Hormone withdrawal associated symptoms of headache and pelvic pain suffered by patients receiving LNG containing oral contraception. MedDRA version: 9.1 Level: LLT Classification code 10030970 Term: Oral contraception
Conditions
Interventions
Product Name: SH T00658ID
Product Code: SH T 00658 EA
Pharmaceutical Form: Capsule*
INN or Proposed INN: ESTRADIOL VALERATE
CAS Number: 979328
Current Sponsor code: ZK 5104
Concentration unit: mg mill
Sponsors
Bayer HealthCare AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent 2. Age between 18 and 50 years (inclusive) at visit 1, for smokers up to 35 years (inclusive) 3. Otherwise healthy female subjects requesting contraception and currently using an LNG, GSD or DSG containing OC in a 21-day regimen for at least 3 cycles before visit 1 and suffering from at least moderate pelvic pain, headache or both defined by an average value of = 35 mm for the 3 highest VAS values during cycle days 22-28. 4. Normal or clinically insignificant cervical smear not requiring further follow-up (a cervical smear has to be taken at the screening visit or a normal result has to be documented that was obtained within the last 6 months before screening). Subjects with atypic squamous or glandular cells of undetermined significance (ASCUS) can be included if they have a negative human papilloma virus (HPV) test result. 5. Able to tolerate ibuprofen and willing to use only ibuprofen supplied for the study. 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
Exclusion criteria: 1. Pregnancy or lactation (delivery, abortion, or lactation within less than three cycles before the start of treatment) 2. Body mass index (BMI) > 32 kg/m2 3. Hypersensitivity to any of the study drug ingredients 4. Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study medication (such as but not limited to duodenal ulcers, gastritis, gastrectomy or gastric resection surgery, or renal compromise) 5. Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results 6. Any disease or condition that may worsen under hormonal treatment such as: Cardiovascular • presence or a history of venous or arterial thrombotic / thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident, including prodromi (e.g. transient ischemic attack, angina pectoris) and conditions which could increase the risk of suffering from any of the above mentioned disorders, e.g. a family history indicating a hereditary predisposition • repeated measurements of systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg Liver • presence or history of liver tumors (benign or malignant) • presence or history of severe hepatic disease as long as liver function values have not returned to normal • jaundice and / or pruritus related to cholestasis (Gilbert’s syndrome excepted) • history of cholestatic jaundice associated with pregnancy or previous COC use Metabolic diseases • uncontrolled diabetes mellitus and/or diabetes mellitus with vascular involvement • severe dyslipoproteinemia Other diseases • malignant or premalignant disease • uncontrolled thyroid disorder • chronic inflammatory bowel disease • severe renal insufficiency or acute renal failure • hemolytic uremic syndrome • sickle cell anemia • porphyria • history of hypertriglyceridemia-associated pancreatitis • systemic lupus erythematosus, pemphigoid gestationis during a previous pregnancy • Sydenham chorea • history of herpes gestationis • otosclerosis-related hearing loss • history of migraine with focal neurologic symptoms • epilepsy • clinically significant depression • hereditary angioedema 7. Undiagnosed abnormal genital bleeding 8. Abuse of alcohol, drugs, or medicines (e.g. laxatives) 9. Other contraceptive methods: • sterilization • oral, vaginal or transdermal hormonal contraception during treatment • intra-uterine devices (IUD) with or without hormone release still in place within 30 days of visit 1 • implants/depots still in place within 30 days of visit 1 • long acting preparations (e.g. depot medroxyprogesterone acetate, monthly contraceptive injection) within a period of three times of the injection interval before start of treatment. 10. Any medication that could result in excessive accumulation, impaired metabolism, or altered excretion of the study drug or interfere with the conduct of the study or the interpretation of the results such as: • products containing St. John’s wort (Hypericum perforatum) within 28 days before start of treatment • antibiotics within nine days before start of treatment • anticoagulants (e.g. heparin, coumarin) within 28 days before start of treatment • antiepileptics (hydantoin derivatives [e.g. phenytoin] or carboxamide derivatives [e.g. carbamazepine, oxcarbamazepine], others [e.g.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show superiority to Microgynon with regard to the change in the average of the 3 highest VAS values of the hormone withdrawal associated symptoms headache and pelvic pain on cycle days 22-28 from baseline to cycle 6 in approximately 440 women;Secondary Objective: The secondary objectives of this study are to show superiority to Microgynon with regard to • rescue medication consumption, baseline to cycle 6 • frequency and intensity of other hormone-related symptoms (bloating or swelling, breast tenderness, and nausea or vomiting) during cycle days 22 to 28, baseline to cycle 6 • prevalence of individual hormone-related symptoms during cycle days 1 to 21, baseline to cycle 6 • prevalence of individual hormone-related symptoms during hormone-free interval, i.e. cycle days 27+28 for EV/DNG capsules and cycle days 22 to 28 for the comparator • change in the average of the 3 highest VAS values of the hormone withdrawal associated symptoms pelvic pain or headache during cycle days 22 to 28 from baseline to cycle 3 • bleeding pattern and cycle control • QoL Questionnaires: Psychological General Well-Being Index (PGWBI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Clinical Global Index (CGI).;Primary end point(s): The primary efficacy variable is the individual change of pelvic pain (stratum 1) or the individual change of headache (stratum 2) as determined by the change of average of the 3 highest VAS values during cycle days 22 to 28 from baseline to cycle 6. | — |
Countries
Finland, France, Germany, Spain, United Kingdom
Outcome results
None listed