Comparison of Anastrozole Verses Clomiphene Citrate in Stimulating Follicular Growth and Ovulation in Infertile Women With Ovulatory Dysfunction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00213148
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : August 6, 2014
Information provided by (Responsible Party):
EMD Serono

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Anovulation Drug: Anastrozole 1mg Drug: Anastrozole 5mg dose Drug: Anastrozole 10mg dose Drug: Clomiphene Citrate 50mg Phase 2

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 271 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : March 2005
Actual Primary Completion Date : December 2007
Actual Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility

Arm Intervention/treatment
Experimental: 1 Drug: Anastrozole 1mg
Anastrozole 1mg, once per day for 5 days.

Experimental: 2 Drug: Anastrozole 5mg dose
Anastrozole 5mg, once per day for 5 days.

Experimental: 3 Drug: Anastrozole 10mg dose
Anastrozole 10mg, once per day for 5 days.

Active Comparator: 4 Drug: Clomiphene Citrate 50mg
Clomiphene Citrate 50mg, once per day for 5 days.

Primary Outcome Measures :
  1. Ovulation [ Time Frame: Up to 1 month ]

Secondary Outcome Measures :
  1. Pregnancy [ Time Frame: Up to 1 month ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00213148

United States, Massachusetts
Local US Medical Information
Rockland, Massachusetts, United States, 02370
Sponsors and Collaborators
EMD Serono
Study Director: Donald R Tredway, M.D., PhD EMD Serono

Responsible Party: EMD Serono Identifier: NCT00213148     History of Changes
Other Study ID Numbers: 25550
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: August 6, 2014
Last Verified: August 2014

Additional relevant MeSH terms:
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Citric Acid
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators