Bioequivalence of Two Tacrolimus 0.1% Topical Ointment Formulations in Patients With Atopic Dermatitis

A Randomized, Double-Blind, Placebo Controlled, Parallel Design, Multiple-Site Clinical Study to Evaluate the Bioequivalence of Two Tacrolimus 0.1% Topical Ointment Formulations in Patients With Moderate to Severe Atopic Dermatitis

The primary objectives are to establish the therapeutic equivalence of tacrolimus ointment 0.1%, manufactured by Taro Pharmaceuticals Inc. and Protopic® (tacrolimus), 0.1% topical ointment (Astellas Pharma US, Inc.) and to show superiority over vehicle in the treatment of moderate to severe atopic dermatitis.

The secondary objectives are to compare the adverse event (AE) profiles of the two ointments and to investigate their systemic absorption at steady state.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Tacrolimus 0.1% manufactured by Taro; Drug: Protopic - Tacrolimus 0.1%; Drug: Tacrolimus Vehicle manufactured by Taro

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant, non-lactating female, 18 years of age or older.
• Patient has documented evidence that they have been unresponsive to alternative more traditional therapies such as topical corticosteroids, or in the investigators opinion, such first line therapy would be deemed inadvisable because of potential risks to the patient.
• If female and of child bearing potential, prepare to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., condom, IUD, oral, transdermal, injected or implanted hormonal contraceptives).
• Have confirmed diagnosis of atopic dermatitis using the diagnostic features as described by Hanifin and Rajka.
• Have an IGSA score of 3 (moderate) or 4 (severe)
• Have an affected Body Surface Area (BSA) of at least 20%
• Have a minimum Eczema Area and Severity Index (EASI) score of at least 15

Exclusion Criteria:

• Mild atopic dermatitis as defined by IGSA score of 0 (clear), 1 (almost clear), or 2 (mild) OR %BSA affected less than 20% OR EASI Score of less than 15.
• Clinically infected atopic dermatitis at the baseline visit. Tacrolimus is not indicated for the treatment of clinically infected atopic dermatitis
• Any dermatological condition other than atopic dermatitis that in the Investigator's opinion may interfere with the evaluation of the patient's atopic dermatitis
• Females who are pregnant, lactating or likely to become pregnant during the study.
• History of allergy or sensitivity to tacrolimus, pimecrolimus, any macrolides such as clindamycin erythromycin
• Current diagnosis or history or any disease, which in the Investigators opinion would contraindicate the use of immunosuppressants, including but not limited to human immunodeficiency virus (HIV) and cancer.
• Use of any nonsteroidal immunosuppressants
• Regular use of intranasal or inhaled corticosteroids, greater than the equivalent of 2 mg of prednisone/day, within 14 days of the first dosing day.
• Use of non-sedating histamines are not allowed for at least 7 days prior to the first dosing day or throughout the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tacrolimus 0.1% Taro; Tacrolimus 0.1% manufactured by Taro applied for 14 days	Drug: Tacrolimus 0.1% manufactured by Taro; Treatment applied as a thin layer to target area twice daily for 14 days
Active Comparator: Protopic - Tacrolimus 0.1%; Protopic, Tacrolimus 0.1% applied for 14 days	Drug: Protopic - Tacrolimus 0.1%; Treatment applied as a thin layer to target area twice daily for 14 days
Placebo Comparator: Vehicle; Tacrolimus vehicle applied for 14 days	Drug: Tacrolimus Vehicle manufactured by Taro; Treatment applied as a thin layer to target area twice daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ISGA score 0 or 1	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
% change in BSA	14 days
% change in EASI	14 days
% change in ISGA	14 days
Safety and adverse event profile	14 days

Collaborators and Investigators

• Sponsor: Taro Pharmaceuticals USA

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: January 28, 2009
• First Submitted That Met QC Criteria: January 29, 2009
• First Posted (Estimate): January 30, 2009

Study Record Updates

• Last Update Posted (Estimate): January 22, 2014
• Last Update Submitted That Met QC Criteria: January 19, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Atopic Dermatitis
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: TACR-0707

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No