ABSORICA in Patients With Severe Recalcitrant Nodular Acne

Study Overview
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Brief Summary
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This is an uncontrolled, open-label study being conducted in approximately 200 healthy males, non-pregnant, non-nursing females, age 12 to 45 years, with severe recalcitrant nodular acne. ABSORICA® (isotretinoin) capsules 0.5 mg/kg/day will be administered for 4 weeks followed by 1.0 mg/kg/day for 16 weeks. Female subjects consenting to use two forms of birth control or abstinence are included.

Detailed Description
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This study is designed to collect efficacy, safety, and quality of life (QOL) data from subjects who receive Absorica® without food. The study will investigate the treatment efficacy, frequency of relapse once the treatment has been discontinued, quality of life during the active treatment and during a 2-year post treatment period and the overall safety of treatment with Absorica®. This is a single-arm, open-label study consisting of 2 phases: a 20-week (5-month) open-label Active Treatment Period (ATP) and a 104-week (2-year) post treatment period (PTP). The total study duration is to be 124 weeks, excluding a screening period. During the ATP, after week 2 visit, visits will be scheduled at 4-week intervals for a total of 8 visits (1 screening visit, 1 baseline visit, and 6 on-study visits). During the PTP, the first visit will be 4 weeks after End of Treatment (EOT), the second visit will be 12 weeks after EOT, and subsequent visits will be scheduled at 26-week (± 2 weeks) intervals for a total of 6 visits.

Official Title
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An Open-label Study Evaluating the Long-term Efficacy, Quality of Life, and Safety of ABSORICA® (Isotretinoin) Capsules Administered Without Food in Patients With Severe Recalcitrant Nodular Acne

Conditions
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Acne

Intervention / Treatment
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* Drug: Isotretinoin


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria Subjects must meet the following mandatory inclusion criteria at the time of screening to be eligible to enter the study and must agree to conform to the requirements of the study and the iPLEDGE program. Written informed consent, including mandatory photographic consent, on a gender-specific informed consent form (ICF) & Health Insurance Portability and Accountability Act (HIPAA) authorization prior to the performance of any study-related procedures. Pregnant females and females who are not to become pregnant during the ATP phase of the trial and for 30 days after receiving their last dose of study drug. Female subjects of childbearing potential ready to use 2 forms of effective contraception simultaneously for 1 month before starting Absorica® (isotretinoin), while taking Absorica® & for 1 month after Absorica® has been stopped. Male and female subjects of non-childbearing potential Specific Inclusion Criteria: Severe recalcitrant nodular acne. Five or more nodule lesions on the face. Treatment-naïve subjects. Age between 12 and 45 years. Weight between 40 and 110 kg. Female subjects of childbearing potential only: Negative results from serum pregnancy tests with a sensitivity of at least 25 milli-international unit/mL. Good general health as determined by the investigator based on the subject's medical history, physical examination, vital signs measurements, and laboratory test results. Subjects who present with stable & controlled diabetes mellitus (Types I and II). Subjects with previously diagnosed polycystic ovarian syndrome (PCOS) can be included in the study if in the opinion of the investigator they do not have any other clinically significant abnormality (eg, metabolic syndrome or elevated lipids Exclusion Criteria: General Exclusion Criteria Presence of any clinically significant physical examination finding, vital signs measurement, or abnormal laboratory value; Presence of a beard or other facial hair that could interfere with the study assessments; Participated in another clinical trial or received an investigational product within 3 months prior to screening; History of excessive or suspected abuse of alcohol (based on the clinical judgment of the investigator), recreational drugs, and/or drugs of abuse, e.g., club drugs, cocaine, ecstasy/ methylenedioxymethamphetamine, heroin, inhalants, marijuana, methamphetamine, phencyclidine, prescription medications, anabolic steroids, etc. Use of prohibited or restricted prior or concomitant medications. Female Specific Exclusion Criteria Are pregnant; Are at a high risk for becoming pregnant or likely to become pregnant during treatment; Are breast-feeding or considering breast-feeding during the course of the study; Have a known history of PCOS with another clinically significant abnormality (eg, metabolic syndrome or elevated lipids); Are unable or unwilling to maintain compliance with birth control measures

