Back to resultsA Study to Evaluate the Effect of Contraceptive Vaginal Rings on Primary Dysmenorrhea (P08257/MK-8175A/MK-8342B-057)
Primary Purpose
Dysmenorrhea
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR)
Etonogestrel containing contraceptive vaginal ring (ENG-CVR)
Placebo
Ibuprofen
Sponsored by
About this trial
This is an interventional treatment trial for Dysmenorrhea
Eligibility Criteria
Inclusion Criteria:
- Body mass index (BMI) ≥18 and ≤35
- Established diagnosis of primary dysmenorrhea
- If of child-bearing potential must agree to use condoms for contraception during the entire screening period, treatment period, and post-treatment period until the final study visit, unless she or her partner are surgically sterilized
- Agree to stop using hormonal contraceptive (combined or progestin-only), or a non hormonal intrauterine device (IUD)
- Regular menstrual cycles ranging from 24 to 35 days in length
Exclusion Criteria:
- Any of the following contraindications to the use of contraceptive steroids including: presence or a history of venous or arterial thrombotic/thromboembolic events or cerebrovascular accident (stroke, history of migraine with focal neurological symptoms, diabetes mellitus with vascular involvement, severe or multiple risk factor(s) for venous or arterial thrombosis, severe dyslipoproteinemia, severe hypertension, pancreatitis or a history thereof if associated with severe hypertriglyceridaemia, presence or history of severe hepatic (liver) disease, including benign or malignant tumors, known or suspected sex steroid-influenced malignancies, and/or undiagnosed vaginal bleeding
- Pregnant or breastfeeding
- Secondary dysmenorrhea
- Has not had spontaneous menstruation following a delivery or abortion
- Participated in an investigational drug study within 30 days
- History of malignancy ≤5 years
- Documented abnormal cervical smear result within 6 months
- Use of recreational or illicit drugs
- Consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking
- Allergy/sensitivity to ibuprofen, or any contraindication to its use, or has experienced asthma, urticaria, or allergic-type reactions after taking aspirin, or other nonsteroidal anti inflammatory drugs
- Has been sterilized using a fallopian tube occlusion device
- Is receiving, or has received sex hormones for any purpose other than contraception within 2 months or injectable hormonal contraception within 6 months
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
NOMAC-E2 700/300 mcg
NOMAC-E2 900/300 mcg
ENG-E2 100/300 mcg
ENG-E2 125/300 mcg
Placebo
Arm Description
NOMAC-E2 700/300 mcg will be 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 will be 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 will be 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 will be 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 will be 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.
Outcomes
Primary Outcome Measures
Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2
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).
Secondary Outcome Measures
Change From Baseline in Total Mean Impact Score Through Cycle 2
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).
Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2
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.
Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01670656
Brief Title
A Study to Evaluate the Effect of Contraceptive Vaginal Rings on Primary Dysmenorrhea (P08257/MK-8175A/MK-8342B-057)
Official Title
A Multicenter, Randomized, Partially Blinded, Placebo-controlled Clinical Trial to Evaluate the Effect on Primary Dysmenorrhea of Vaginal Rings With an Average Daily Release of 700 μg Nomegestrol Acetate (NOMAC) and 300 μg Estradiol (E2), or 900 μg Nomegestrol Acetate (NOMAC) and 300 μg Estradiol (E2), or 100 μg Etonogestrel (ENG) and 300 μg E2, or 125 μg Etonogestrel (ENG) and 300 μg E2. Protocol MK-8175A/MK-8342B 057 (Abbreviated as P057), Also Known as SCH900121/SCH900432 08257 (Abbreviated as P08257)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 21, 2013 (Actual)
Primary Completion Date
September 11, 2013 (Actual)
Study Completion Date
September 12, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organon and Co
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study investigates four vaginal ring groups with respect to relief of primary dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant treatment efficacy in relief of primary dysmenorrhea.
Detailed Description
The study investigates four vaginal ring groups with respect to relief of primary dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant treatment efficacy in relief of primary dysmenorrhea. The intake of ibuprofen rescue medication and the impact on daily life is investigated: change from baseline data of these two variables will be compared between each of the four active ring groups, separately, and the placebo ring group. Furthermore, the study assesses the measurement characteristics and psychometric properties of a newly developed Dysmenorrhea Daily Dairy. Vaginal bleeding pattern and general safety and tolerability will also be evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dysmenorrhea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
439 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NOMAC-E2 700/300 mcg
Arm Type
Experimental
Arm Description
NOMAC-E2 700/300 mcg will be 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.
