Efficacy and Safety of CIP-Isotretinoin in Patients With Severe Recalcitrant Nodular Acne

A Double-Blind, Randomized, Phase III, Parallel Group Study Evaluating the Efficacy and Safety of CIP-Isotretinoin in Patients With Severe Recalcitrant Nodular Acne

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.

Study Overview

• Status: Completed
• Conditions: Severe Nodular Acne
• Intervention / Treatment: Drug: CIP-Isotretinoin; Drug: Isotretinoin

• Study Type: Interventional
• Enrollment (Actual): 925
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3Y1
      • Derm Research @ 888 Inc.
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 1R4
      • Dermadvances Research
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Durondel C.P. Inc
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1C 2H5
      • NewLab Clinical Research Inc.
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Ultranova Skincare
    • Hamilton, Ontario, Canada, L8N 1V6
      • Dermatrials Research
    • London, Ontario, Canada, N6A 3H7
      • The Guenther Dermatology Research Centre
    • Markham, Ontario, Canada, L3P 1A8
      • Lynderm Research Inc.
    • North Bay, Ontario, Canada, P1B 3Z7
      • North Bay Dermatology Centre
    • Oakville, Ontario, Canada, L6J 7W5
      • Institute of Cosmetic and Laser Surgery
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
    • Windsor, Ontario, Canada, N8W 5L7
      • Windsor Clinical Research
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Total Skin & Beauty Dermatology Center
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Burke Pharmaceutical Research
  • California
    • Fremont, California, United States, 94538
      • Center for Dermatology Clinical Research
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Oceanside, California, United States, 92056
      • Dermatology Specialists
    • San Diego, California, United States, 92117
      • Skin Surgery Medical Group, Inc.
  • Colorado
    • Denver, Colorado, United States, 80220
      • Horizons Clinical Research Center
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Ameriderm Research
    • Jacksonville, Florida, United States, 32204
      • North Florida Dermatology Associates, PA
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology
    • Ormond Beach, Florida, United States, 32174
      • Ameriderm Research
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Peachtree Dermatology Associates, PC
    • Newnan, Georgia, United States, 30263
      • MedaPhase Inc.
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials
    • Nampa, Idaho, United States, 83687
      • Northwest Clinical Trials
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research
    • Plainfield, Indiana, United States, 46168
      • The Indiana Clinical Trials Center, PC
    • South Bend, Indiana, United States, 46617
      • The South Bend Clinic, LLP
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Dermatology and Skin Cancer Specialists / Pediaresearch, LLC
  • Massachusetts
    • Haverhill, Massachusetts, United States, 01830
      • ActivMed Practices & Research
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group
    • Fort Gratiot, Michigan, United States, 48059
      • Hamzavi Dermatology
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Clinical Study Center
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Skin Specialists, PC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
  • Ohio
    • South Euclid, Ohio, United States, 44118
      • Haber Dermatology, Clinical Research Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Company Inc.
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Radiant Research, Inc.
  • Tennessee
    • Knoxville, Tennessee, United States, 37934
      • Dermatology Associates of Knoxville
    • Nashville, Tennessee, United States, 37215
      • Tennessee Clinical Research Center
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Center for Dermatology
    • Houston, Texas, United States, 77056
      • Suzanne Bruce and Associates - The Center for Skin Research
    • San Antonio, Texas, United States, 78229
      • Progressive Clinical Research
    • San Antonio, Texas, United States, 78229
      • Stephen Miller, MD, PA Dermatology
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Dermatology Research Center
  • Washington
    • Spokane, Washington, United States, 99204
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 52 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CIP-Isotretinoin	Drug: CIP-Isotretinoin; 0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.
Active Comparator: Isotretinoin	Drug: Isotretinoin; 0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-primary Outcome 1: Change From Baseline in Total Nodular Lesion Count (Facial and Truncal)	The change from Baseline to Week 20 in the total number of nodular lesions was calculated as the Week 20 lesion count minus Baseline lesion count and compared using Analysis of Covariance (ANCOVA), controlling for Baseline total nodular lesion count, gender and analysis site. The 95% CI of the adjusted least square mean difference (CIP-ISOTRETINOIN minus Isotretinoin) was also calculated using the ANCOVA model. Pre-defined criterion for non-inferiority: upper bound of the 95% CI for the treatment difference < 4.	20 weeks
Co-Primary Outcome 2: Proportion of Patients Who Achieve at Least a 90% Reduction in Total Number of Nodular Lesions (Facial and Truncal).	The percentage of patients in each group who achieved ≥90% reduction in the total nodular lesion count from Baseline to Week 20 was calculated along with its 95% CI (normal approximation). A 95% 2-sided CI on the difference between treatments (CIP-ISOTRETINOIN minus Isotretinoin) was also computed. Pre-defined criterion for non-inferiority: lower bound of the 95% CI for the treatment difference > -10.	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Who Are Rated as Clear/Almost Clear on the Six-point Physicians' Global Assessment Scale (PGSA).	PGSA categories: 1 (Almost clear); 2 (Mild); 3 (Moderate); 4 (Severe); 5 (Very severe). A grade of either 0 (clear) or 1 (almost clear) on the 6-point PGSA scale within the Week 20 analysis window was considered a success.	20 weeks

Collaborators and Investigators

• Sponsor: Cipher Pharmaceuticals Inc.
• Investigators: Study Chair: James J. Leyden, MD, University of Pennsylvania; Study Chair: Guy Webster, MD, Jefferson Medical College of Thomas Jefferson University; Study Director: Jason A. Gross, PharmD, Cipher Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 9, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (Estimate): September 11, 2009

Study Record Updates

• Last Update Posted (Estimate): July 4, 2014
• Last Update Submitted That Met QC Criteria: June 5, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: skin; dermatology; isotretinoin
• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Acne Vulgaris; Dermatologic Agents; Isotretinoin
• Other Study ID Numbers: ISOCT.08.01