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

February 23, 2006
May 18, 2011
February 2005
November 2005   (final data collection date for primary outcome measure)
Pregnancy rate [ Time Frame: Day 16 ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00296465 on ClinicalTrials.gov Archive Site
Adverse events, including ovarian hyperstimulation syndrome (OHSS) [ Time Frame: Day 1 to week 5 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Dosage Strengths of Pulsatile GnRH
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

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

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

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
InFertility
  • 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: 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
  • Drug: Placebo Clomiphene Citrate
    oral placebo clomiphene citrate for 5 days
  • 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
    Interventions:
    • Drug: Pulsatile gonadotropin-releasing hormone (GnRH)
    • Drug: Placebo Clomiphene Citrate
  • 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
    Interventions:
    • Drug: Pulsatile gonadotropin-releasing hormone (GnRH)
    • Drug: Placebo Clomiphene Citrate
  • 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
    Interventions:
    • Drug: Pulsatile gonadotropin-releasing hormone (GnRH)
    • Drug: Placebo Clomiphene Citrate
  • 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
    Interventions:
    • Drug: Placebo Pulsatile GnRH
    • Drug: Placebo Clomiphene Citrate
  • 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
    Interventions:
    • Drug: Placebo Pulsatile GnRH
    • Drug: Placebo Clomiphene Citrate
  • 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
    Interventions:
    • Drug: Clomiphene Citrate
    • Drug: Placebo Pulsatile GnRH
  • 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
    Interventions:
    • Drug: Clomiphene Citrate
    • Drug: Placebo Pulsatile GnRH
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
132
November 2005
November 2005   (final data collection date for primary outcome measure)

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
Female
18 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00296465
2004-05
Yes
Clinical Development Support, Ferring Pharmaceuticals
Ferring Pharmaceuticals
Not Provided
Study Director: Clinical Development Support Ferring Pharmaceuticals
Ferring Pharmaceuticals
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP