Efficacy & Safety Comparison of Epiduo With Doxycycline Versus Vehicle With Isotretinoin in the Treatment of Severe Acne

Study Overview
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Brief Summary
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Non-inferiority, randomized, controlled, multi-center, investigator-blind, parallel-group comparison study in subjects with severe acne vulgaris on the face.

Official Title
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Efficacy and Safety Comparison of Adapalene 0.1% / Benzoyl Peroxide 2.5% Gel Associated With 200 mg Doxycycline Capsules Versus Vehicle Gel Associated With Isotretinoin Capsules in the Treatment of Severe Acne

Conditions
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Acne

Intervention / Treatment
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* Drug: Epiduo/Tactuo
* Other: vehicle gel
* Drug: doxycycline 200mg
* Drug: Isotretinoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject of any race, aged 12 to 35 years inclusive Subject weighing between 50 and 110 kg Subject with severe acne (IGA at least 4), which in the opinion of the investigator is appropriate for treatment with oral isotretinoin (severe nodular acne, severe inflammatory acne, recalcitrant acne; all unresponsive to conventional first line therapies) Subject with at least 5 nodules on the face Exclusion Criteria: Subject with clinically abnormal results to blood testings performed at screening Subject with acne conglobata, acne fulminans, secondary acne (chloracne, drug-induced acne, etc.), pyoderma faciale, sinus tracks Female subject who is pregnant, nursing or planning a pregnancy during the study Subject with known history of hepatic and/or renal insufficiency, to be confirmed by blood testings Subject with known metabolic or structural bone disease (for 12-17 years old population) Subject with bowel disease and/or with hypervitaminosis A Subject who presents with treated or untreated depression or has a history of depression including a family history of major depression Subject with a wash-out period from baseline for topical treatment on the face less than : Corticosteroids, antibiotics, antibacterials, antiseptics, retinoids, other anti-inflammatory drugs or other acne treatments (2 weeks); Cosmetic procedures (1 week); Photodynamic therapy and laser therapy for acne (3 months) Subject with a wash-out period from baseline for systemic treatment less than: Corticosteroids, antibiotics (4 weeks),Progesterone for contraception (3 months); Spironolactone(3 months); Other acne treatments (6 months);Cyproterone acetate(6 months)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epiduo/Tactuo + doxycycline 200mg<br> | Drug: Epiduo/Tactuo<br>* topical to the face, once daily in the evening<br>Drug: doxycycline 200mg<br>* oral, 2 capsules once daily in the morning with aglass of water and with food<br>|
| Active Comparator: Isotretinoin + vehicle gel<br> | Other: vehicle gel<br>* topical to the face, once daily in the evening<br>Drug: Isotretinoin<br>* oral, 0.5mg/kg/day for a period of four weeks, adjusted to 1 mg/kg/day for the four following months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome is Overall Success, a Composite Endpoint Including Efficacy and Safety Measurements | Overall success is reached when the 2 following criteria are fulfilled : Overall efficacy: reduction of at least 75% of number of nodules at the end of treatment Safe treatment: Absence of any listed safety issues | 20 weeks |