E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Polycystic ovary syndrome (PCOS) is a disorder characterized by polycystic ovaries, oligo-amenorrhea and hyperandrogenism. It is the most common endocrine disorder in women of fertile age. PCOS women are an-or oligoovulatory and often suffer from infertility or subfertility. Prevalence estimates vary between three and twenty persent depending on the diagnostic criteria used and the population studied. A prevalence of five to seven percent has been reported in Caucasian women. | |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | Does metformin treatment before IVF/ICSI in women with polycystic ovary syndrome and normal weight (BMI below 28 kg/m2) increase clinical pregnancy rate in IVF/ICSI? Clinical pregnancy is defined as a viable intrauterine pregnancy at 7 weeks. | |
E.2.2 | Secondary objectives of the trial | •Number of oocytes collected •Embryo quality •Number of days with gonadotrophin treatment •Dose of Gonadotrophin , total pr. cycle and daily. •Serum estradiol on day of hCG administration •Occurrence of Ovarian Hyperstimulation Syndrome (OHSS) •Spontaneous pregnancy rates during the pre-treatment period. •Spontaneous abortion rates •Live Birth Rates | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria | •Infertile (> 1 year) PCOS-women planned for treatment with IVF/ICSI •First or second cycle of IVF/ICSI - treatment •Age < 38 years at inclusion •BMI < 28 kg/m² at inclusion •Patient willing to be randomised to 4 months treatment with metformin or placebo •Patient has given written informed consent •If previously on metformin, a one-month washout period is required before inclusion. •PCOS –diagnosis based on the Rotterdam revised criteria 2003 / ESHRE-ASRM criteria – fulfilling at least two out of the following three criteria: 1.Oligo-amenorrea. 2.Hyperandrogenism 3.Polycystic ovaries by ultrasound | |
E.4 | Principal exclusion criteria | More than one previous IVF cycle Patients not suitable for starting dose 112,5 IE Gonal-F Basal s-FSH more than 10 IU/L Known liver disease, or s-ALAT > 80 IU/l Known renal disease, or s-kreatinin > 130 mmol/l Known alcoholism or drug abuse Known diabetes mellitus or fasting plasma glucose ≥6.7 mmol/L Per oral steroid hormone treatment Treatment with cimetidin, anticoagulantia, erythromycin, or other macrolides. Hyperprolactinemia (s-Prolactin > 700 mIE/L) Abnormal thyroid function tests Congenital adrenal hyperplasia Androgen secreting tumors Cushing’s syndrome Unfit to participate of any other reason | |
E.5 End points |
E.5.1 | Primary end point(s) | Clinical pregnancy rate following IVF/ICSI treatment in normal weight PCOS-women. Clinical pregnancy is defined as a viable intrauterine pregnancy at 7 weeks. | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 | The trial involves single site in the Member State concerned | No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | End of trailis when the last baby following the treatment is born. | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |