A Study to Evaluate the Effect of Contraceptive Vaginal Rings on Primary Dysmenorrhea (P08257/MK-8175A/MK-8342B-057)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Dysmenorrhea

Intervention / Treatment
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* Drug: Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR)
* Drug: Etonogestrel containing contraceptive vaginal ring (ENG-CVR)
* Drug: Placebo
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOMAC-E2 700/300 mcg<br>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. | Drug: Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR)<br>* Either 700 or 900 mcg NOMAC and 300 mcg E2 intravaginal ring for two 28-day cycles<br>* Other names: MK-8175A;Drug: Ibuprofen<br>* 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)<br>* Other names: Motrin;|
| Experimental: NOMAC-E2 900/300 mcg<br>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. | Drug: Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR)<br>* Either 700 or 900 mcg NOMAC and 300 mcg E2 intravaginal ring for two 28-day cycles<br>* Other names: MK-8175A;Drug: Ibuprofen<br>* 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)<br>* Other names: Motrin;|
| Experimental: ENG-E2 100/300 mcg<br>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. | Drug: Etonogestrel containing contraceptive vaginal ring (ENG-CVR)<br>* Either 100 or 125 mcg ENG and 300 mcg E2, intravaginally for two 28-day cycles<br>* Other names: MK-8342B;Drug: Ibuprofen<br>* 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)<br>* Other names: Motrin;|
| Experimental: ENG-E2 125/300 mcg<br>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. | Drug: Etonogestrel containing contraceptive vaginal ring (ENG-CVR)<br>* Either 100 or 125 mcg ENG and 300 mcg E2, intravaginally for two 28-day cycles<br>* Other names: MK-8342B;Drug: Ibuprofen<br>* 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)<br>* Other names: Motrin;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Placebo to match vaginal ring, intravaginally for two 28-day cycles<br>Drug: Ibuprofen<br>* 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)<br>* Other names: Motrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and Day 29 to 56 (Cycle 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and Day 29 to 56 (Cycle 2) | 
| 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. | Baseline and Day 29 to 56 (Cycle 2) | 
| 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. | Baseline and Day 29 to 56 (Cycle 2) |