Study to Assess the Efficacy and Safety of Three Dosage Strengths of Pulsatile GnRH Delivered From a Iontophoretic Patch Compared to Oral Treatment With Clomiphene or Placebo in Infertile Females

A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Dosage Strengths of Pulsatile GnRH Delivered From a Iontophoretic Patch (Lutrepatch) Compared to Oral Treatment With Clomiphene Citrate or Placebo in Anovulatory or Oligoovulatory Infertile Females

The primary objective of this study is to determine the safety and efficacy of pulsatile GnRH delivered from a iontophoretic patch (Lutrepatch) for induction of ovulation in women with anovulatory/ oligoovulatory infertility, compared to placebo and to a reference treatment with clomiphene citrate.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: GnRH iontophoretic transdermal Lutrepatch; Drug: GnRH iontophoretic transdermal Lutrepatch; Drug: GnRH iontophoretic transdermal Lutrepatch; Drug: placebo clomiphene citrate; Drug: clomiphene citrate; Drug: placebo GnRH patch

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Watching Over Mothers and Babies Foundation
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Women's Clinic
  • California
    • San Diego, California, United States, 92130
      • San Diego Fertility Center
    • San Ramon, California, United States, 94583
      • Compass Clinical Research
    • Vista, California, United States, 92083
      • North Coast Women's Care Medical Group
    • Westlake Village, California, United States, 91361
      • Huntington Reproductive Center
  • Florida
    • Clearwater, Florida, United States, 33759
      • Florida Fertility Institute
    • Plantation, Florida, United States, 33324
      • All Women's Healthcare of Wesy Broward, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Georgia Reproductive Specialists
    • Atlanta, Georgia, United States, 30328
      • Atlanta Center for Reproductive Medicine
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Women's Health Practice
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • University of Kentucky
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70815
      • A Woman's Center for Reproductive Medicine
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Shady Grove Fertility Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Hutzel Women's Health Specialists
    • Hamtramck, Michigan, United States, 48212
      • CAREM Canadian American Reproductive Medicine
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Women's Clinic of Lincoln, P.C.
  • Nevada
    • Las Vegas, Nevada, United States, 89117
      • Fertility center of Las Vegas
    • Reno, Nevada, United States, 89502
      • The Medical Group of Northern Nevada
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Women's Health Research Center LLC
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Gynecologic Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45209
      • Institute for Reproductive Health
    • Cincinnati, Ohio, United States, 45267-0457
      • Greater Cincinnati OB/GYN, Inc./Reproductive Medicine Research
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Clinical Trials of America Inc
    • Portland, Oregon, United States, 97239
      • Center for Health and Healing
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Memphis Associates, LLC
  • Texas
    • Bedford, Texas, United States, 76022
      • Center for Assisted Reproduction
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
    • Webster, Texas, United States, 77598
      • Center of Reproductive Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Females between the ages of 18 and 38 years
2. Desire to become pregnant

3. Infertile due to ovulatory dysfunction as described below:

   • Unable to conceive for at least 1 year and
   • Anovulatory (defined as 4 or fewer menstrual cycles per year) or Oligo-ovulatory (defined as menstrual cycle frequency > 45 days)

Exclusion Criteria:

1. Requires donor oocytes or sperm
2. Two or more failed (defined as no biochemical pregnancy achieved) gonadotropin fertility treatment cycles - if previous gonadotropin success, no more than two failed subsequent cycles
3. Use of insulin-sensitizing drugs (e.g., Metformin) within 1 month prior to progesterone challenge

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GnRH High Target Delivery; 10 mg GnRH iontophoretic transdermal Lutrepatch with a high target delivery of pulsatile GnRH (every 90 minutes) for 21 days and oral placebo clomiphene citrate for 5 days	Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day (every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'high target' study dose, which is estimated to be 800 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day(every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'medium target' study dose, which is estimated to be 400-600 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day (every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'low target' study dose, which is estimated to be 200 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: placebo clomiphene citrate; oral, taken for 5 days
Experimental: GnRH Medium Target Delivery; 10 mg GnRH iontophoretic transdermal Lutrepatch with a medium target delivery of pulsatile GnRH (every 90 minutes) for 21 days and oral placebo clomiphene citrate for 5 days	Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day (every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'high target' study dose, which is estimated to be 800 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day(every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'medium target' study dose, which is estimated to be 400-600 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day (every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'low target' study dose, which is estimated to be 200 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: placebo clomiphene citrate; oral, taken for 5 days
Experimental: GnRH Low Target Delivery; 10 mg GnRH iontophoretic transdermal Lutrepatch with a low target delivery of pulsatile GnRH (every 90 minutes) for 21 days and oral placebo clomiphene citrate for 5 days	Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day (every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'high target' study dose, which is estimated to be 800 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day(every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'medium target' study dose, which is estimated to be 400-600 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: GnRH iontophoretic transdermal Lutrepatch; 10 mg GnRH iontopheretic transdermal patch. A new patch is applied two times each day (every 12 hours). Delivery current and membrane thickness adjusted to deliver the 'low target' study dose, which is estimated to be 200 picograms/ml; Other Names: Lutrepatch; Gonadotropin-releasing hormone (GnRH); Drug: placebo clomiphene citrate; oral, taken for 5 days
Active Comparator: Clomiphene Citrate; Placebo GnRH iontophoretic transdermal Lutrepatch with a high target delivery of pulsatile current (every 90 minutes) for 21 days and oral 50 mg clomiphene citrate for 5 days	Drug: clomiphene citrate; Oral, 50 mg daily for 5 days; Other Names: various tradenames; Drug: placebo GnRH patch; Placebo transdermal patch with a high target delivery of placebo(every 90 minutes). New patch to be applied every 12 hours.
Placebo Comparator: Placebo; Placebo GnRH iontophoretic transdermal Lutrepatch with a high target delivery of pulsatile current (every 90 minutes) for 21 days and oral placebo clomiphene citrate for 5 days	Drug: placebo clomiphene citrate; oral, taken for 5 days; Drug: placebo GnRH patch; Placebo transdermal patch with a high target delivery of placebo(every 90 minutes). New patch to be applied every 12 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ovulation rate	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pregnancy rate	30 days
Incidence of Ovarian Hyperstimulation Syndrome (OHSS)	30 days
Incidence of skin irritation	30 days

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: November 20, 2008
• First Submitted That Met QC Criteria: November 21, 2008
• First Posted (Estimate): November 24, 2008

Study Record Updates

• Last Update Posted (Estimate): September 9, 2015
• Last Update Submitted That Met QC Criteria: August 26, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: anovulatory/oligoovulatory infertility
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Anticoagulants; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Chelating Agents; Sequestering Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Calcium Chelating Agents; Hormones; Citric Acid; Sodium Citrate; Clomiphene; Enclomiphene; Zuclomiphene; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 2008-03