Acne Vulgaris
Conditions
Keywords
Acne vulgaris, Differin, Adapalene
Brief summary
Phase 4 commitment pharmacokinetic study to determine systemic exposure to adapalene.
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.
Interventions
DRUGAdapalene
Gel, 0.3%, 2g, once daily for 30 days
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Differin® Gel, 0.3% Gel, 0.3%, 2g, once daily for 30 days | 26 |
| Differin® Gel, 0.1% Gel, 0.1%, 2g, once daily for 30 days | 25 |
| Total | 51 |
Baseline characteristics
| Characteristic | Differin® Gel, 0.1% | Differin® Gel, 0.3% | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 26 Participants | 51 Participants |
| Age, Continuous | 21.3 years STANDARD_DEVIATION 3.78 | 23.4 years STANDARD_DEVIATION 4.87 | 22.4 years STANDARD_DEVIATION 4.46 |
| Region of Enrollment United States | 25 participants | 26 participants | 51 participants |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 31 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 26 | 2 / 25 |
| serious Total, serious adverse events | 0 / 26 | 0 / 25 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 15 (AUC (0-24))
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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 15 (AUC (0-24)) | 2.84 ng*h/mL | Standard Deviation 1.75 |
| Differin® Gel, 0.1% | Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 15 (AUC (0-24)) | 0.50 ng*h/mL | Standard Deviation 0.99 |
Primary
Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 1 (AUC (0-24))
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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 1 (AUC (0-24)) | 1.54 ng*h/mL | Standard Deviation 1.58 |
| Differin® Gel, 0.1% | Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 1 (AUC (0-24)) | 0.31 ng*h/mL | Standard Deviation 0.73 |
Primary
Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 30 (AUC (0-24))
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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 30 (AUC (0-24)) | 2.64 ng*h/mL | Standard Deviation 1.66 |
| Differin® Gel, 0.1% | Area Under the Plasma Concentration Versus Time Curve for 0 to 24 Hours Post Dose Measured on Day 30 (AUC (0-24)) | 0.42 ng*h/mL | Standard Deviation 1.03 |
Primary
Cmax (ng/mL) at Day 1
the observed peak drug (adapalene) concentration
Time frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Cmax (ng/mL) at Day 1 | 0.10 ng/mL | Standard Deviation 0.1 |
| Differin® Gel, 0.1% | Cmax (ng/mL) at Day 1 | 0.02 ng/mL | Standard Deviation 0.06 |
Primary
Cmax (ng/mL) at Day 15
the observed peak drug (adapalene) concentration
Time frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Cmax (ng/mL) at Day 15 | 0.18 ng/mL | Standard Deviation 0.09 |
| Differin® Gel, 0.1% | Cmax (ng/mL) at Day 15 | 0.04 ng/mL | Standard Deviation 0.08 |
Primary
Cmax (ng/mL) at Day 30
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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Cmax (ng/mL) at Day 30 | 0.15 ng/mL | Standard Deviation 0.1 |
| Differin® Gel, 0.1% | Cmax (ng/mL) at Day 30 | 0.03 ng/mL | Standard Deviation 0.06 |
Primary
Tmax (hr) at Day 1
the time at which Cmax occurs
Time frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Tmax (hr) at Day 1 | 15 hours | Standard Deviation 6 |
| Differin® Gel, 0.1% | Tmax (hr) at Day 1 | 11 hours | Standard Deviation 4 |
Primary
Tmax (hr) at Day 15
the time at which Cmax occurs
Time frame: T0 (predose), T1hour (hr), T2hr, T4hr, T6 hr, T8 hr, T10hr, T12hr, T16hr, T24hr (post dose)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Tmax (hr) at Day 15 | 13 hours | Standard Deviation 8 |
| Differin® Gel, 0.1% | Tmax (hr) at Day 15 | 11 hours | Standard Deviation 5 |
Primary
Tmax (hr) at Day 30
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Differin® Gel, 0.3% | Tmax (hr) at Day 30 | 13 hours | Standard Deviation 6 |
| Differin® Gel, 0.1% | Tmax (hr) at Day 30 | 12 hours | Standard Deviation 3 |