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

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

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.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Org 36286; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Org 36286 7.5 µg; 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; Org 36286 single-dose subcutaneous injection; Other Names: Corifollitropin alpha
Experimental: Org 36286 15 µg; 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; Org 36286 single-dose subcutaneous injection; Other Names: Corifollitropin alpha
Experimental: Org 36286 30 µg; 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; Org 36286 single-dose subcutaneous injection; Other Names: Corifollitropin alpha
Experimental: Org 36286 60 µg; 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; Org 36286 single-dose subcutaneous injection; Other Names: Corifollitropin alpha
Placebo Comparator: Placebo; 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; Placebo to Org 36286 as a single-dose subcutaneous injection

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Balen AH, Mulders AG, Fauser BC, Schoot BC, Renier MA, Devroey P, Struijs MJ, Mannaerts BM. Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility. J Clin Endocrinol Metab. 2004 Dec;89(12):6297-304. doi: 10.1210/jc.2004-0668.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2001
• Primary Completion (Actual): October 15, 2002
• Study Completion (Actual): October 15, 2002

Study Registration Dates

• First Submitted: June 18, 2008
• First Submitted That Met QC Criteria: June 19, 2008
• First Posted (Estimate): June 20, 2008

Study Record Updates

• Last Update Posted (Actual): February 3, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Randomized; Multi-center; Hormones; Pharmacological effects of drugs; Hormone substitutes and Hormone Antagonists; Pharmacological Actions; Multi-national; Ovulation Induction
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: P07016; 38805

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis