Study terminated [3] - Study terminated |
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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) [4] | ||||||||||||
End point description |
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the
use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who experienced an AE is presented.
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End point type |
Primary
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End point timeframe |
Up to approximately 126 days
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| Notes [4] - 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: Statistical analyses were not conducted for this safety endpoint due to early trial termination |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants Who Discontinued Study Treatment Due to an AE [5] | ||||||||||||
End point description |
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who discontinued study treatment due an AE is presented.
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End point type |
Primary
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End point timeframe |
Up to approximately 112 days
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| Notes [5] - 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: Statistical analyses were not conducted for this safety endpoint due to early trial termination |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Peak Pelvic Pain Score at Treatment Cycle 2 | ||||||||||||
End point description |
Participants were asked to rate their worst pain or cramps in the past 24 hours on a scale of 0 to 10 (0=No pain or cramps to 10=Extreme pain or cramps). The peak pelvic pain score was to be calculated as the highest (daily) pelvic pain score observed within the 4-day cramping window of the cycle. The baseline peak pelvic pain score was to be defined as the mean value of the 2 peak pelvic pain scores during the cramping window of each of the 2 menstruations during the screening period. The change from baseline in peak pelvic pain score at Treatment Cycle 2 was to be presented.
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End point type |
Secondary
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End point timeframe |
Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
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| Notes [6] - Study terminated [7] - Study terminated |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in the Number of Days with No Impact on Items of Physical, Work/School and Social/Leisure Activities at Treatment Cycle 2 | ||||||||||||
End point description |
Participants were asked to indicate how much pain or cramps limited their physical, work/school and social/leisure activities and over the previous 24 hours. The level of negative impact of dysmenorrhea on daily life was scored on a 5-point scale (0=Not at all to 4=Extremely impacted). For each of the 3 impact items, the baseline score was to be defined as the mean value obtained from the 2 menstruations during the screening period. The change from baseline to Treatment Cycle 2 in the number of days during the cramping window with no impact of dysmenorrhea (score = 0) on each of the following items was to be presented: work/school, physical activities and leisure/social activities.
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End point type |
Secondary
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End point timeframe |
Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
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| Notes [8] - Study terminated [9] - Study terminated |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Pelvic Pain Score of “0” or “1” and No Use of Ibuprofen Tablets at Treatment Cycle 2 | ||||||||||||
End point description |
Participants were asked to rate their worst pain or cramps on a scale of 0 to 10 (0=No pain or cramps to 10=Extreme pain or cramps) and to indicate the number of ibuprofen tablets they took during the 4-day cramping window. The percentage of participants with no or minimal pelvic pain (score of “0” or “1”) and no use of ibuprofen at Treatment Cycle 2 was to be presented.
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End point type |
Secondary
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End point timeframe |
Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
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| Notes [10] - Study terminated [11] - Study terminated |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With ≥3-point Reduction in Peak Pelvic Pain Score and a Decrease in Number of Ibuprofen Tablets Taken at Treatment Cycle 2, Compared to Baseline | ||||||||||||
End point description |
Participants were asked to rate their worst pain or cramps in the past 24 hours on a scale of 0 to 10 (0=No pain or cramps to 10=Extreme pain or cramps) and to indicate the number of ibuprofen tablets they took during the 4-day cramping window. The baseline peak pelvic pain score and number of ibuprofen tablets taken were to be defined as the mean value of the 2 peak pelvic pain scores and the mean value of the total number of ibuprofen tablets taken during the cramping window of each of the 2 menstruations during the screening period, respectively. The percentage of participants with a reduction in peak pelvic pain score of ≥3 points and a decrease in the use of ibuprofen at Treatment Cycle 2 as compared to baseline was to be presented.
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End point type |
Secondary
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End point timeframe |
Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
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| Notes [12] - Study terminated [13] - Study terminated |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in the Mean Pelvic Pain Score at Treatment Cycle 2 | ||||||||||||
End point description |
The mean pelvic pain score was to be calculated as the mean of the highest scores for pelvic pain observed within the 4-day cramping window of the screening or treatment cycle. The baseline mean pelvic pain score was to be defined as the mean value of the 2 mean pelvic pain scores of the 2 menstruations during the screening period. The change from baseline in mean pelvic pain score at Treatment Cycle 2 was to be presented.
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End point type |
Secondary
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End point timeframe |
Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
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| Notes [14] - Study terminated [15] - Study terminated |
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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 30 days after last dose of study treatment (Up to approximately 126 days)
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Adverse event reporting additional description |
The population consisted of all participants in whom a vaginal ring was inserted.
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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 |
Participants received up to 4 cycles of ENGE2 at a daily dose of 125 μg/300 μg via vaginal ring. Each cycle consisted of 21 days of MK-8342B vaginal ring use followed by 7 ring-free days. | |||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received up to 4 cycles of placebo via vaginal ring. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days. | |||||||||||||||||||||
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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? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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. | |||
| 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 | |||
