Trial to Assess MK-8342B Treatment Efficacy-Safety in Dysmenorrhea

• Register: EUCTR
• Last refreshed on: 9 January 2017
• Main ID: EUCTR2015-004326-34-PL
• Date of registration: 25/01/2016
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Trial to Assess MK-8342B Treatment Efficacy-Safety in Dysmenorrhea
• Scientific title: A Phase 3 Randomized, Double-blind, Placebo-Controlled Trial to Study the Efficacy and Safety of MK-8342B (ENG-E2 vaginal ring) in Women with Moderate to Severe Primary Dysmenorrhea.
• Date of first enrolment: 16/03/2016
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004326-34
• 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Chile, Guatemala, Italy, Poland, Puerto Rico, Russian Federation, South Africa, Sweden, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
In order to be eligible for participation in this trial, the subject must:

1. Provide written informed consent/assent for the trial. Provide consent/assent if agreeing to participate in sample collection for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.

2. Be a post-menarcheal female, age =50 years.

3. Have a history of moderate to severe primary dysmenorrhea for the past 3 months or longer, and no history of recurrent non-menstrual pelvic pain intermittently or continuously throughout the month, and no history of dysmenorrhea secondary to structural pelvic pathology (e.g., endometriosis, fibroids, pelvic inflammatory disease, adenomyosis). Subjects with a history of mid-cycle discomfort with ovulation (mittelschmerz) may participate.

4. Have a body mass index (BMI) of =18 and <38 kg/m2.

5. If heterosexually active, agrees to consistently use male condoms as the contraceptive method starting the day of Visit 1, and during the entire treatment period (until 14 days after removal of the last study ring) unless her partner is surgically sterilized. Sporadic use of an emergency contraceptive (EC) is not an exclusion; however, the
investigator should carefully assess subject’s ability to comply with the protocol requirements for condom use.

6. Has a history of regular menstrual cycles with a cycle length between 24 and 32 days (inclusive) for the past three months.

7. Be in good physical and mental health, based upon the medical judgment of the investigator

8. Be able and willing (in the opinion of the investigator) to adhere to use of the vaginal ring and to all required trial procedures, including study visits and use of daily eDiary, and not planning to relocate during the study (such that the subject would not be able to continue participation at the trial site).

9. Be willing to use the rescue medication ibuprofen at the study recommended dose (provided by the study site) and no other pain medication for treatment of dysmenorrhea.

Additional inclusion criteria to be verified at Visit 3:

10. Have demonstrated a menstrual cycle length between 24 and 32 days (inclusive) in the eDiary during the screening period (1st spontaneous menses during screening period (SM1) to 2nd spontaneous menses during screening period (SM2)).

11. Have demonstrated moderate to severe dysmenorrhea during the screening period as defined by a peak menstrual cramping pain score =6 on item #2 of the Dysmenorrhea Daily Diary during both SM1 and SM2.

12. Have no more than 3 days with incomplete eDiary entries during the screening period and no more than one day with incomplete entries during SM2.

13. Have demonstrated compliance with taking only the study provided ibuprofen tablets for dysmenorrhea during SM1 and SM2 as evidence in the eDiary.
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 320
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Has a personal history of VTE (deep vein thrombosis, pulmonary embolism) or history of ATE events (i.e., myocardial infarction, stroke, or peripheral arterial), or history of transient ischemic attack or angina pectoris or claudication.
- Is at a higher risk of VTE events due to recent prolonged immobilization (within 2 weeks prior to screening, e.g., due to trauma, surgery, or other illness markedly limiting mobility, planned surgery limiting mobilization, or has a hereditary or acquired predisposition or elevated risk for venous or arterial thrombosis, such as APC (activated protein C) resistance, antithrombin-III-deficiency, protein C
deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant) or has thrombogenic cardiac valve or rhythm abnormalities of the heart associated with thromboembolism (e.g., atrial fibrillation).
- Is currently smoking or uses tobacco/nicotine containing products and is =35 years of age.
- Has a history of severe dyslipoproteinemia.
- Is <35 years of age and has a history of migraine with aura or focal neurological symptoms; or is =35 years of age and has a history of migraines (with or without aura or focal neurologic symptoms).
- Has diabetes mellitus with end-organ involvement (nephropathy, retinopathy, neuropathy or other vascular involvement) or has had diabetes for >20 years duration.
- Has multiple cardiovascular risk factors such as older age (>35 years), obesity (BMI >30 kg/m2), inadequately controlled hypertension, use of tobacco/ nicotine products, or inadequately controlled diabetes which, in the opinion of the investigator, in composite pose an unacceptable risk of study participation. The investigator should consider the severity of each risk factor in determining whether study participation is appropriate.
- Has a known or suspected pregnancy.
- Has been pregnant or breastfeeding within the past 2 months.
- Has used hormonal contraceptives (pill, patch, ring, implant, intrauterine system) within the past 3 months.
- Current use of non-hormonal intrauterine device (IUD). To qualify, device must be discontinued before V1 and the diagnosis of primary dysmenorrhea must have preceded IUD insertion.
- Within the past 6 months has had undiagnosed (unexplained) abnormal vaginal bleeding or any other abnormal bleeding that is expected to recur during the study (e.g., bleeding from a cervical polyp, recurrent bleeding after intercourse).
- Currently has gonorrhea, chlamydia, or trichomonas or symptomatic vaginitis/cervicitis. Subjects may be rescreened 3 weeks after completing treatment for these conditions.
- Has an abnormal cervical smear or positive high-risk human papilloma virus (HPV) test at screening or documented within 3 years of screening.
- Has Stage 4 pelvic organ prolapse (1 cm beyond introitus) or lesser degrees of prolapse with a history of difficulty retaining tampons, vaginal rings, or other products within the vagina.
- Has a history of pancreatitis associated with severe hypertriglyceridemia.
- Has clinically significant liver disease, including active viral hepatitis or cirrhosis.
Subjects with a prior history of liver disease which is now inactive or successfully treated may be enrolled if liver function values (AST, ALT, total bilirubin) have been normal for the past year and are within the normal range (per central lab) at V1.
- Has history of conditions of the gastrointestinal or u

