Fasting Study of Letrozole Tablets 2.5 mg and Femara® Tablets 2.5 mg

Single-Dose Fasting Bioequivalence Study of Letrozole Tablets (2.5 mg; Mylan) and Femara® Tablets (2.5 mg; Novartis) in Healthy Postmenopausal Female Volunteers

The objective of this study was to investigate the bioequivalence of Mylan's letrozole 2.5 mg tablets to Novartis' Femara® 2.5 mg tablets following a single, oral 2.5 mg (1 x 2.5 mg) dose administered under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Letrozole Tablets 2.5 mg; Drug: Femara® Tablets 2.5 mg

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33181
      • SFBC International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age: 40 years or older.
2. Sex: Females only.
3. Weight: At least 52 kg (115 lbs) and within 30% of Ideal Body Weight (IBW), as referenced by the Table of ""Desirable Weights of Adults"" from Metropolitan Life Insurance Company, 1999 (See Part II: ADMINISTRATIVE ASPECTS OF HUMAN BIOAVAILABILITY PROTOCOLS).
4. Absence of menses for one year for postmenopausal subjects, or at least 6 weeks for oophorectomized subjects. (For oophorectomized subjects, an operative report documenting bilateral oophorectomy and surgical pathology report documenting the absence of malignant disease.)
5. Baseline FSH and 17β-estradiol serum levels consistent with postmenopausal status confirmed within 72 hours of initiation of study medication (FSH greater than or equal to 40 mIU/mL; 17β-estradiol less than or equal to 31 pg/mL).
6. All subjects should be judged normal and healthy during a pre-study medical evaluation (physical examination, laboratory evaluation, 12-lead ECG, Hepatitis B, Hepatitis C and HIV tests, and urine drug screen including amphetamine, barbiturates, benzodiazepines, cannabinoid, cocaine, opiates, phencyclidine, and methadone) performed within 21 days of the initial dose of study medication.

7. The physical examination shall include pelvic and breast exams.

   1. Pelvic findings should be consistent with hypoestrogenemia.
   2. A mammogram will be required if not performed within the last 12 months.
   3. A Papanicolaou ("Pap") smear will be required on subjects with an intact uterus and cervix if not performed within the last 6 months.

Exclusion Criteria:

1. Institutionalized subjects will not be used.

2. Social Habits:

   1. Use of any tobacco-containing products within 1 year of start of study.
   2. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.
   3. Ingestion of any vitamins or herbal products within 7 days prior to the initial dose of the study medication.
   4. Any recent, significant change in dietary or exercise habits.
   5. A positive test for any drug included in the urine drug screen.
   6. History of drug and/or alcohol abuse.

3. Medications:

   1. Use of any prescription or over-the-counter (OTC) medications within the 14 days prior to the initial dose of study medication.
   2. Use of any medication known to alter hepatic enzyme activity within 28 days prior to the initial dose of study medication.
   3. Use hormonal replacement therapy within 3 months prior to the initial dose of study medication.

4. Diseases:

   1. History of any significant chronic disease such as (but not limited to): 1. Thrombotic disorders. 2. Coronary artery or cerebrovascular disease. 3. Liver, kidney or gallbladder dysfunction/disorder(s). 4. Diabetes or any other endocrinological disease. 5. Estrogen-dependent neoplasia. 6. Postmenopausal uterine bleeding. 7. Endometrial hyperplasia.
   2. Acute illness at the time of either the pre-study medical evaluation or dosing.
   3. A positive HIV, Hepatitis B, or Hepatitis C test.

5. Abnormal and clinically significant laboratory test results:

   1. Clinically significant deviation from the Guide to Clinically Relevant Abnormalities (See Part II ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS).
   2. Abnormal and clinically relevant ECG tracing.
6. Donation or loss of a significant volume of blood or plasma (> 450 mL) within 28 days prior to the initial dose of study medication.
7. Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
8. Allergy or hypersensitivity to letrozole, any of the inactive ingredients.
9. History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption.
10. Consumption of grapefruit or grapefruit containing products within 7 days of drug administration.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Letrozole Tablets 2.5 mg	Drug: Letrozole Tablets 2.5 mg; 2.5mg, single dose fasting
Active Comparator: 2; Femara® Tablets 2.5 mg	Drug: Femara® Tablets 2.5 mg; 2.5mg, single dose fasting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The 90% confidence interval for the LSMeans ratio of CPEAK, AUCL, and AUCI for the test and reference product should be between 80.00% and 125.00% for the natural log-transformed data.	Blood collections through 216 hours

Collaborators and Investigators

• Sponsor: Mylan Pharmaceuticals Inc
• Investigators: Principal Investigator: Lawrence Galitz, M.D., SFBC International

Publications and helpful links

Helpful Links

• Mylan Pharmaceuticals Inc. - Clinical Trial Results
• Daily Med - posting of most recent submitted labelling to the Food and Drug Administration (FDA) and currently in use
• Recalls, Market Withdrawals and Safety Alerts

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: March 30, 2008
• First Submitted That Met QC Criteria: March 31, 2008
• First Posted (Estimate): April 1, 2008

Study Record Updates

• Last Update Posted (Estimate): December 1, 2009
• Last Update Submitted That Met QC Criteria: November 30, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: LETR-05122