ABSORICA in Patients With Severe Recalcitrant Nodular Acne

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.

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.

Eligibility Criteria:
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