Vaginal ring dysmenorrhea feasibility trial.

• Register: EUCTR
• Last refreshed on: 18 November 2013
• Main ID: EUCTR2012-002449-40-NL
• Date of registration: 05/09/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Vaginal ring dysmenorrhea feasibility trial.
• Scientific title: A multicenter, randomized, partially blinded, placebo-controlled clinical trial to evaluate the effect on primary dysmenorrheal 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
• Date of first enrolment: 22/10/2012
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002449-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Austria, Belgium, Chile, Colombia, Denmark, Germany, Mexico, Netherlands, New Zealand, Norway, Poland, South Africa, Spain, Sweden

Contacts

• Name: Tjeerd Korver, PhD
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Tjeerd Korver, PhD
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject must be willing and able to provide written informed consent for the trial.
2. Subject must be female.
3. Subject must be ?18 to ?50 years of age.
4. Subject must have a body mass index (BMI) =18 and =35.
5. Subject must have an established diagnosis of primary dysmenorrhea, characterized by menstrual pain in the absence of detectable pelvic pathology (eg, endometriosis, fibroids, pelvic inflammatory disease).
6. Each non-sterilized sexually active subject 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.
7. Subject using a hormonal contraceptive (combined or progestin-only), or a non-hormonal IUD, at the screening visit must agree to stop using that method.
8. Subject has regular menstrual cycles ranging from 24 to 32 days in length (to be confirmed at the randomization visit following completion of a baseline menstrual cycle).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 450
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subject has any contraindication to the use of contraceptive steroids.
2. Subject has secondary dysmenorrhea – ie, menstrual pain in the presence of detectable pelvic pathology (eg, endometriosis, fibroids, pelvic inflammatory disease).
3. Subject has not had spontaneous menstruation following a delivery or abortion at the screening visit.
4. The subject is breastfeeding or has not had spontaneous menstruation following completion of breastfeeding at the screening visit.
5. Subject has a history of malignancy =5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
6. Subject had a documented abnormal cervical smear result within 6 months prior to the screening visit.
7. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Reproductive physiologi cal processes [G08]

This study will investigate the use of 4 doses of combined contraceptives (a progestin with an estrogen) in a vaginal ring dosage form for the treatment of dysmenorrhea (menstrual cramping pain). A placebo control arm will also be utilized.
MedDRA version: 15.0 Level: LLT Classification code 10013934 Term: Dysmenorrhea System Organ Class: 10038604 - Reproductive system and breast disorders

Intervention(s)

Product Name: PR1 - NOMAC-E2
Product Code: MK-8175A SCH 900121
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: NOMEGESTROL ACETATE
CAS Number: 58652-20-3
Current Sponsor code: Org 10486-0, SCH 900175, MK8175
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 700-
INN or Proposed INN: ESTRADIOL
CAS Number: 50-28-2
Current Sponsor code: Org 2317, SCH900618, MK9271
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Vaginal delivery system
Route of administration of the placebo: Vaginal use

Product Name: PR2 - NOMAC-E2
Product Code: MK-8175A SCH 900121
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: NOMEGESTROL ACETATE
CAS Number: 58652-20-3
Current Sponsor code: Org 10486-0, SCH 900175, MK-8175
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 900-
INN or Proposed INN: ESTRADIOL
CAS Number: 50-28-2
Current Sponsor code: Org 2317, SCH900618, MK9271
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Vaginal delivery system
Route of administration of the placebo: Vaginal use

Product Name: PR3 - ENG + E2
Product Code: MK-8342B / SCH 900432
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: ETONOGESTREL
CAS Number: 54048-10-1
Current Sponsor code: Org 3236, SCH900342, MK8342
Concentration unit: µg/kg microgram(s)/kilogram
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: ESTRADIOL
CAS Number: 50-28-2
Current Sponsor code: Org 2317, SCH900618, MK9271
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Vaginal delivery system
Route of administration of the placebo: Vaginal use

Product Name: PR4 - ENG + E2
Product Code: MK-8342B / SCH 900432
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: ETONOGE

Primary Outcome(s)

Primary end point(s): Change from baseline at the end of the study in menstrual cramping pain

Main Objective: To identify at least one dose of progestin/estrogen amongst the 4 active doses being tested, administered as a vaginal ring, that shows clinically relevant treatment efficacy in relief of primary dysmenorrhea, as demonstrated by a statistically significantly larger reduction (as compared to baseline) in mean menstrual cramping pain score compared to placebo.

Secondary Objective: In subjects with primary dysmenorrhea:
• To evaluate the treatment efficacy based on the intake of ibuprofen rescue medication and impact on daily life, as compared to baseline
• To assess the measurement characteristics and psychometric properties of the newly developed Dysmenorrhea Daily Diary, including a determination of the minimally-important difference in pelvic pain, as compared to baseline
• To evaluate the vaginal bleeding pattern associated with treatment
• To evaluate the general safety and tolerability of treatment

Timepoint(s) of evaluation of this end point: At the end of the study, following 2 treatment cycles.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At the end of the study, following 2 treatment cycles.

Secondary end point(s): Change in total mean impact score from baseline through Treatment Cycle 2 (the mean of the sum of daily responses to questions 5, 7, 8, and 9) in the Dysmenorrhea Daily Diary; Change from baseline in total number of ibuprofen tablets taken; and Change from baseline in number of days of ibuprofen intake will be analyzed in the same manner as the primary variable.

Secondary ID(s)

2012-002449-40-DE

P057-00

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.