A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Dosage Strengths of Pulsatile GnRH

This study has been completed.
Sponsor:
Information provided by:
Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00296465
First received: February 23, 2006
Last updated: May 18, 2011
Last verified: May 2011
  Purpose

This study will be performed in approximately 132 women with anovulatory/oligoovulatory infertility.


Condition Intervention Phase
InFertility
Drug: Pulsatile gonadotropin-releasing hormone (GnRH)
Drug: Clomiphene Citrate
Drug: Placebo Pulsatile GnRH
Drug: Placebo Clomiphene Citrate
Phase 2
Phase 3

Ferring Pharmaceuticals has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Dosage Strengths of Pulsatile GnRH Administered Intravenously or Subcutaneously (Via Portable Infusion Pump) Compared to Oral Treatment With Clomiphene Citrate in Anovulatory or Oligoovulatory Infertile Females

Resource links provided by NLM:


Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:
  • Pregnancy rate [ Time Frame: Day 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events, including ovarian hyperstimulation syndrome (OHSS) [ Time Frame: Day 1 to week 5 ] [ Designated as safety issue: Yes ]

Enrollment: 132
Study Start Date: February 2005
Study Completion Date: November 2005
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lutrepulse® 5mcg IV
5.0 mcg Pulsatile GnRH (Lutrepulse®) administered intravenously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks and oral placebo clomiphene citrate for 5 days
Drug: Pulsatile gonadotropin-releasing hormone (GnRH)
Dosages as specified, administered either subcutaneously (SC) or intraveneously (IV) as specified, via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Other Name: Lutrepulse®
Drug: Placebo Clomiphene Citrate
oral placebo clomiphene citrate for 5 days
Experimental: Lutrepulse® 10 mcg IV
10.0 mcg Pulsatile GnRH (Lutrepulse®) administered intravenously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks and oral placebo clomiphene citrate for 5 days
Drug: Pulsatile gonadotropin-releasing hormone (GnRH)
Dosages as specified, administered either subcutaneously (SC) or intraveneously (IV) as specified, via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Other Name: Lutrepulse®
Drug: Placebo Clomiphene Citrate
oral placebo clomiphene citrate for 5 days
Experimental: Lutrepulse® 20 mcg SC
20.0 mcg Pulsatile GnRH (Lutrepulse®) administered subcutaneously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks and oral placebo clomiphene citrate for 5 days
Drug: Pulsatile gonadotropin-releasing hormone (GnRH)
Dosages as specified, administered either subcutaneously (SC) or intraveneously (IV) as specified, via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Other Name: Lutrepulse®
Drug: Placebo Clomiphene Citrate
oral placebo clomiphene citrate for 5 days
Placebo Comparator: Placebo IV
Placebo Pulsatile GnRH (Lutrepulse®) administered intravenously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks and oral placebo clomiphene citrate for 5 days
Drug: Placebo Pulsatile GnRH
Administered either intravenously or subcutaneously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Drug: Placebo Clomiphene Citrate
oral placebo clomiphene citrate for 5 days
Placebo Comparator: Placebo SC
Placebo Pulsatile GnRH (Lutrepulse®) administered subcutaneously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks and oral placebo clomiphene citrate for 5 days
Drug: Placebo Pulsatile GnRH
Administered either intravenously or subcutaneously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Drug: Placebo Clomiphene Citrate
oral placebo clomiphene citrate for 5 days
Active Comparator: Clomiphene Citrate/Placebo IV
Oral clomiphene citrate (over encapsulated) for 5 days and Placebo Pulsatile GnRH (Lutrepulse®) administered intravenously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Drug: Clomiphene Citrate
Oral clomiphene citrate (over encapsulated) for 5 days
Other Name: Clomid
Drug: Placebo Pulsatile GnRH
Administered either intravenously or subcutaneously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Active Comparator: Clomiphene Citrate / Placebo SC
Oral clomiphene citrate (over encapsulated) for 5 days and Placebo Pulsatile GnRH (Lutrepulse®) administered subcutaneously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks
Drug: Clomiphene Citrate
Oral clomiphene citrate (over encapsulated) for 5 days
Other Name: Clomid
Drug: Placebo Pulsatile GnRH
Administered either intravenously or subcutaneously via portable infusion pump in a pulsatile fashion (every 90 minutes) for 4 weeks

