Evaluation of Efficacy and Safety of Highly Purified Urofollitropin for Ovulation Induction in Chinese Females (Compass)

A Randomized, Assessor-blinded, Parallel Group, Multi-center, Non-inferiority Study Investigating the Efficacy and Safety of Highly Purified Urofollitropin for Injection Compared to Recombinant Human Follitropin Alfa for Injection for Ovulation Induction Using a Low-dose, Step-up Protocol in Chinese Females With WHO Group II Anovulatory Infertility Failing to Conceive on Clomiphene Citrate

Evaluate the Efficacy and Safety of Highly Purified Urofollitropin for Injection Compared to Recombinant Human Follitropin Alfa for Injection for Ovulation Induction in Chinese females

Study Overview

• Status: Completed
• Conditions: Anovulation
• Intervention / Treatment: Drug: Highly Purified Urofollitropin; Drug: Recombinant Human Follitropin Alfa

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Chinese PLA General hospital
    • Beijing, Beijing, China
      • Navy General Hospital
    • Beijing, Beijing, China
      • Peking University People's Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • The Third Affiliated Hospital of Guangzhou Medical University
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital Tongji Medical College of HUST Tongji Medical College Huazhong University of Science & Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The First Affiliated Hospital with Nanjing Medical University
  • Liaoning
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Signed informed consent form prior to screening evaluations
• Chinese females between the ages of 20-39 years
• Infertility for at least 1 year before screening
• Women WHO type II anovulatory infertility with chronic anovulation (defined as amenorrhoea (i.e., no menstrual bleeding for 6 months or more) or oligoamenorrhoea (i.e., cycles of more than 35 days) ) with progestogen induced withdrawal bleeding or spontaneous menstrual bleeding
• Failure to conceive after at least one cycle of ovulation induction with clomiphene citrate
• Bilateral tubal patency documented by a hysterosalpingography or sonohysterography or laparoscopy within 2 years prior to screening
• Normal pelvis documented by a transvaginal ultrasound with respect to uterus, Fallopian tubes and ovaries within 3 months prior to screening
• Early follicular phase serum levels of FSH within normal limits (1-12 IU/L,) (results obtained within 2 months prior to randomization)
• LH (Luteinizing hormone), prolactin , E2 (estradiol), progesteron, total testosterone, and TSH (thyrotropin) levels within normal limits for the clinical laboratory
• Male partner with a semen analysis obtained within 12 months prior to randomisation and showing acceptable values for semen according to the local laboratory, or showing more than 2.000.000 progressive motile sperm per mL after capacitation (in case of IUI (intrauterine insemination))
• BMI (Body mass index) is ≥ 18.5 and < 30 kg/m2

Exclusion Criteria:

• Any known clinically significant systemic disease
• Known past or current thrombophlebitis or thromboembolism including venous thrombosis disease and active or recent arterial thrombosis disease
• Any known endocrine or metabolic abnormalities which can compromise participation in the trial with the exception of controlled thyroid function disease
• Any known concomitant medications that would interfere with evaluation of study medications. Specifically, any non-study hormonal therapy (except for thyroid medication), anti-psychotics, anxiolytics, hypnotics and sedatives, and need for continuous use of prostaglandin inhibitors (non-steroid anti- inflammatory drugs (NSAIDs), including aspirin) at the time of study entry.
• Known history of 12 or more unsuccessful (no pregnancy achieved) ovulation induction cycles
• Any known treatment with clomiphene citrate, metformin, gonadotropins or GnRH analogues within one month prior to randomisation
• Ovarian cysts with a mean diameter ≥ 15 mm that have persisted for more than one cycle or ovarian endometrioma on ultrasound
• Known at least one previous cycle experienced luteinized unruptured follicle syndrome
• Known abnormal results of cervical examination of clinical significance obtained within 1 years prior to screening
• Abnormal vaginal bleeding of undetermined origin
• Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus
• Known malformations of the sexual organs incompatible with pregnancy
• Known current or past (last 12 months) abuse of alcohol or drugs
• Known history of chemotherapy (except for gestational conditions) or radiotherapy
• Finding of any clinically relevant abnormal laboratory value
• Use of any non registered investigational drugs during 3 months before screening or previous participation in the study
• Pregnancy, lactation or contraindication to pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group	Drug: Highly Purified Urofollitropin; for Injection; Other Names: Bravelle®
Active Comparator: Comparator Group	Drug: Recombinant Human Follitropin Alfa; for Injection; Other Names: Gonal-F®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The ovulation rate defined as the percentage of subjects who present ovulation	From 6 days up to 7 weeks post hCG (human chorionic gonadotropin) administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The positive serum progesterone rate		6~9 days post hCG administration
The positive serum β-hCG/hCG rate		18~22 days post hCG administration
The clinical pregnancy rate	Regardless of fetal heart beat	6~7 weeks post hCG administration
The clinical pregnancy rate	With fetal heart beat	6~7 weeks post hCG administration
The ongoing pregnancy rate		11~12 weeks post hCG administration
The follicular development		On the day of hCG administration
Endometrial thickness		On the day of hCG administration
Total FSH (Follicle-stimulating hormone) dose administered		On the day of hCG administration
Number of FSH treatment days		On the day of hCG administration
Frequency and severity of adverse events		Expected maximum of 6 months
Frequency and severity of injection site reactions		Day 1 up to Day 28 of the ovarian stimulation period
Serum estradiol (E2) levels		On the day of hCG administration

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: August 12, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (Estimate): August 15, 2013

Study Record Updates

• Last Update Posted (Estimate): August 21, 2015
• Last Update Submitted That Met QC Criteria: August 20, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Anovulation; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: 000055