A Treatment for Severe Inflammatory Acne Subjects

Study Overview
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Brief Summary
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Demonstrate that a daily treatment regimen of adapalene 0.3%/benzoyl peroxide 2.5% gel + oral Doxycycline 200 mg is effective and safe in severe inflammatory acne with 3 or fewer nodules or cysts (non-nodulocystic) during a 12-week treatment period.

Detailed Description
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This Phase 4, 12-week, single-arm, open-label, multi-center investigational efficacy and safety study was conducted in subjects with severe inflammatory acne. Subjects who met the inclusion criteria and none of the exclusion criteria at the Screening visit returned to the clinic for baseline measures (Week 0) and to start treatment, which continued for up to 12 weeks. Treatment consisted of 2 investigational study drugs: A/BPO 0.3%/2.5% gel applied to dry skin as directed by study staff once daily for 12 weeks, at night after washing. Doxycycline hyclate 200 mg: each subject was to take 2 50-mg tablets of doxycycline hyclate in the morning and 2 at night, for a total of 4 tablets (a total of 200 mg) daily for 12 weeks.

Official Title
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Efficacy and Safety of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Doxycycline in Severe Inflammatory Acne (Non-Nodulocystic) Subjects

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Adapalene 0.3% / benzoyl peroxide 2.5% emulsion gel
* Drug: Oral doxycycline hyclate


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subjects, 12 years of age or older at Screening visit. Subjects with a clinical diagnosis of severe inflammatory acne (IGA score of 4). Subjects with 4 or fewer nodules or cysts > 1 cm in diameter on the face. Subjects 18 years of age or older must read and sign the Informed Consent Form, which includes Photography Consent and HIPAA authorization, prior to any participation in the study. Consent will be obtained prior to any study-related procedures. Subjects under the age of 18 years must sign an Assent to Participate Form to participate in the study and must have one parent or guardian read and sign the Informed Consent Form prior to any study-related procedure. (The parent or guardian is not required to attend the following visits unless requested.) Key Exclusion Criteria: Subjects with nodulocystic or conglobate acne, acne fulminans, or secondary acne (chloracne, drug-induced acne, etc.). Subjects with 5 or more acne nodules or cysts > 1 cm in diameter on the face at Screening and Baseline visits. Female subjects who are pregnant, nursing, or planning a pregnancy during the study. Subjects who have used any systemic therapy directed at improving acne, including antibiotics, within 30 days prior to Baseline visit. Subjects who are at risk in terms of precautions, warnings, and contraindications for the investigational study drugs (see Appendix 14.1 for package inserts for adapalene 0.3%/benzoyl peroxide 2.5% gel and doxycycline hyclate Tablets). Subjects with any other condition or circumstance which, in the Investigator's opinion, may put the subject at risk (e.g., a history of significant renal disease with impairment of renal function), confound the study results, or interfere with the subject's participation in the study. Sponsor and study site staff, relatives of staff members, or other individuals who would have access to the clinical study protocol.

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acne treatment<br>Topical adapalene 0.3% / benzoyl peroxide 2.5% emulsion gel (one application daily for 12 weeks) Oral doxycycline hyclate, 200 mg per day (two 50-mg tablets twice daily for 12 weeks) | Drug: Adapalene 0.3% / benzoyl peroxide 2.5% emulsion gel<br>* Topical acne therapy<br>* Other names: Epiduo Forte;Drug: Oral doxycycline hyclate<br>* Tetracycline-class oral antibacterial 200 mg daily (2 tablets [50 mg], twice daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Number of Inflammatory Lesions | Change in Number of Inflammatory Lesions from baseline. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percent of Subjects With IGA Success | IGA Success is defined as an IGA rating of Clear (Grade 0) or Almost Clear (Grade 1) | Weeks 4, 8, and 12 | 
| Percent Change From Baseline in Total Lesion Count | Percent Change From Baseline in Total Lesion Count. | Weeks 4, 8, and 12 | 
| Change From Baseline in Total Lesion Count | Change From Baseline in Total Lesion Count. | Weeks 4, 8, and 12 | 
| Percent Change From Baseline in Inflammatory Lesion Count | Percent Change From Baseline in Inflammatory Lesion Count. | Weeks 4, 8, and 12 | 
| Change From Baseline in Inflammatory Lesion Count | Change From Baseline in Inflammatory Lesion Count. | Weeks 4, 8, and 12 | 
| Percent Change From Baseline in Non-Inflammatory Lesion Count | Percent Change From Baseline in Non-Inflammatory Lesion Count. | Weeks 4, 8, and 12 | 
| Change From Baseline in Non-Inflammatory Lesion Count | Change From Baseline in Non-Inflammatory Lesion Count. | Weeks 4, 8, and 12 | 
| Investigator's Evaluation: Number of Subjects Not Considered to be Oral Isotretinoin Candidates | At each visit, subjects were evaluated by the investigator to determine whether (in the opinion of the investigator) they would consider them as candidates for oral isotretinoin therapy. The outcome measure reports the number and % of subjects who, in the opinion of the investigator, were not considered to be a candidate for oral isotretinoin therapy. | Weeks 0, 4, 8, and 12 | 
| Subject Assessment of Acne Improvement | Subject Assessment of Acne Improvement on a 6 point scale (0 = Complete Improvement, 1 = Marked Improvement, 2 = Moderate Improvement, 3 = Minimal Improvement, 4 = No Change, 5 = Worse). | Week 12 | 
| Number and Percent of Adverse Events | Number and percent of subjects with any Treatment-Related Adverse Event | Week 12 |