Partial Double-Blind, Placebo-Controlled Study to Assess the Effect of Anastrozole on the Endometrium in Healthy Volunteers

A Partial Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Anastrozole, an Aromatase Inhibitor, on Endometrial Thickness in Healthy Premenopausal Women When Dosed at Various Times During the Menstrual Cycle (Protocol M-001)

Aromatase inhibitors have been approved for use in postmenopausal women to treat and prevent breast cancer. They act by blocking the action of the enzyme, aromatase, that is necessary for the production of estradiol. This class of drugs, aromatase inhibitors, are very effective in reducing estradiol levels in postmenopausal women and in treating estrogen receptor positive breast cancers. This study is examining the effect of a specific inhibitor, anastrozole, on endometrial thickness in premenopausal women. The endometrium is sensitive to estradiol and also has local aromatase which, if inhibited, may result in reduced endometrial thickness. The main hypothesis is that anastrozole can be administered at any time during the menstrual cycle and reduce endometrial thickness compared to placebo.

Study Overview

• Status: Completed
• Conditions: Menstruation Disorders
• Intervention / Treatment: Drug: Anastrozole

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Jasper Research Clinic
    • Southfield, Michigan, United States, 48034
      • University Women's Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Between the ages of 25 and 45 and pre-menopausal;
• Non-lactating and not pregnant
• able to follow the schedule of procedures
• able to freely provide informed consent
• have clinically acceptable physical examination and safety laboratory studies

Exclusion Criteria:

• current use of any form of systemic contraceptive
• have self-reported irregular menstrual cycles
• intercurrent illness(es) detected on the screening physical
• unwilling or unable to use barrier methods of contraception
• have evidence of endometrial polyps or myomata on TVU/SIS that would interfere with endometrial thickness measurement
• detection of ovarian cyst(s) during adnexal examination on screening TVU/SIS measuring greater than 5 cm
• have history of, or current cancer, on any form exclusive of basal cell carcinoma
• BMI >= 35
• history of alcohol or drug abuse in the past 5 years
• unwilling or unable to undergo study procedures within the necessary time frames
• history or current liver abnormalities as defined by ALT or AST > 2X ULN
• treated or untreated diabetes defined as fasting blood sugar >= 126 mg/dL
• untreated hypertension
• impaired renal function by estimated creatinine clearance < 80mL/min
• have estradiol levels < 20 pg/ml and FSH levels > 40 mIU/mL or
• have a history of adverse reaction any aromatase inhibitor

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anastrozole - A; Treatment for 26 consecutive days	Drug: Anastrozole
Experimental: Anastrozole -B; Treatment for 7 consecutive days early in menstrual cycle	Drug: Anastrozole
Experimental: Anastrozoe - C; Treatment for 7 consecutive days mid follicular phase	Drug: Anastrozole
Experimental: Anastrozole - D; Treatment for 7 consecutive days - mid cycle	Drug: Anastrozole
Experimental: Anastrozole - E; Treatment for 7 consecutive days - luteal	Drug: Anastrozole
Placebo Comparator: Anastrozole - F; Treatment with placebo for 26 consecutive days	Drug: Anastrozole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Endometrial thickness as measured by transvaginal ultrasound, safety	Over one menstrual cycle

Collaborators and Investigators

• Sponsor: Meditrina Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: April 27, 2007
• First Submitted That Met QC Criteria: April 27, 2007
• First Posted (Estimate): April 30, 2007

Study Record Updates

• Last Update Posted (Estimate): June 3, 2009
• Last Update Submitted That Met QC Criteria: June 2, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Menstruation Disturbances; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: M-001