Detailed Description:

This multicenter, randomized, double-blind, placebo-controlled study will be performed in approximately 132 women with anovulatory/oligoovulatory infertility. The treatment duration will be approximately 4 weeks with pulsatile GnRH or placebo and 5 days with Clomiphene Citrate or placebo. All subjects will be screened based on inclusion/exclusion criteria, medical/infertility history and general safety assessments. Subjects that complete screening will be dispensed 100 mg of oral progesterone twice a day for 10 days to induce uterine bleeding. On Cycle Day 5 from the start of bleeding the subject will be randomly assigned to 1 of 7 treatment groups. All subjects will be monitored weekly throughout the 4 week treatment period for ovulation and intercourse will be timed. All subjects will be required to return to the study center for a total of 8 visits. In addition, all subjects with a confirmed clinical pregnancy will be monitored until fetal heartbeat is confirmed at approximately 5-6 weeks gestation

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  1. Females between the ages of 18 (or 19 in the State of Alabama) and 40 years.
  2. Infertile due to ovulatory dysfunction as described below:
  3. Positive progesterone withdrawal test following the screening visit.
  4. TSH (thyroid-stimulating hormone) levels within normal limits for the clinical laboratory or considered not clinically significant (eg, secondary to exogenous thyroid medication) by the investigator
  5. Normal insulin sensitivity assessed as ratio of fasting blood glucose to fasting insulin > 4.5 at Screening
  6. Male partner with recent (within 6 months prior to screening) semen analysis showing normalcy according to the local laboratory normal criteria. If screening semen analysis is borderline, the couple will be accepted into the study only if a second sample obtained prior to screening is adequate.
  7. Presence of both ovaries, without evidence of clinically significant abnormality, as detected by transvaginal ultrasound
  8. Normal transvaginal ultrasound with respect to uterus and adnexa (eg, no hydrosalpinx)
  9. Hysterosalpingography or hysteroscopy or sonohysterogram documenting a uterine cavity consistent with expected normal function and patency of the fallopian tubes within the previous 3 years prior to screening (within 1 year prior to screening there should be no pelvic infection, endometriosis or pelvic surgery).
  10. Negative serum pregnancy test (qualitative) prior to the progesterone test
  11. Desire to become pregnant

Exclusion Criteria

  1. Requires donor oocytes or sperm
  2. Previous and current use of infertility modifiers, including insulin-sensitizing drugs
  3. Primary amenorrhea/hypogonadotropic hypogonadism (eg, isolated gonadotropin deficiency or evidence of primary/premature ovarian failure)
  4. Presence of any clinically relevant systemic disease (eg, diabetes mellitus, pituitary tumor, anorexia nervosa).
  5. Surgical or medical condition which in the judgment of the Investigator or Sponsor may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used.
  6. Any pregnancy within last 3 months prior to Screening.
  7. Patients with a body mass index (BMI) >30 at time of Screening
  8. Total testosterone and DHEA-S >1.5 times the upper limits of normal laboratory range and prolactin > 20 ng/mL
  9. Presence of abnormal uterine bleeding of undetermined origin.
  10. Active or prior history of substance abuse
  11. History of chemotherapy (except for gestational conditions) or radiotherapy
  12. Currently breast feeding, pregnant or contraindication to pregnancy
  13. Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled clinic visits and laboratory tests.
  14. Documented intolerance or allergy to any of the medications used including the study medication
  15. Participation in any experimental drug study within 60 days prior to Screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00296465

Locations
United States, Louisiana
Southern Fertility Center and Clinical Research
Metairie, Louisiana, United States, 70002
Sponsors and Collaborators
Ferring Pharmaceuticals
Investigators
Study Director: Clinical Development Support Ferring Pharmaceuticals
  More Information

No publications provided

Responsible Party: Clinical Development Support, Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00296465     History of Changes
Other Study ID Numbers: 2004-05
Study First Received: February 23, 2006
Last Updated: May 18, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Citric Acid
Clomiphene
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on July 24, 2014