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
1 other identifier
interventional
925
2 countries
49
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2009
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2009
CompletedFirst Submitted
Initial submission to the registry
September 9, 2009
CompletedFirst Posted
Study publicly available on registry
September 11, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2011
CompletedResults Posted
Study results publicly available
July 4, 2014
CompletedJuly 4, 2014
June 1, 2014
1.7 years
September 9, 2009
July 4, 2012
June 5, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (1)
Proportion of Patients Who Are Rated as Clear/Almost Clear on the Six-point Physicians' Global Assessment Scale (PGSA).
20 weeks
Study Arms (2)
CIP-Isotretinoin
EXPERIMENTALIsotretinoin
ACTIVE COMPARATORInterventions
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.
Eligibility Criteria
You may qualify if:
- 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-naĂ¯ve 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).
You may not qualify if:
- 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.
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (49)
Total Skin & Beauty Dermatology Center
Birmingham, Alabama, 35205, United States
Burke Pharmaceutical Research
Hot Springs, Arkansas, 71913, United States
Center for Dermatology Clinical Research
Fremont, California, 94538, United States
Dermatology Research Associates
Los Angeles, California, 90045, United States
Dermatology Specialists
Oceanside, California, 92056, United States
Skin Surgery Medical Group, Inc.
San Diego, California, 92117, United States
Horizons Clinical Research Center
Denver, Colorado, 80220, United States
North Florida Dermatology Associates, PA
Jacksonville, Florida, 32204, United States
Ameriderm Research
Jacksonville, Florida, 32216, United States
Park Avenue Dermatology
Orange Park, Florida, 32073, United States
Ameriderm Research
Ormond Beach, Florida, 32174, United States
Peachtree Dermatology Associates, PC
Atlanta, Georgia, 30327, United States
MedaPhase Inc.
Newnan, Georgia, 30263, United States
Northwest Clinical Trials
Boise, Idaho, 83704, United States
Northwest Clinical Trials
Nampa, Idaho, 83687, United States
Dawes Fretzin Clinical Research
Indianapolis, Indiana, 46256, United States
The Indiana Clinical Trials Center, PC
Plainfield, Indiana, 46168, United States
The South Bend Clinic, LLP
South Bend, Indiana, 46617, United States
Dermatology and Skin Cancer Specialists / Pediaresearch, LLC
Owensboro, Kentucky, 42303, United States
ActivMed Practices & Research
Haverhill, Massachusetts, 01830, United States
Great Lakes Research Group
Bay City, Michigan, 48706, United States
Hamzavi Dermatology
Fort Gratiot, Michigan, 48059, United States
Minnesota Clinical Study Center
Fridley, Minnesota, 55432, United States
Skin Specialists, PC
Omaha, Nebraska, 68144, United States
Comprehensive Clinical Research
Berlin, New Jersey, 08009, United States
Haber Dermatology, Clinical Research Center
South Euclid, Ohio, 44118, United States
Oregon Dermatology and Research Center
Portland, Oregon, 97210, United States
Paddington Testing Company Inc.
Philadelphia, Pennsylvania, 19103, United States
Radiant Research, Inc.
Greer, South Carolina, 29651, United States
Dermatology Associates of Knoxville
Knoxville, Tennessee, 37934, United States
Tennessee Clinical Research Center
Nashville, Tennessee, 37215, United States
Arlington Center for Dermatology
Arlington, Texas, 76011, United States
Suzanne Bruce and Associates - The Center for Skin Research
Houston, Texas, 77056, United States
Progressive Clinical Research
San Antonio, Texas, 78229, United States
Stephen Miller, MD, PA Dermatology
San Antonio, Texas, 78229, United States
Dermatology Research Center
Salt Lake City, Utah, 84117, United States
Premier Clinical Research
Spokane, Washington, 99204, United States
Derm Research @ 888 Inc.
Vancouver, British Columbia, V5Z 3Y1, Canada
Dermadvances Research
Winnipeg, Manitoba, R3C 1R4, Canada
Durondel C.P. Inc
Moncton, New Brunswick, E1C 8X3, Canada
Newlab Clinical Research Inc.
St. John's, Newfoundland and Labrador, A1C 2H5, Canada
UltraNova Skincare
Barrie, Ontario, L4M 6L2, Canada
Dermatrials Research
Hamilton, Ontario, L8N 1V6, Canada
The Guenther Dermatology Research Centre
London, Ontario, N6A 3H7, Canada
Lynderm Research Inc.
Markham, Ontario, L3P 1A8, Canada
North Bay Dermatology Centre
North Bay, Ontario, P1B 3Z7, Canada
Institute of Cosmetic and Laser Surgery
Oakville, Ontario, L6J 7W5, Canada
K. Papp Clinical Research
Waterloo, Ontario, N2J 1C4, Canada
Windsor Clinical Research
Windsor, Ontario, N8W 5L7, Canada
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Generic isotretinoin control because Accutane® was discontinued in the US. 201 PPP exclusions (CIP-Isotretinoin 101, Isotretinoin 100) due to discontinuation \< Week 20 (61+51), non-compliance with treatment (76+75) or other requirements (≥1 reason).
Results Point of Contact
- Title
- Julia Chan, RAC
- Organization
- Cipher Pharmaceuticals Inc.
Study Officials
- 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.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 9, 2009
First Posted
September 11, 2009
Study Start
September 1, 2009
Primary Completion
May 1, 2011
Study Completion
May 1, 2011
Last Updated
July 4, 2014
Results First Posted
July 4, 2014
Record last verified: 2014-06