Efficacy and Safety of CIP-Isotretinoin in Patients With Severe Recalcitrant Nodular Acne
Condition: Severe Nodular Acne
MeSH terms: Acne Vulgaris
Intervention: CIP-Isotretinoin; Isotretinoin
Intervention description: 0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.; 0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.
Intervention MeSH terms: Isotretinoin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 925.0
Sex: All
Minimum age: 12 Years
Maximum age: 54 Years
Healthy volunteers: No
Keywords: isotretinoin; dermatology; skin

Summary:

      The purpose of this study is to compare the efficacy and safety of CIP-Isotretinoin and a
      marketed (generic) formulation of isotretinoin when both are administered twice daily with
      meals.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Severe recalcitrant nodular acne, which in the opinion of the investigator is
             compatible with isotretinoin treatment.

          -  Ten (10) or more nodular lesions (facial and/or truncal).

          -  Treatment-naïve patients without any prior exposure to systemic isotretinoin or other
             retinoids.

          -  Age between 12 and 54 years.

          -  Weight between 40 and 110 kg.

          -  Negative serum human chorionic gonadotropin (hCG) pregnancy test consistent with a
             non-pregnant state (females only).

          -  No significant disease or clinically significant finding in a physical examination.

          -  No clinically significant abnormal laboratory value.

          -  No clinically significant abnormal vital sign measurement.

          -  Patients presenting with stable and controlled diabetes mellitus (Types I and II) may
             be included in the study. However, patients should not have had a hospitalization for
             any diabetes related complications in the last 12 months, and must be on stable
             medication for the preceding 6 months. To be included in the study, the patients
             should have Hemoglobin-A1c values ≤ 6.5% at screening and in the test done 3 - 4
             months previously.

          -  Patients with previously diagnosed Polycystic Ovarian Syndrome (PCOS) may be included
             in the study if in the opinion of the investigator they do not have any other
             clinically significant abnormality (e.g. metabolic syndrome or elevated lipids).

        Exclusion Criteria:

          -  Female patients will be excluded from the study if they:

               -  Are pregnant;

               -  Are at high risk for becoming pregnant or likely to become pregnant during
                  treatment;

               -  Will be breast-feeding or considering breast feeding during the course of the
                  study.

          -  Known history or presence of any clinically significant unstable medical condition(s)
             which in the opinion of the investigator could pose a risk for the safety of the
             patient including any previous history of gastrointestinal disease.

          -  Patients with any skin disease or other condition that might interfere with the
             evaluation of recalcitrant nodular acne.

          -  Patients will be interviewed using the SCID-CT current and lifetime modules for Major
             Depression, Mania, and Psychosis. Patients with a lifetime history of psychosis will
             be excluded. Patients with a history of major depressive, manic, hypomanic or mixed
             episodes will not be excluded unless they have had an episode during the preceding
             year.

          -  Patients with any past or current psychotic symptoms.

          -  Patients reporting any suicidal behaviour (including attempts, interrupted attempts,
             aborted attempts, or other preparatory behaviours), within the past year, or serious
             suicidal ideation in the past year, will be excluded from study participation.

          -  A lifetime history of wishing to be dead, non-specific active suicidal thoughts or
             active suicidal ideation without intent to act will not result in exclusion.

          -  Known history or suspected carcinoma.

          -  Known history of liver or kidney disorders (hepatic and renal insufficiency).

          -  Known history or current pseudotumor cerebri (benign intracranial hypertension).

          -  Patients with HLA-B27 related disease, rheumatoid arthritis, rickets or other vitamin
             D depletion disease or phosphate metabolic disease, severe scoliosis > 15 Cobb angle,
             history of back surgery/injuries, ongoing use of anticonvulsants known to affect bone
             metabolism and other genetic or acquired rheumatologic and joint diseases.

          -  All pediatric patients with serum 25-hydroxyvitamin D levels < 20 ng/mL.

          -  Patients with hearing disorders who in the opinion of the investigator would not be
             able to participate in audiometric testing for the study.

          -  Hypersensitivity or idiosyncratic reaction to isotretinoin, Vitamin A and/or any other
             drug substances with similar activity.

          -  Allergy to soy beans, soy bean oil or any other ingredients in the study medications.

          -  On a special diet within four weeks prior to drug administration (e.g., liquid,
             protein, raw food diet).

          -  Difficulty consuming two (2) meals a day to sustain weight and health.