Clinical trial NCT01299610: A Study to Test the Effect of 2 Different Doses of Topical GW870086X on Atopic Dermatitis Also Including a Postive Control and a Placebo
Official title: A Randomised, Double-blind, Placebo-controlled Study of Topical GW870086X Formulation in Subjects With Moderate or Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dermatitis, Atopic
Keywords: Atopic Dermatitis
GW870086X
TIS
IGA
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-02-18
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is a randomised, double-blind, placebo-controlled study to assess the efficacy of GW870086X cream formulation in subjects with moderate to severe atopic dermatitis. Subjects will be assigned to take 3 out of the 4 possible treatments for 21 ±2 days: GW870086X 0.2% cream, GW870086X 2% cream, FP 0.05% cream (as a positive control) and placebo cream. All subjects will be randomised to receive placebo cream. Three index lesions located on the arms and/or legs (one on each) will be identified per subject and each treatment will be applied to the same lesion.

Detailed description: This study is a randomised, double-blind, placebo-controlled study to assess the efficacy of GW870086X cream formulation in subjects with moderate to severe atopic dermatitis. The primary objective of this study is to assess 3 lesions using the Three Item Severity (TIS) score. The secondary objectives are to assess safety and tolerability of GW870086X, assess individual lesions using the Investigators Global Assessment (IGA) and to assess the pharmacokinetics of 21 days dosing of GW870086X administered as a cream. Twenty-five (25) subjects with atopic dermatitis will be randomised to receive placebo and 2 of the following treatments: GW870086X 0.2%, GW870086X 2%, FP 0.05% and placebo. All subjects will receive placebo. Subjects will apply all 3 treatments once daily during the 21 day treatment period. Three index lesions located on the arms and/or legs (one on each) will be identified per subject and each treatment will be applied to the same lesion throughout the 21±2 day treatment period. Each index lesion should represent the most common lesions for each patient i.e. not the most or least severe lesions.

Eligibility criteria: Inclusion Criteria:

* Subjects with a diagnosis of atopic dermatitis who are otherwise healthy.
* Male or female between 18 and 65 years of age inclusive.
* A female subject is eligible to participate if she is of:

  • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the protocol contraception methods if they wish to continue their HRT during the study.
* Male subjects with female partners of child-bearing potential must agree to use one of the protocol contraception methods.
* BMI within the range 19.0 - 29.0 kg/m2 (inclusive).
* Subjects must have body surface area (BSA) disease involvement of \>5% as assessed by the rule of nines method.
* Patients must be willing to refrain from current active therapy for at least 10 days prior to dosing,
* Capable of giving written informed consent.
* Single QTc, QTcB \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
* AST and ALT \< 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

Exclusion Criteria:

* The subject presents with any systemic disorder, active skin disease or subjects who present with scars, moles, tattoos, body piercings, sunburn in the test area which could interfere with the assessment of lesions at screening.
* The subject has atopic dermatitis restricted to the face, the feet or the hands only.
* The subject has a current complication of atopic dermatitis for which treatment with anti-infectives are indicated.
* History of recent (\< 6 months) active or presence of current superficial skin infections of viral aetiology
* The subject has been diagnosed as having contact dermatitis in area of target lesions, seborrheic dermatitis and/or occupational eczema at predilection sites of atopic dermatitis.
* The subject has had topical or transdermal treatments on or near the intended site of application within 14 days prior to first application of study medication.
* The subject has had systemic treatment for atopic dermatitis within 28 days of the first dose of study medication.
* Foreseeable intensive UV exposure during the study. Subjects must not be exposed to direct sunlight or skin tanning devices for the duration of the study.
* The subject has used topical treatment with tar or any corticosteroid within 14 days of the first dose of study medication except topical 1% hydrocortisone which may be used twice daily in patients with severe disease who require step-down therapy during the wash-out period until 3 days prior to study start, after which the hydrocortisone must be discontinued.
* The subject has used topical treatment with buproprion within 14 days of the first dose of study medication.
* History of cutaneous photodisorder.
* History of allergy to steroids or components of test medications.
* History or presence of skin (other than atopic dermatitis), hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
* Subjects with a history of diaphoresis/excessive sweating not restricted to palms or face.
* A positive test for Hepatitis B or Hepatitis C antibody.
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
* A positive pre-study drug/alcohol screen.
* A positive test for HIV antibody.
* History of regular alcohol consumption within 6 months of the study.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* Subject is mentally or legally incapacitated.
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.

Primary outcomes:
measure: Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22
timeFrame: Baseline (Day 1) and Day 22
Secondary outcomes:
measure: Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14
timeFrame: Days 2, 3, 7, and 14
measure: Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22
timeFrame: Days 2, 3, 7, 14 and 22
measure: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Upto Day 21
measure: Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI)
timeFrame: Up to Day 21
measure: Number of Participants With Abnormal Electrocardiogram (ECG) of PCI
timeFrame: Up to Day 21
measure: Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI
timeFrame: Up to Day 21
measure: Pharmacokinetic Parameters: Maximum Observed Concentration (Cmax) of GW870086X
timeFrame: Day 7, 14 and 21
measure: Pharmacokinetic Parameter: Time of Occurrence of Cmax (Tmax) of GW870086
timeFrame: Day 7, 14 and 21
measure: Pharmacokintics Parameter: Area Under Curve (AUC) of GW870086
timeFrame: Day 7, 14 and 21
measure: Pharmacodynamics Endpoint: Skin Thickness and Other Markers of Atopic Dermatitis
timeFrame: Day 1 and Day 22
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: