Official Title: “A Phase II, Prospective, Randomized, Double-Blind, Multicenter, Dose Finding, Comparative Study for the Evaluation of the Aromatase Inhibitor Anastrozole (Multiple-Dose) Versus Clomiphene Citrate in Stimulating Follicular Growth and Ovulation in Infertile Women With Ovulatory Dysfunction”

The purpose of this study is to investigate and compare the safety and efficacy of various doses of the aromatase inhibitor (anastrozole) versus clomiphene citrate in stimulating follicular growth and ovulation in infertile women with ovulatory dysfunction.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2007

This is a multicenter, randomized, double-blind study. Upon the provision of Informed Consent, subjects will be screened for entry during the menstrual cycle prior to the anticipated start of treatment. All screening assessments should be completed within 6 weeks of treatment, unless otherwise noted.

Subjects who meet screening requirements will be equally randomized to one of the three following treatment arms: - Anastrozole 1 mg/day for 5 days - Anastrozole 5 mg/day for 5 days - Clomiphene citrate 50 mg/day for 5 days Treatment will begin at cycle day 2 or 3 of their subsequent menses (cycle day 1 = first day of full bleed).

Subjects will return to the clinic on Stimulation Days 3 or 4 and 6 or 7 (note: Stimulation Day 1 equals the first day of study drug) for blood sampling and ultrasounds. Ultrasound and serum monitoring will be repeated every 2 days thereafter until a lead follicle reaches a mean diameter of ³ 14 mm, and then daily until an LH surge occurs. Monitoring will be discontinued if a lead follicle ³ 14 mm has not developed by Stim Day 18 of the cycle (inadequate treatment cycle) with a serum progesterone being obtained one week after discontinuing monitoring.

A subgroup of subjects will be selected for additional pharmacokinetic and pharmacodynamic analysis during Cycle 1 only. Blood samples will be collected at selected timepoints for analysis of anastrozole/clomiphene citrate, estradiol, FSH, LH, androstendione, and testosterone. This subgroup will consist of approximately 40-50 subjects and will be carried out at predetermined investigative centers.

Insemination will occur via intercourse or IUI within 24 hours following the LH surge.

Subjects will return to the center during the mid-luteal phase for a pelvic ultrasound and blood sample for local and central progesterone on day 6 or 7 after the LH surge, and will also return for a repeat blood sample for progesterone on day 8 or 9 after the LH surge.

Ovulation will be confirmed by a progesterone level ³ 10 ng/mL. If the results of the progesterone test indicate that the patient has not ovulated, the subject will be brought back one to two days later for a repeat progesterone test.

In ovulatory cycles, a pregnancy test will be performed between days 15 and 20 post-LH surge.

Subjects with a positive pregnancy test will have the test repeated within 2 to 4 days and will return to the clinic between days 35-42 post-LH surge for a confirmatory ultrasound.

Subjects may be allowed to continue for up to two additional treatment cycles if they failed to achieve clinical pregnancy in their first treatment cycle, and did not experience an SAE or other mandatory withdrawal condition. Subsequent treatments will be assigned at the same dose as the randomized dose for each subject.

Intervention(s) in this Clinical Trial

• Drug: Anastrozole 1mg
  • Anastrozole 1mg, once per day for 5 days.
• Drug: Anastrozole 5mg dose
  • Anastrozole 5mg, once per day for 5 days.
• Drug: Anastrozole 10mg dose
  • Anastrozole 10mg, once per day for 5 days.
• Drug: Clomiphene Citrate 50mg
  • Clomiphene Citrate 50mg, once per day for 5 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Experimental: 3
• Active Comparator: 4

Primary Measures

• Ovulation
  • Time Frame: Up to 1 month
    Safety Issue?: No

Secondary Measures

• Pregnancy
  • Time Frame: Up to 1 month
    Safety Issue?: No

Inclusion Criteria:

• Aged 18-40
• Ovulatory dysfunction characterized by irregular and/or extended cycles
• Non-smoker

Exclusion Criteria:

• No previous gonadotropin treatment
• No more than 6 previous clomiphene treatment cycles

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: EMD Serono

Overall Clinical Trial Officials and Contacts

Donald R Tredway, M.D., PhD Study Director EMD Serono, Inc.  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00213148

Study ID Number: 25550

ClinicalTrials.gov Identifier: NCT00213148

Health Authority: United States: Food and Drug Administration