A multi-center, open-label, randomized, controlled, parallel-group study to assess efficacy and safety of an extended flexible regimen of the combined oral contraceptive SH T00186D (0.02 mg ethinylestradiol as beta-cyclodextrin clathrate and 3 mg drospirenone) compared to the conventional regimen of SH T00186D in the treatment of primary dysmenorrhea - SH T00186 in the treatment of primary dysmenorrhea

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2006-004899-13-GB
• Date of registration: 14/07/2008
• Prospective Registration: Yes
• Primary sponsor: Bayer Schering Pharma AG
• Public title: A multi-center, open-label, randomized, controlled, parallel-group study to assess efficacy and safety of an extended flexible regimen of the combined oral contraceptive SH T00186D (0.02 mg ethinylestradiol as beta-cyclodextrin clathrate and 3 mg drospirenone) compared to the conventional regimen of SH T00186D in the treatment of primary dysmenorrhea - SH T00186 in the treatment of primary dysmenorrhea
• Scientific title: A multi-center, open-label, randomized, controlled, parallel-group study to assess efficacy and safety of an extended flexible regimen of the combined oral contraceptive SH T00186D (0.02 mg ethinylestradiol as beta-cyclodextrin clathrate and 3 mg drospirenone) compared to the conventional regimen of SH T00186D in the treatment of primary dysmenorrhea - SH T00186 in the treatment of primary dysmenorrhea
• Date of first enrolment: 08/08/2008
• Target sample size: 216
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004899-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Medical history of moderate to severe primary dysmenorrhea (i.e., moderate to severe menstruation-related pelvic pain in at least 4 out of 6 preceding cycles)
2. Prospective self-rated sum pain score of >/= 8 over the 2 baseline cycles
3. Age between 18 and 40 years (inclusive) with smoking habits regulated as follows
- Between 18 and 30 years of age, daily cigarette consumption not above 10
- Above 30 years of age, no smoking
4. Non-suspicious cervical smear taken at Visit 1 or within the last 3 months before Visit 1
5. Signed and dated informed consent.

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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Current signs or history of any forms of secondary dysmenorrhea (e.g., due to underlying endometriosis, fibroids, adenomyosis of the uterus, hematometra)
2. Any concomitant disease or condition that requires any intake of analgesic medication
3. Occurrence of less than six menstrual cycles before Visit 1 following delivery, abortion, or lactation
4. Known hypersensitivity to any ingredient of the study drug and/or rescue medication
5. Any known diseases or conditions that compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study medication
6. Any known severe systemic disease that might interfere with the conduct of the study or the interpretation of the results
7. Known uncontrolled thyroid disorders
8. Clinically significant depression (current or in the last year)
9. Any known abnormal clinically significant findings which, according to the assessment of the investigator, may worsen under hormonal treatment
10. Laboratory values outside inclusion range at Screening
11. Participation in another clinical study or administration of an IMP within 1 month prior to study entry (Visit 1) (or 6 months in case of long-acting progestins)
12. Surgeries scheduled in the study period
13. Known liver diseases:
Previous, acute and chronic progressive liver diseases, e.g., disturbances of bilirubin excretion in the bile (Dubin-Johnson and Rotor syndromes), disturbances of bile secretion, disturbances of bile flow (cholestasis, also a history thereof), idiopathic icterus or pruritus during a former pregnancy or estrogen-progestin treatment
Between the subsidence of a viral hepatitis (normalization of liver parameters) and the beginning of the study there must be an interval of at least 6 months.
Previous or current liver tumors
14. Known vascular diseases:
Existing or previous venous thromboembolic diseases (deep vein thrombosis, pulmonary embolism), existing or previous arterial thromboembolic diseases (myocardial infarction, stroke), as well as any condition increasing the disposition to any of the above, e.g., coagulation disorders with tendency to blood clot formation, hereditary anti-thrombin III deficiency, protein-C and/or protein-S deficiency, any venous thromboembolic event occurred in a sibling or a parent at an early age (Uncontrolled arterial hypertension (confirmed systolic blood pressure > 140 mmHg and/or confirmed diastolic blood pressure > 90 mmHg).
Known diabetes mellitus, impaired glucose tolerance
Known disturbances of lipid metabolism
15. Known sickle-cell anemia
16. Known or suspected malignant or premalignant disease, in particular steroid-hormone dependent malignant or premalignant diseases (e.g., endometrial cancer, ovarian cancer, breast cancer), also a history thereof
17. Known other diseases:
Pemphigoid gestationis during a previous pregnancy, middle-ear deafness (otosclerosis), endometrial hyperplasia, migraine with neurological symptoms (complicated migraine), genital bleeding of unknown origin, manifest kidney disease with impaired renal function, porphyria, past or current uterus myomatosus, worsening of chronic bowel disease (Crohn’s disease or ulcerative colitis) under hormonal treatment
18. Known alcohol, drug, or medicine abuse
19. Prohibited concomi