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 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: Single treatment arm<br>ABSORICA® (isotretinoin) capsules 0.5 mg/kg/day for 4 weeks followed by 1.0 mg/kg/day for 16 weeks. | Drug: Isotretinoin<br>* ABSORICA® (isotretinoin) capsules 0.5 mg/kg/day for 4 weeks followed by 1.0 mg/kg/day for 16 weeks<br>* Other names: ABSORICA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active Treatment Period: Total Acne-Specific Quality of Life Score at Week 20 | There are 4 domains: self-perception (22 questions), role-social (50 questions), role-emotional (33 questions), and acne symptoms (85 questions) in the acne-QOL questionnaires. Calculation of the domain scores was accomplished by summing all item responses within each domain. Self-perception: The range of possible scores is 0 to 30 points. Role-social: The range of possible scores is 0 to 24 points. Role emotional: The domain scores range from 0 to 30 points. Acne symptoms: The domain scores range from 0 to 30 points. | Week 20 | 
| Primary Efficacy Endpoint, Post-treatment Period: Subjects Requiring Retreatment During the Post-treatment Period and Time to Retreatment | subjects who were at least 75% compliant with their assigned treatment, had no major protocol violations, had a Week 20 count of total nodular lesions, and did not use any disallowed medications during the 20 weeks of treatment. (Retreated with Oral Isotretinoin Per Protocol Population). | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active Treatment Period- Change From Baseline in Lesion Counts at Week 20 | Change from baseline in the lesion count (nodules and inflammatory lesions) at the end of the ATP. (Per Protocol Population) | Baseline and at week 20 | 
| Active Treatment Period-Change From Baseline in Acne-Specific Quality of Life Total Score at Weeks 4, 8, 12, and 16 | There are 4 domains: self-perception (22 questions), role-social (50 questions), role-emotional (33 questions), and acne symptoms (85 questions) in the acne-QOL questionnaires. Calculation of the domain scores was accomplished by summing all item responses within each domain. Self-perception: The range of possible scores is 0 to 30 points. Role-social: The range of possible scores is 0 to 24 points. Role emotional: The domain scores range from 0 to 30 points. Acne symptoms: The domain scores range from 0 to 30 points. | Baseline, at week 4, week 8, week 12, and week16 | 
| Active Treatment Period- Investigator's Global Assessment at Week 20 | Investigator's Global Assessment score: 0 = Clear = Almost Clear = Mild = Moderate = Severe = Very Severe | week 20 | 
| Active Treatment Period- Change From Baseline in Acne-Specific Quality of Life Domain Scores by Domain at Weeks 4, 8, 12, and 16 | Acne-Specific Quality of Life, by domain: Self Perception: response on 0- to 6-point scale; the range of possible scores is 0 to 30 points. Role-social: response on 0- to 6-point scale; the range of possible scores is 0 to 24 points. Role-emotional: response on 0- to 6-point scale, exactly the same as those used for the Self Perception and Role-social domains. Acne Symptoms:response on 0- to 6-point scale, domain scores range from 0 to 30 points | 20 weeks | 
| Active Treatment Period- Change From Baseline in Nodule Count at Week 20 |  | Baseline, and at week20 | 
| Post-treatment Period- Proportion of Subjects Requiring Treatment With Anti-Acne Medication and Time to Retreatment | Retreated with Prescription Anti-Acne Medication, n/Na (%); Over-the-Counter Anti-Acne Medication and Prescription or Over-the-Counter Anti-Acne Medication- Per Protocol Population. | 104 weeks | 
| Post-treatment Period- Severity of Acne by Lesion Count at Time of Retreatment With Oral Isotretinoin | change from Baseline | 104 weeks | 
| Post-treatment Period- Severity of Acne by Investigator's Global Assessment at Time of Retreatment With Oral Isotretinoin | Investigator's Global Assessment score: 0 = Clear = Almost Clear = Mild = Moderate = Severe = Very Severe | 104 weeks | 
| Post-treatment Period- Severity of Acne by Lesion Count at Time of Retreatment With Prescription Other Than Oral Isotretinoin | Change from baseline | 104 weeks | 
| Post-treatment Period- Severity of Acne by Investigator's Global Assessment Score at Time of Retreatment With Over-the-Counter Medication | Investigator's Global Assessment score: 0 = Clear = Almost Clear = Mild = Moderate = Severe = Very Severe | 20 weeks | 
| Post-treatment Period-Severity of Acne by Lesion Count at Each Visit During the Post-treatment Period |  | week 124 | 
| Post Treatment Period- Severity of Acne by Nodule Count at Each Visit During the Post-treatment Period | Change from Baseline-Week 124 | week 124 | 
| Severity of Acne by Investigator's Global Assessment Score at Each Visit During the Post-treatment Period | Investigator's Global Assessment score: 0 = Clear = Almost Clear = Mild = Moderate = Severe = Very Severe | week 124 | 
| Post-treatment Period- Severity of Acne by Lesion Count at Time of Retreatment With Over-the-Counter Medications | Change from Baseline | 20 weeks | 
| Post Treatment Period-Severity of Acne by Investigator's Global Assessment Score at Time of Retreatment With Prescription Other Than Oral Isotretinoin | Investigator's Global Assessment score: 0 = Clear = Almost Clear = Mild = Moderate = Severe = Very Severe | 20 weeks |