Pharmacokinetic Study to Compare the Systemic Exposure of Differin® Gel, 0.3% or Differin® Gel, 0.1%

• ClinicalTrials.gov Identifier: NCT00660985
• Recruitment Status: Completed
• First Posted: April 18, 2008
• Results First Posted: December 29, 2009
• Last Update Posted: January 21, 2011
• Sponsor: Galderma
• Information provided by: Galderma

Study Description

Brief Summary:

Phase 4 commitment pharmacokinetic study to determine systemic exposure to adapalene.

Condition or disease	Intervention/treatment	Phase
Acne Vulgaris	Drug: Adapalene	Phase 4

Detailed Description:

Multi-center, double-blind, randomized, parallel group study enrolling male or female subjects with acne vulgaris.

Screening will take place within 14 days prior to Baseline. At the Baseline visit, and at each study day up to Day 30, a trained nurse or technician will apply 2 grams of study medication (either Differin® Gel, 0.3% or Differin® Gel, 0.1%) to the face, upper part of chest, and upper part of back of the subjects. To ensure maximal usage conditions, 2 grams study medication will be applied once daily to a total body surface area of approximately 1000 cm², which is equivalent to 2 mg/cm2.

Subjects will arrive at the clinic the night before on visit days (Day 1, Day 15 and Day 30) when PK blood samples will be drawn. Subjects will be discharged from the clinic on Day 2 and Day 16 following the 24-hour post-dose blood sample, and on Day 31 after the 36-hour post-dose blood samples.

Cutaneous safety (local tolerability assessments) will be assessed, by recording erythema, scaling, dryness, and stinging/burning sensation as separate scores on the face, upper part of the chest, and upper part of the back using a 4-point scale (0 = None to 3 = Severe). Local tolerability assessments will be performed weekly on Day 1, 8, 15, 22 and Day 30, prior application of study medication.

Efficacy will be evaluated by Inflammatory and Non-inflammatory lesion counts on the face performed at Screening, Baseline (Day 1), and on Day 30.

Subjects will have routine laboratory tests (fasting hematology, blood chemistry) performed at Screening and at Day 30 visits.

Blood samples for determination of adapalene plasma concentrations will be drawn on Day 1, Day 15, and Day 30 before the morning study medication application (pre-dose) and 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours after application of study medication; and additionally after the last study medication application (Day 31, 32, 33) at 32, 36, 48 and 72 hours post-dose.

The adapalene plasma concentrations will be determined by a high performance liquid chromatography (HPLC) and fluorescence detection method.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pharmacokinetic Study to Compare the Systemic Exposure to Adapalene During Dermal Application of Either Differin® Gel, 0.3% (Adapalene 0.3%) or Differin® Gel, 0.1% (Adapalene 0.1%) for 30 Days in Subjects With Acne Vulgaris
• Study Start Date: May 2008
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: November 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Differin® Gel, 0.3%; Gel, 0.3%, 2g, once daily for 30 days	Drug: Adapalene; Gel, 0.3%, 2g, once daily for 30 days
Active Comparator: Differin® Gel, 0.1%; Gel, 0.1%, 2g, once daily for 30 days	Drug: Adapalene; Gel, 0.1%, 2g, once daily for 30 days

Outcome Measures

Primary Outcome Measures :

1. Cmax (ng/mL) at Day 1 [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose) ]
   the observed peak drug (adapalene) concentration
2. Cmax (ng/mL) at Day 15 [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose) ]
   the observed peak drug (adapalene) concentration
3. Cmax (ng/mL) at Day 30 [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr, T32hr, T36hr, T48hr, T 72hr (post dose) ]
   the observed peak drug (adapalene) concentration
4. Tmax (hr) at Day 1 [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose) ]
   the time at which Cmax occurs
5. Tmax (hr) at Day 15 [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose) ]
   the time at which Cmax occurs
6. Tmax (hr) at Day 30 [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr, T32hr, T36hr, T48hr, T72hr (post dose) ]
   the time at which Cmax occurs
7. Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 1 (AUC (0-24)) [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose) ]
   area under the concentration-time curve calculated mixed linear-logarithmic trapezoidal method from pre-application (T0) through 24 hr (corresponding to the dosing interval)
8. Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 15 (AUC (0-24)) [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose) ]
   area under the concentration-time curve calculated mixed linear-logarithmic trapezoidal method from pre-application (T0) through 24hr (corresponding to the dosing interval)
9. Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 30 (AUC (0-24)) [ Time Frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr, T32hr, T36hr, T48hr, T72hr (post dose) ]
   area under the concentration-time curve calculated mixed linear-logarithmic trapezoidal method from pre-application (T0) through 24hr (corresponding to the dosing interval)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female 18 to 35 years of age
• Clinical diagnosis of acne vulgaris
• Minimum of 20 Inflammatory
• Minimum of 20 Non-inflammatory lesions
• The subject has a body weight between 45 and 100 kg, and a Body Mass Index (BMI) between 18 and 30Kg/m2

Exclusion Criteria:

• More than 1 nodule or any cyst on the face (excluding the nose)
• Acne conglobata, acne fulminans, secondary acne or severe acne
• Underlying diseases or other dermatological conditions that require the use of interfering topical or systemic therapy
• Pregnant or nursing or planning a pregnancy
• Surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the drug
• Known allergies to any of the ingredients of the study medication
• History of alcohol or drug abuse or positive test results for any drug abuse
• Positive test results for hepatitis B surface antigen (HBs-Ag), hepatitis C virus (HCV) or human immunodeficiency virus antibodies (HIV Ab)
• Use of prohibited medications prior to the study unless appropriate washout period is documented

Contacts and Locations

Locations

United States, Texas

DermResearch, Inc.

Austin,, Texas, United States, 78759

J&S Studies, Inc.

College Station,, Texas, United States, 77845

Sponsors and Collaborators

Galderma

Investigators

• Study Director: Michael Graeber, MD; Galderma

More Information

• Responsible Party: Michael Graeber, MD, Head of US Development:, Galderma R&D
• ClinicalTrials.gov Identifier: NCT00660985
• Other Study ID Numbers: RD.06.SPR.18115
• First Posted: April 18, 2008
• Results First Posted: December 29, 2009
• Last Update Posted: January 21, 2011
• Last Verified: January 2011

Keywords provided by Galderma:

Acne vulgaris; Differin; Adapalene

Additional relevant MeSH terms:

Acne Vulgaris; Acneiform Eruptions; Skin Diseases; Sebaceous Gland Diseases; Adapalene; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Dermatologic Agents