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

• Sponsor: Galderma R&D (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00660985
• Collaborator: (none)
• Enrollment: 51
• Locations: 2
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 25.5
• Patients Per Site Per Month: 4.2

Study Details

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; 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
• 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 1, 2008
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Nov 1, 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 [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 [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 [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 [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 [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 [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)) [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)) [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)) [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	DermResearch, Inc.	Austin	Texas	United States	78759
2	J&S Studies, Inc.	College Station	Texas	United States	77845

Sponsors and Collaborators

• Galderma R&D

Investigators

• Study Director: Michael Graeber, MD, Galderma R&D

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00660985
• Other Study ID Numbers: RD.06.SPR.18115
• First Posted: Apr 18, 2008
• Last Update Posted: Feb 18, 2021
• Last Verified: Jan 1, 2011

• Keywords provided by , ,: Acne vulgaris; Differin; Adapalene
• Additional relevant MeSH terms: Acne Vulgaris; Adapalene

Study Results

Participant Flow

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Period Title: Overall Study
STARTED	26	25
COMPLETED	25	25
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%	Total
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days	Total of all reporting groups
Overall Participants	26	25	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 100%	25 100%	51 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.4 (4.87)	21.3 (3.78)	22.4 (4.46)
Sex: Female, Male (Count of Participants)
Female	17 65.4%	14 56%	31 60.8%
Male	9 34.6%	11 44%	20 39.2%
Region of Enrollment (participants) [Number]
United States	26 100%	25 100%	51 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (ng/mL) at Day 1
Description	the observed peak drug (adapalene) concentration
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	25	25
Mean (Standard Deviation) [ng/mL]	0.10 (0.10)	0.02 (0.06)

2. Primary Outcome

Title	Cmax (ng/mL) at Day 15
Description	the observed peak drug (adapalene) concentration
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	25	25
Mean (Standard Deviation) [ng/mL]	0.18 (0.09)	0.04 (0.08)

3. Primary Outcome

Title	Cmax (ng/mL) at Day 30
Description	the observed peak drug (adapalene) concentration
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr, T32hr, T36hr, T48hr, T 72hr (post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	25	25
Mean (Standard Deviation) [ng/mL]	0.15 (0.10)	0.03 (0.06)

4. Primary Outcome

Title	Tmax (hr) at Day 1
Description	the time at which Cmax occurs
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)

Outcome Measure Data

Analysis Population Description

26 subjects in the Differin Gel 0.3% and 25 subjects in the Differin Gel 0.1% were included in the study. 14 subjects in the Differin Gel 0.3% and 4 subjects in the Differin Gel 0.1% were detectable at Day 1.

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	14	4
Mean (Standard Deviation) [hours]	15 (6)	11 (4)

5. Primary Outcome

Title	Tmax (hr) at Day 15
Description	the time at which Cmax occurs
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)

Outcome Measure Data

Analysis Population Description

26 subjects in the Differin Gel 0.3% and 25 subjects in the Differin Gel 0.1% were included in the study. 23 subjects in the Differin Gel 0.3% and 7 subjects in the Differin Gel 0.1% were detectable at Day 15.

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	23	7
Mean (Standard Deviation) [hours]	13 (8)	11 (5)

6. Primary Outcome

Title	Tmax (hr) at Day 30
Description	the time at which Cmax occurs
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr, T32hr, T36hr, T48hr, T72hr (post dose)

Outcome Measure Data

Analysis Population Description

26 subjects in the Differin Gel 0.3% and 25 subjects in the Differin Gel 0.1% were included in the study. 20 subjects in the Differin Gel 0.3% and 4 subjects in the Differin Gel 0.1% were detectable at Day 30.

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	20	4
Mean (Standard Deviation) [hours]	13 (6)	12 (3)

7. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 1 (AUC (0-24))
Description	area under the concentration-time curve calculated mixed linear-logarithmic trapezoidal method from pre-application (T0) through 24 hr (corresponding to the dosing interval)
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	25	25
Mean (Standard Deviation) [ng*h/mL]	1.54 (1.58)	0.31 (0.73)

8. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 15 (AUC (0-24))
Description	area under the concentration-time curve calculated mixed linear-logarithmic trapezoidal method from pre-application (T0) through 24hr (corresponding to the dosing interval)
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	24	25
Mean (Standard Deviation) [ng*h/mL]	2.84 (1.75)	0.50 (0.99)

9. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 30 (AUC (0-24))
Description	area under the concentration-time curve calculated mixed linear-logarithmic trapezoidal method from pre-application (T0) through 24hr (corresponding to the dosing interval)
Time Frame	T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr, T32hr, T36hr, T48hr, T72hr (post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Differin® Gel, 0.3%	Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days	Gel, 0.1%, 2g, once daily for 30 days
Measure Participants	25	25
Mean (Standard Deviation) [ng*h/mL]	2.64 (1.66)	0.42 (1.03)

Adverse Events

Arm/Group Title	Differin® Gel, 0.3%		Differin® Gel, 0.1%
Arm/Group Description	Gel, 0.3%, 2g, once daily for 30 days		Gel, 0.1%, 2g, once daily for 30 days
All Cause Mortality
	Differin® Gel, 0.3%		Differin® Gel, 0.1%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Differin® Gel, 0.3%		Differin® Gel, 0.1%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Differin® Gel, 0.3%		Differin® Gel, 0.1%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/26 (11.5%)		2/25 (8%)
Injury, poisoning and procedural complications
Joint sprain	2/26 (7.7%)	2	0/25 (0%)	0
Skin and subcutaneous tissue disorders
Skin irritation	1/26 (3.8%)	1	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.