Anovulation in women with PCOS MedDRA version: 16.1 Level: PT Classification code 10033312 Term: Ovulation induction System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 16.1 Level: LLT Classification code 10065161 Term: Polycystic ovarian syndrome System Organ Class: 100000004872
Conditions
Interventions
Trade Name: GONAL-f
Product Name: GONAL-f
Pharmaceutical Form: Injection
Concentration unit: IU/ml international unit(s)/millilitre
Conc
Sponsors
Merck Serono
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1Inclusion criteria: To be eligible for inclusion into this trial, the subjects must fulfill all the following criteria: 1. Subjects eligible for ovulation induction treatment, where monofollicular development is the desired treatment outcome and the dose schedule outlined in the protocol is deemed appropriate. 2. Premenopausal female subjects, aged between 18 and 37 years inclusive. 3. Subjects desirous of pregnancy / willing to conceive. 4. Subjects who are infertile due to chronic anovulation demonstrated by a cycle duration of >35 days. 5. Subjects who have been treated with clomifene citrate therapy, according to standard site practice, and have failed to ovulate and/or conceive. Patients who did not conceive after clomifene therapy, even if the therapy resulted in follicular development, are eligible for inclusion in the study. Those patients who did conceive after clomifene treatment and then had a subsequent miscarriage are not eligible for the study. Any miscarriages that occurred separately to their treatment with clomifene do not make the patient ineligible as long as they have had less than 3 miscarriages and have also failed treatment with clomifene (as described above). 6. Subjects with FSH serum values within the normal range in the early follicular phase. 7. Subjects with an overall total antral follicle count (AFC) >10 (of follicle size =2 mm and 20 and =32 kg/m2 11. Subjects with negative cervical Papanicolaou (PAP) test conducted according to national guidelines and/or standard site practice. 12. Male partners of female subjects with sperm compatible with non-assisted fertilisation or availablility of donor sperm, as confirmed by the Investigator. 13. Subjects who are willing and able to comply with protocol requirements and have provided written, informed consent. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 116 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Exclusion criteria To be eligible for inclusion in this trial the subjects must not meet any of the following criteria: 1. Subjects with history of hypersensitivity to the investigational medicinal product (IMP; active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f) or any other drug used in the trial (i.e. Ovitrelle). 2. Subjects with ovarian enlargement or ovarian cyst unrelated to polycystic ovary syndrome (PCOS), and of unknown origin on ultrasound. 3. Subjects with evidence of diminished ovarian reserve (cycle length <26 days; FSH above the upper limit of local serum FSH values, total AFC in both ovaries <10). 4. Subjects with uterine pathology/abnormalities, which in the opinion of the investigator could impair pregnancy evolution. 5. Subjects who have undergone three or more previous miscarriages. 6. Subjects with any previous extrauterine pregnancy. 7. Pregnant or lactating female subjects. 8. Subjects with abnormal gynaecological bleeding of unknown aetiology. 9. Subjects with previous history of severe ovarian hyperstimulation syndrome (OHSS; after clomifene treatment). 10. Subjects who have evidence of current or previous pelvic inflammatory disease before treatment assignment. 11. Subjects with tumours of the hypothalamus and pituitary gland. 12. Subjects with ovarian, uterine or mammary carcinoma. 13. Subjects treated with clomifene citrate or gonadotropins within 1 month of the screening evaluation. 14. Subjects with any medical condition which, in the opinion of the investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy. 15. Subjects with any medical condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug. 16. Subjects with clinically significant abnormal prolactin (PRL) serum values in the early follicular phase. 17. Subjects with any clinically significant systemic disease (e.g. insulin-dependent diabetes) or any contraindication to being pregnant and/or carrying a pregnancy to term. 18. An active substance abuser. 19. Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner. 20. Subjects who are currently participating in another clinical trial. 21. Subjects who are unable to give written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary research question in this study is whether a low dose FSH treatment method, with smaller dose increase increments, can be considered ‘non-inferior’ to (i.e. not worse than) an established low-dose FSH treatment when trying to achieve adequate growth of just one follicle (containing an egg) in anovulatory women. ; Secondary Objective: To investigate the number of treatment cycles that result in the growth of two follicles. To investigate the number of treatment cycles that result in the growth of more than two follicles To investigate the number of treatment cycles that result in ovulation (after hCG). To report the number of cycles where hCG was not given -due to inadequate follicle growth after 5 weeks of rFSH stimulation. -due to excessive follicle growth. To report the number of cycles resulting in a pregnancy - positive pregnancy test - clinical pregnancy confirmed by ultrasound scan To report the number of multiple pregnancies To report the number miscarriages after confirmation of clinical pregnancy (by ultrasound scan) To report the number of cycles with an adverse event - Ovarian Hyper Stimulation Syndrome. - local tolerability (injection site reactions). - other. To report the average duration of Gonal-f treatment in each cycle. To report the average total dose of Gonal-f ;Primary end point(s): The proportion of cycles with monofollicular development (defined as only one follicle >17mm and no other follicles > 14mm following up to 4 weeks Gonal-f treatment).;Timepoint(s) of evaluation of this end point: Following completion of treatment with Gonal-f (up to 4 weeks). Ultrasound scan at final adhoc clinic visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Follicular development will be assessed following a maximum of 4 weeks treatment with Gonal-f. All other endpoints will be assessed following confirmation of clinical pregnancy. ; Secondary end point(s): • Proportion of cycles with bifollicular development (defined as only two follicle >17mm following up to 4 weeks Gonal-f treatment). • Proportion of cycles with multifollicular development (defined as three or more follicles >14mm following up to 4 weeks Gonal-f treatment). • Proportion of ovulatory cycles (after hCG). • Proportion of cycles where hCG was not given o due to inadequate follicle development after 4 weeks of rFSH. o due to excessive response. • Proportion of cycles resulting in a pregnancy o positive pregnancy test. o clinical pregnancy (at least one foetal sac on ultrasound 35 to 42 days after hCG). • Number and incidence of multiple pregnancy (and number of foetuses). • Number and incidence of miscarriages after confirmation of clinical pregnancy • Number and proportion of cycles with an adverse event o OHSS (and grade). o local tolerability. o other. • Duration of rFSH stimulation (days) prior to hCG. • Total dose (IU) of rFSH administered per cycle. • AMH level reported at Baseline and last visit pre-hCG, and difference in AMH levels between these visits. • Testosterone levels at baseline reported with outcome of OI cycle. • SHBG levels at baseline reported with outcome of OI cycle. | — |
Countries
Ireland, United Kingdom
Contacts
Public ContactSusan O'Connor
Quanticate
Outcome results
None listed