Trial Outcomes & Findings for A Study to Evaluate the Effect of Contraceptive Vaginal Rings on Primary Dysmenorrhea (P08257/MK-8175A/MK-8342B-057) (NCT NCT01670656)
NCT ID: NCT01670656
Last Updated: 2024-05-28
Results Overview
The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: "Cramps") in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
439 participants
Primary outcome timeframe
Baseline and Day 29 to 56 (Cycle 2)
Results posted on
2024-05-28
Participant Flow
Participant milestones
| Measure |
NOMAC-E2 700/300 mcg
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
NOMAC-E2 900/300 mcg
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 100/300 mcg
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 125/300 mcg
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
86
|
91
|
87
|
85
|
90
|
|
Overall Study
Treated
|
86
|
91
|
86
|
85
|
90
|
|
Overall Study
COMPLETED
|
83
|
84
|
79
|
79
|
79
|
|
Overall Study
NOT COMPLETED
|
3
|
7
|
8
|
6
|
11
|
Reasons for withdrawal
| Measure |
NOMAC-E2 700/300 mcg
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
NOMAC-E2 900/300 mcg
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 100/300 mcg
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 125/300 mcg
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Overall Study
Non-compliance with study drug
|
0
|
0
|
3
|
0
|
1
|
|
Overall Study
Pregnancy
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
0
|
|
Overall Study
Non-compliance with protocol
|
0
|
3
|
1
|
1
|
2
|
|
Overall Study
Adverse Event
|
2
|
2
|
2
|
3
|
3
|
|
Overall Study
Subject withdrew consent
|
0
|
1
|
2
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
0
|
3
|
|
Overall Study
Subject moved
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study to Evaluate the Effect of Contraceptive Vaginal Rings on Primary Dysmenorrhea (P08257/MK-8175A/MK-8342B-057)
Baseline characteristics by cohort
| Measure |
NOMAC-E2 700/300 mcg
n=86 Participants
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
NOMAC-E2 900/300 mcg
n=91 Participants
NOMAC-E2 900/300 mcg administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 100/300 mcg
n=87 Participants
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 125/300 mcg
n=85 Participants
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
n=90 Participants
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Total
n=439 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
28.7 Years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
28.7 Years
STANDARD_DEVIATION 8.1 • n=7 Participants
|
29.0 Years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
28.3 Years
STANDARD_DEVIATION 7.8 • n=4 Participants
|
28.4 Years
STANDARD_DEVIATION 8.2 • n=21 Participants
|
28.6 Years
STANDARD_DEVIATION 7.8 • n=10 Participants
|
|
Sex: Female, Male
Female
|
86 Participants
n=5 Participants
|
91 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
90 Participants
n=21 Participants
|
439 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 29 to 56 (Cycle 2)Population: All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Menstrual Cramping Pain Score
The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: "Cramps") in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe).
Outcome measures
| Measure |
NOMAC-E2 700/300 mcg
n=85 Participants
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
NOMAC-E2 900/300 mcg
n=91 Participants
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 100/300 mcg
n=86 Participants
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 125/300 mcg
n=85 Participants
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
n=90 Participants
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2
|
-1.7 Units on a scale
Interval -2.0 to -1.5
|
-1.7 Units on a scale
Interval -1.9 to -1.5
|
-1.9 Units on a scale
Interval -2.1 to -1.7
|
-1.7 Units on a scale
Interval -1.9 to -1.5
|
-1.2 Units on a scale
Interval -1.4 to -0.9
|
SECONDARY outcome
Timeframe: Baseline and Day 29 to 56 (Cycle 2)Population: All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Total Mean Impact Score
Total Mean Impact Score is the mean of the sum of the daily responses to questions 6, 8, 9, and 10 in the Dysmenorrhea Daily e-Dairy, as recorded within the menstrual cramping pain analysis window. These questions assessed how much interference there was from pelvic cramping pain on work/school activities (Q6), physical activities (Q8), social/leisure activities (Q9) and sleep (Q10). Each question was rated on a 5-point (0-4) scale, with 0 being "not at all", 1 "slightly", 2 "moderately", 3 "quite a bit" and 4 "extremely". The total mean impact score could thus range from 0 (lowest possible impact) to 16 (highest possible impact).
Outcome measures
| Measure |
NOMAC-E2 700/300 mcg
n=85 Participants
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
NOMAC-E2 900/300 mcg
n=90 Participants
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 100/300 mcg
n=86 Participants
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 125/300 mcg
n=85 Participants
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
n=90 Participants
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Change From Baseline in Total Mean Impact Score Through Cycle 2
|
-4.8 Units on a scale
Interval -5.6 to -4.0
|
-5.0 Units on a scale
Interval -5.7 to -4.2
|
-4.7 Units on a scale
Interval -5.5 to -3.9
|
-4.3 Units on a scale
Interval -5.1 to -3.5
|
-3.1 Units on a scale
Interval -3.9 to -2.4
|
SECONDARY outcome
Timeframe: Baseline and Day 29 to 56 (Cycle 2)Population: All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Ibuprofen Tablets Taken
Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.
Outcome measures
| Measure |
NOMAC-E2 700/300 mcg
n=85 Participants
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
NOMAC-E2 900/300 mcg
n=91 Participants
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 100/300 mcg
n=86 Participants
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 125/300 mcg
n=85 Participants
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
n=90 Participants
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2
|
-6.4 Ibuprofen tablets
Interval -7.5 to -5.3
|
-6.3 Ibuprofen tablets
Interval -7.4 to -5.2
|
-7.1 Ibuprofen tablets
Interval -8.2 to -6.0
|
-6.0 Ibuprofen tablets
Interval -7.1 to -4.9
|
-4.8 Ibuprofen tablets
Interval -6.0 to -3.7
|
SECONDARY outcome
Timeframe: Baseline and Day 29 to 56 (Cycle 2)Population: All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Days of Ibuprofen Intake
Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.
Outcome measures
| Measure |
NOMAC-E2 700/300 mcg
n=85 Participants
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
NOMAC-E2 900/300 mcg
n=91 Participants
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 100/300 mcg
n=86 Participants
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 125/300 mcg
n=85 Participants
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
n=90 Participants
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2
|
-1.3 Days of ibuprofen intake
Interval -1.5 to -1.0
|
-1.7 Days of ibuprofen intake
Interval -2.0 to -1.4
|
-1.7 Days of ibuprofen intake
Interval -2.0 to -1.4
|
-1.4 Days of ibuprofen intake
Interval -1.7 to -1.1
|
-1.1 Days of ibuprofen intake
Interval -1.4 to -0.9
|
Adverse Events
NOMAC-E2 (700/300 mcg)
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
NOMAC-E2 (900/300 mcg)
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
ENG-E2 (100/300 mcg)
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
ENG-E2 (125/300 mcg)
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
NOMAC-E2 (700/300 mcg)
n=86 participants at risk
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days
|
NOMAC-E2 (900/300 mcg)
n=91 participants at risk
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 (100/300 mcg)
n=86 participants at risk
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 (125/300 mcg)
n=85 participants at risk
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
n=90 participants at risk
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Infections and infestations
Appendicitis
|
0.00%
0/86 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/91 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/86 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.2%
1/85 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/90 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/86 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.1%
1/91 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/86 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/85 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/90 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
|
Psychiatric disorders
Impulse-control disorder
|
0.00%
0/86 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.1%
1/91 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/86 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/85 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
0.00%
0/90 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
Other adverse events
| Measure |
NOMAC-E2 (700/300 mcg)
n=86 participants at risk
NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days
|
NOMAC-E2 (900/300 mcg)
n=91 participants at risk
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 (100/300 mcg)
n=86 participants at risk
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
ENG-E2 (125/300 mcg)
n=85 participants at risk
ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
Placebo
n=90 participants at risk
Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
10.5%
9/86 • Number of events 13 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
9.9%
9/91 • Number of events 19 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
12.8%
11/86 • Number of events 13 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
5.9%
5/85 • Number of events 7 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
7.8%
7/90 • Number of events 9 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
|
Reproductive system and breast disorders
Breast pain
|
5.8%
5/86 • Number of events 7 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.1%
1/91 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.2%
1/86 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.2%
1/85 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
2.2%
2/90 • Number of events 3 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
|
Skin and subcutaneous tissue disorders
Acne
|
1.2%
1/86 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.1%
1/91 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
2.3%
2/86 • Number of events 2 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
1.2%
1/85 • Number of events 1 • Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
|
5.6%
5/90 • Number of events 7 • Up to 64 days
The Safety Analysis was based on 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 investigator agrees to provide to the Sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including slides and texts of oral or other public presentations and texts of any transmission through any electronic media that report results of the trial. The Sponsor has the right to review and comment with respect to publications, abstracts, slides, and manuscripts, as wells as comment on the data analysis and presentation.
- Publication restrictions are in place
Restriction type: OTHER