Trial Outcomes & Findings for Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in Women With Primary Dysmenorrhea (With Optional Extension) (MK-8342B-059) (NCT NCT02668783)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

25 participants

Primary outcome timeframe

Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant

Results posted on

2024-05-28

Participant Flow

Participant milestones

Participant milestones
Measure	ENG-E2 125 μg/300 μg Participants received 4 (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 ring-free days.	Placebo Participants received 4 (or 6 cycles if also participating in the extension) of placebo. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days.
Overall Study STARTED	13	12
Overall Study Treated	13	11
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	13	12

Reasons for withdrawal

Reasons for withdrawal
Measure	ENG-E2 125 μg/300 μg Participants received 4 (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 ring-free days.	Placebo Participants received 4 (or 6 cycles if also participating in the extension) of placebo. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days.
Overall Study Pregnancy	0	1
Overall Study Protocol Violation	2	1
Overall Study Study terminated by sponsor	9	10
Overall Study Subject moved	1	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in Women With Primary Dysmenorrhea (With Optional Extension) (MK-8342B-059)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ENG-E2 125 μg/300 μg n=13 Participants Participants received 4 (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 ring-free days.	Placebo n=12 Participants Participants received 4 (or 6 cycles if also participating in the extension) of placebo. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days.	Total n=25 Participants Total of all reporting groups
Age, Continuous	27 Years STANDARD_DEVIATION 7 • n=5 Participants	29 Years STANDARD_DEVIATION 6 • n=7 Participants	28 Years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant

Population: Population was to consist of all participants in whom 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, committee to determine cramping windows was not assembled, cramping windows were not determined \& efficacy data could not be analyzed.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to approximately 158 days

Population: All randomized participants in whom a vaginal ring was inserted.

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.

Outcome measures

Outcome measures
Measure	ENG-E2 125 μg/300 μg n=13 Participants Participants received 4 (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 ring-free days.	Placebo n=11 Participants Participants received 4 (or 6 cycles if also participating in the extension) of placebo. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days.
Number of Participants Who Experienced an Adverse Event (AE)	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to approximately 128 days

Population: All randomized participants in whom a vaginal ring was inserted.

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 to an AE is presented.

Outcome measures

Outcome measures
Measure	ENG-E2 125 μg/300 μg n=13 Participants Participants received 4 (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 ring-free days.	Placebo n=11 Participants Participants received 4 (or 6 cycles if also participating in the extension) of placebo. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days.
Number of Participants Who Discontinued Treatment Due to an AE	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant

Population: Population was to consist of all participants in whom a vaginal ring was inserted \& who had ≥1 day of diary entry each within 4-day cramping window during a baseline cycle \& a treatment cycle. Due to termination, committee to determine cramping windows was not assembled, cramping windows were not determined \& efficacy data could not be analyzed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant

Population: 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, committee to determine cramping windows was not assembled, cramping windows were not determined \& efficacy data could not be analyzed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Treatment Cycle 2 4-day cramping window, as determined by committee for each participant

Population: 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 Treatment Cycle 2. Due to termination, committee to determine cramping windows was not assembled, cramping windows were not determined \& efficacy data could not be analyzed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant

Population: 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, committee to determine cramping windows was not assembled, cramping windows were not determined \& efficacy data could not be analyzed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant

Population: 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, committee to determine cramping windows was not assembled, cramping windows were not determined \& efficacy data could not be analyzed.

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.

Outcome measures

Outcome data not reported

Adverse Events

ENG-E2 125 Microgram/300 Microgram

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	ENG-E2 125 Microgram/300 Microgram n=13 participants at risk Participants received 4 (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg. Each cycle consisted of 21 days of vaginal ring use followed by 7 ring-free days.	Placebo n=11 participants at risk Participants received 4 (or 6 cycles if also participating in the extension) of placebo. Each cycle consisted of 21 days of placebo vaginal ring use followed by 7 ring-free days.
Pregnancy, puerperium and perinatal conditions Vomiting in pregnancy	0.00% 0/13 • Up to approximately 158 days All randomized participants in whom a vaginal ring was inserted.	9.1% 1/11 • Number of events 1 • Up to approximately 158 days All randomized participants in whom a vaginal ring was inserted.
Psychiatric disorders Mood swings	7.7% 1/13 • Number of events 1 • Up to approximately 158 days All randomized participants in whom a vaginal ring was inserted.	0.00% 0/11 • Up to approximately 158 days All randomized participants in whom a vaginal ring was inserted.
Reproductive system and breast disorders Vulvovaginal discomfort	0.00% 0/13 • Up to approximately 158 days All randomized participants in whom a vaginal ring was inserted.	9.1% 1/11 • Number of events 1 • Up to approximately 158 days All randomized participants in whom a vaginal ring was inserted.

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