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

Health Condition(s) or Problem(s) studied

women suffering from primary dysmenorrhea
MedDRA version: 9.1 Level: LLT Classification code 10036689 Term: Primary dysmenorrhoea

Intervention(s)

Trade Name: Yaz
Product Name: Yaz flex
Product Code: SH T00186D
Pharmaceutical Form: Tablet
INN or Proposed INN: drospirenone
CAS Number: 67392-87-4
Current Sponsor code: ZK30595
Concentration unit: IU/mg international unit(s)/milligram
Concentration type: equal
Concentration number: 3.0-
INN or Proposed INN: ethinylestradiol as betadex clathrate
CAS Number: 256463-26-0
Current Sponsor code: ZK227269
Concentration unit: IU/mg international unit(s)/milligram
Concentration type: equal
Concentration number: 0.020-

Trade Name: Yaz
Product Name: Yaz
Product Code: SH T00186D
Pharmaceutical Form: Tablet
INN or Proposed INN: drospirenone
CAS Number: 67392-87-4
Current Sponsor code: ZK30595
Concentration unit: IU/mg international unit(s)/milligram
Concentration type: equal
Concentration number: 3.0-
INN or Proposed INN: ethinylestradiol as betadex clathrate
CAS Number: 256463-26-0
Current Sponsor code: ZK227269
Concentration unit: IU/mg international unit(s)/milligram
Concentration type: equal
Concentration number: 0.020-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Secondary efficacy variables:
• Number of days with at least moderate dysmenorrheic pain over 140 days of treatment
• Number of days with pelvic pain (independent of occurrence of vaginal bleeding) over 140 days of treatment
• Number of days with dysmenorrheic pain associated with withdrawal bleedings over 140 days of treatment
• Number of days with dysmenorrheic pain associated with unscheduled bleedings over 140 days of treatment
• Use of rescue medication (standardized intake of ibuprofen)
• Interference with daily activity
• Bleeding patterns
• Investigator assessment of total improvement of primary dysmenorrhea by Clinical Global Impression (CGI) scale
• Subjective assessment of treatment by the patient

Primary end point(s): Primary efficacy variables:
• Number of days with dysmenorrheic pain over 140 days of treatment
It is assumed, that the primary variable is equally distributed in both treatment groups with an at least approximately normal distribution.
Let µt denote the mean number of days with dysmenorrheic pain during 140 days of treatment with an extended flexible regimen of SH T 00186 D, and µp denote the mean number of days with dysmenorrheic pain with the conventional regimen (24 + 4 days) of SH T00186D.For the primary target variable, the hypothesis
H0: | µt - µp | = 0
will be tested against the alternative hypothesis
H1: | µt - µp | > 0 at a 2-sided level of significance of alpha = 0.05.

Main Objective: To evaluate efficacy and safety of the combined oral contraceptive [COC] SH T00186D (0.02 mg ethinylestradiol [EE]; 3 mg drospirenone [DRSP]) applied in a conventional and an extended flexible regimen in the treatment of moderate to severe primary dysmenorrhea
Primary efficacy variables:
• Number of days with dysmenorrheic pain over 140 days of treatment

Secondary ID(s)

310882

2006-004899-13-DE