Arm Title
NOMAC-E2 900/300 mcg
Arm Type
Experimental
Arm Description
NOMAC-E2 900/300 mcg will be 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.
Arm Title
ENG-E2 100/300 mcg
Arm Type
Experimental
Arm Description
ENG-E2 100/300 mcg will be 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.
Arm Title
ENG-E2 125/300 mcg
Arm Type
Experimental
Arm Description
ENG-E2 125/300 mcg will be 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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be 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.
Intervention Type
Drug
Intervention Name(s)
Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR)
Other Intervention Name(s)
SCH900121, MK-8175A
Intervention Description
Either 700 or 900 mcg NOMAC and 300 mcg E2 intravaginal ring for two 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Etonogestrel containing contraceptive vaginal ring (ENG-CVR)
Other Intervention Name(s)
SCH900432, MK-8342B
Intervention Description
Either 100 or 125 mcg ENG and 300 mcg E2, intravaginally for two 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to match vaginal ring, intravaginally for two 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
Motrin
Intervention Description
Ibuprofen 400 mg will be dispensed throughout the entire study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose is 3200 mg (8 tablets)
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2
Description
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).
Time Frame
Baseline and Day 29 to 56 (Cycle 2)
Secondary Outcome Measure Information:
Title
Change From Baseline in Total Mean Impact Score Through Cycle 2
Description
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).
Time Frame
Baseline and Day 29 to 56 (Cycle 2)
Title
Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2
Description
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.
Time Frame
Baseline and Day 29 to 56 (Cycle 2)
Title
Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2
Description
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.
Time Frame
Baseline and Day 29 to 56 (Cycle 2)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Body mass index (BMI) ≥18 and ≤35
Established diagnosis of primary dysmenorrhea
If of child-bearing potential must agree to use condoms for contraception during the entire screening period, treatment period, and post-treatment period until the final study visit, unless she or her partner are surgically sterilized
Agree to stop using hormonal contraceptive (combined or progestin-only), or a non hormonal intrauterine device (IUD)
Regular menstrual cycles ranging from 24 to 35 days in length
Exclusion Criteria:
Any of the following contraindications to the use of contraceptive steroids including: presence or a history of venous or arterial thrombotic/thromboembolic events or cerebrovascular accident (stroke, history of migraine with focal neurological symptoms, diabetes mellitus with vascular involvement, severe or multiple risk factor(s) for venous or arterial thrombosis, severe dyslipoproteinemia, severe hypertension, pancreatitis or a history thereof if associated with severe hypertriglyceridaemia, presence or history of severe hepatic (liver) disease, including benign or malignant tumors, known or suspected sex steroid-influenced malignancies, and/or undiagnosed vaginal bleeding
Pregnant or breastfeeding
Secondary dysmenorrhea
Has not had spontaneous menstruation following a delivery or abortion
Participated in an investigational drug study within 30 days
History of malignancy ≤5 years
Documented abnormal cervical smear result within 6 months
Use of recreational or illicit drugs
Consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking
Allergy/sensitivity to ibuprofen, or any contraindication to its use, or has experienced asthma, urticaria, or allergic-type reactions after taking aspirin, or other nonsteroidal anti inflammatory drugs
Has been sterilized using a fallopian tube occlusion device
Is receiving, or has received sex hormones for any purpose other than contraception within 2 months or injectable hormonal contraception within 6 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
30439359
Citation
Fox MC, Klipping C, Nguyen AM, Frenkl TL, Cruz SM, Wang Y, Korver T. A phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of vaginal rings containing nomegestrol acetate or etonogestrel and 17beta-estradiol in the treatment of women with primary dysmenorrhea. Contraception. 2019 Feb;99(2):125-130. doi: 10.1016/j.contraception.2018.10.009. Epub 2018 Nov 12.
Results Reference
derived
Learn more about this trial
A Study to Evaluate the Effect of Contraceptive Vaginal Rings on Primary Dysmenorrhea (P08257/MK-8175A/MK-8342B-057)
We'll reach out to this number within 24 hrs