Study to Investigate the Optimal Dose of Org 36286 to Induce Monofollicular Ovulation in Women With WHO Group II Anovulatory Infertility (P07016)

Study Overview
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Brief Summary
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The objectives of this trial were to investigate the feasibility and the optimal dose of a single administration of Org 36286 to induce monofollicular ovulation in women with WHO Group II anovulatory infertility and to assess the safety (including the absence of antibody formation) of Org 36286.

Detailed Description
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This was a phase II, randomized, double-blind, placebo controlled, comparative trial to investigate the optimal dose of a single administration of Org 36286 to induce monofollicular ovulation in women with WHO Group II anovulatory infertility. Treatment injection was given on Day 1-3 after the onset of a spontaneous or progestagen induced withdrawal bleeding. After injection, ultrasound monitoring and sampling for serum hormones were done on treatment Days 3, 5, and daily from Day 7 to 21 or until a urinary luteinizing hormone (LH) peak was detected. From treatment Day 7 the urinary LH response was assessed to detect the preovulatory LH peak. In case of hyperstimulation, production of endogenous gonadotropins could be suppressed by giving daily injections of GnRH antagonist. Post-treatment assessments were done in the third week after the urinary LH peak. If no LH peak was detected, posttreatment assessments were performed four to five weeks after Org 36286 or placebo injection.

Official Title
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A Phase II, Randomized, Double-blind, Placebo-controlled, Comparative Trial to Investigate the Optimal Dose of a Single Administration of Org 36286 (Corifollitropin Alfa) to Induce Monofollicular Ovulation in Women With WHO Group II Anovulatory Infertility

Conditions
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Infertility

Intervention / Treatment
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* Drug: Org 36286
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Wish to conceive; Oligomenorrhea (cycle length >=41 days) or amenorrhea (no menstrual cycle for >6 months); Body Mass Index (BMI) >=18 and <=32 kg/m^2; Serum FSH levels within normal limits (1-10 IU/L); Normal serum prolactin and thyroid stimulating hormone (TSH) levels; Progestagen induced withdrawal bleeding or spontaneous menstrual bleeding; Exclusion Criteria: Tumours of the ovary, breast, uterus, pituitary or hypothalamus; Pregnancy or lactation; Undiagnosed vaginal bleeding; Ovarian cysts or enlarged ovaries not related to polycystic ovarian disease (PCOD); Any ovarian and/or abdominal abnormality interfering with ultrasound examination; Malformations of the sexual organs incompatible with pregnancy; Clomiphene resistance with documented anovulation (treated with 150 mg clomiphene for five days and no ovulation); Treatment with metformin, gonadotropins, or GnRH analogs within 90 days prior to the start of Org 36286 treatment; Treatment with clomiphene citrate within 42 days prior to the start of Org 36286 treatment; Alcohol or drug abuse within the 12 months preceding signing of informed consent; Any clinically relevant abnormal laboratory value; Hypersensitivity to any of the substances in Org 36286; Hypersensitivity to Orgalutran® or any of its components; Use of any investigational drugs during 90 days before screening or previous participation in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Org 36286 7.5 µg<br>Org 36286 7.5 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. | Drug: Org 36286<br>* Org 36286 single-dose subcutaneous injection<br>* Other names: Corifollitropin alpha;|
| Experimental: Org 36286 15 µg<br>Org 36286 15 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. | Drug: Org 36286<br>* Org 36286 single-dose subcutaneous injection<br>* Other names: Corifollitropin alpha;|
| Experimental: Org 36286 30 µg<br>Org 36286 30 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. | Drug: Org 36286<br>* Org 36286 single-dose subcutaneous injection<br>* Other names: Corifollitropin alpha;|
| Experimental: Org 36286 60 µg<br>Org 36286 60 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. | Drug: Org 36286<br>* Org 36286 single-dose subcutaneous injection<br>* Other names: Corifollitropin alpha;|
| Placebo Comparator: Placebo<br>Placebo to Org 36286 administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. | Drug: Placebo<br>* Placebo to Org 36286 as a single-dose subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Ovulation Rate in Monofollicular Cycles |  | Up to 2 Weeks Following LH Peak | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Overall Ovulation Rate |  | Up to 2 Weeks Following LH Pek | 
| Number of Participants With Cancellation of Menstrual Cycle |  | Up to Day 21 | 
| Participant Follicle Size |  | Up to Day 21 | 
| Number of Participants With Miscarriages, Biochemical, Ectopic, Clinical, Vital, Single, or Multiple Ongoing Pregnancies |  | Up to 10 Weeks Following Ovulation | 
| Number of Participants Experiencing Serious Adverse Events (SAEs) |  | Up to 10 Weeks Following Ovulation | 
| Number of Participants With Clinically Significant Laboratory Abnormalities |  | Up to 3 Weeks Following Ovulation | 
| Number of Participants With Clinically Significant Changes in Vital Signs |  | Up to 3 Weeks Followiing Ovulation | 
| Number of Participants With Antibodies to Org 36286 |  | Up to 3 Weeks Following Ovulation | 
| Participant Serum Follicle Stimulating Hormone (FSH) Level |  | Up to Day 21 | 
| Participant Serum LH Level |  | Up to Day 21 | 
| Participant Inhibin-B, E2, and P Serum Concentration |  | Up to Day 21 | 
| Number of Participants with Ovarian Hyperstimulation Syndrome (OHSS) |  | Up to 2 Weeks Following LH Peak | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovulation Induction, Pharmacological effects of drugs, Hormones, Hormone substitutes and Hormone Antagonists, Pharmacological Actions, Randomized, Multi-center, Multi-national