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

Health Condition(s) or Problem(s) studied

Moderate to severe primary dysmenorrhea
MedDRA version: 19.0 Level: LLT Classification code 10062851 Term: Primary dysmenorrhea System Organ Class: 100000004872
MedDRA version: 19.0 Level: LLT Classification code 10013934 Term: Dysmenorrhea System Organ Class: 100000004872

Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

Intervention(s)

Product Name: ENG-E2 vaginal ring
Product Code: MK-8342B
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: Etonogestrel
CAS Number: 54048-10-1
Current Sponsor code: MK-8342
Other descriptive name: ETONOGESTREL, ENG, or Org 3236
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 125-
INN or Proposed INN: Estradiol
CAS Number: 50-28-2
Current Sponsor code: MK-9271
Other descriptive name: E2, Org 2317
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

Trade Name: Ibuprofen Tablets USP 400 mg
Product Name: Ibuprofen USP 400 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: IBUPROFEN
CAS Number: 15687-27-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The main assessment of the primary endpoint is performed at Treatment cycle 2.

Primary end point(s): The primary endpoint of this study is a composite responder endpoint defined as the proportion of subjects with a reduction in peak pelvic pain score of at least 3 points (item #2 of the Dysmenorrhea Daily Diary, and no increase in the use of rescue pain relief medication (total number of ibuprofen 400 mg tablets taken) at Treatment Cycle 2 as compared to baseline.

Main Objective: In women with moderate to severe primary dysmenorrhea:

1. To evaluate the efficacy of the ENG-E2 vaginal ring relative to placebo in the treatment of dysmenorrhea at Treatment Cycle 2.

2. To assess the safety and tolerability of the ENG-E2 vaginal ring over 4 treatment cycles.

Secondary Objective: In women with moderate to severe primary dysmenorrhea, to assess the effect of treatment with the ENG-E2 vaginal ring relative to placebo at Treatment Cycle 2 on:

1. The change from baseline in the peak pelvic pain score.

2. The number of days with no impact of dysmenorrhea (score = 0) on each of the following DysDD items separately: work/school, physical activities, and social or leisure activities.

3. The proportion of subjects with no or minimal pain (i.e. peak pelvic pain score of “0” or “1”) and no use of ibuprofen tablets.

4. The proportion of subjects with a =3 point reduction in peak pelvic pain score and a decrease in the number of ibuprofen tablets as compared to baseline.

5. The change from baseline in the mean pelvic pain score.

Secondary Outcome(s)

Secondary end point(s): 1. Change from baseline cycle in the peak pelvic pain score.

2. Change from baseline cycle in the number of days with no impact (score = 0) of dysmenorrhea on each of the DysDD items, separately:
physical activities, social or leisure activities, and work/school.

3. Proportion of subjects with pelvic pain score of "0" or "1" and no use of ibuprofen tablets.

4. Proportion of subjects with reduction in peak pelvic pain score of at least 3 points and a decrease in number of ibuprofen tablets taken.

5. Change from baseline cycle in the mean pelvic pain score.

Timepoint(s) of evaluation of this end point: The main assessment of the secondary endpoints are performed at Treatment cycle 2.

Secondary ID(s)

2015-004326-34-SE

MK-8342B-060

Source(s) of Monetary Support

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