Clinical trial NCT00975143: Efficacy and Safety of CIP-Isotretinoin in Patients With Severe Recalcitrant Nodular Acne
Official title: A Double-Blind, Randomized, Phase III, Parallel Group Study Evaluating the Efficacy and Safety of CIP-Isotretinoin in Patients With Severe Recalcitrant Nodular Acne
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Nodular Acne
Keywords: isotretinoin
dermatology
skin
Lead sponsor: Cipher Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2009-09-11
Enrollment: 925
Sex: ALL
Minimum age (years): 12
Maximum age (years): 54
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Co-primary Outcome 1: Change From Baseline in Total Nodular Lesion Count (Facial and Truncal)
timeFrame: 20 weeks
measure: Co-Primary Outcome 2: Proportion of Patients Who Achieve at Least a 90% Reduction in Total Number of Nodular Lesions (Facial and Truncal).
timeFrame: 20 weeks
Secondary outcomes:
measure: Proportion of Patients Who Are Rated as Clear/Almost Clear on the Six-point Physicians' Global Assessment Scale (PGSA).
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Total Skin & Beauty Dermatology Center
state: Alabama
city: Hot Springs
country: United States
facility: Burke Pharmaceutical Research
state: Arkansas
city: Fremont
country: United States
facility: Center for Dermatology Clinical Research
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Oceanside
country: United States
facility: Dermatology Specialists
state: California
city: San Diego
country: United States
facility: Skin Surgery Medical Group, Inc.
state: California
city: Denver
country: United States
facility: Horizons Clinical Research Center
state: Colorado
city: Jacksonville
country: United States
facility: North Florida Dermatology Associates, PA
state: Florida
city: Jacksonville
country: United States
facility: Ameriderm Research
state: Florida
city: Orange Park
country: United States
facility: Park Avenue Dermatology
state: Florida
city: Ormond Beach
country: United States
facility: Ameriderm Research
state: Florida
city: Atlanta
country: United States
facility: Peachtree Dermatology Associates, PC
state: Georgia
city: Newnan
country: United States
facility: MedaPhase Inc.
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Nampa
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research
state: Indiana
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center, PC
state: Indiana
city: South Bend
country: United States
facility: The South Bend Clinic, LLP
state: Indiana
city: Owensboro
country: United States
facility: Dermatology and Skin Cancer Specialists / Pediaresearch, LLC
state: Kentucky
city: Haverhill
country: United States
facility: ActivMed Practices & Research
state: Massachusetts
city: Bay City
country: United States
facility: Great Lakes Research Group
state: Michigan
city: Fort Gratiot
country: United States
facility: Hamzavi Dermatology
state: Michigan
city: Fridley
country: United States
facility: Minnesota Clinical Study Center
state: Minnesota
city: Omaha
country: United States
facility: Skin Specialists, PC
state: Nebraska
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: South Euclid
country: United States
facility: Haber Dermatology, Clinical Research Center
state: Ohio
city: Portland
country: United States
facility: Oregon Dermatology and Research Center
state: Oregon
city: Philadelphia
country: United States
facility: Paddington Testing Company Inc.
state: Pennsylvania
city: Greer
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Knoxville
country: United States
facility: Dermatology Associates of Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Clinical Research Center
state: Tennessee
city: Arlington
country: United States
facility: Arlington Center for Dermatology
state: Texas
city: Houston
country: United States
facility: Suzanne Bruce and Associates - The Center for Skin Research
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Stephen Miller, MD, PA Dermatology
state: Texas
city: Salt Lake City
country: United States
facility: Dermatology Research Center
state: Utah
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Vancouver
country: Canada
facility: Derm Research @ 888 Inc.
state: British Columbia
city: Winnipeg
country: Canada
facility: Dermadvances Research
state: Manitoba
city: Moncton
country: Canada
facility: Durondel C.P. Inc
state: New Brunswick
city: St. John's
country: Canada
facility: Newlab Clinical Research Inc.
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: UltraNova Skincare
state: Ontario
city: Hamilton
country: Canada
facility: Dermatrials Research
state: Ontario
city: London
country: Canada
facility: The Guenther Dermatology Research Centre
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc.
state: Ontario
city: North Bay
country: Canada
facility: North Bay Dermatology Centre
state: Ontario
city: Oakville
country: Canada
facility: Institute of Cosmetic and Laser Surgery
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research
state: Ontario
city: Windsor
country: Canada
facility: Windsor Clinical Research
state: Ontario
Study officials:
affiliation: University of Pennsylvania
name: James J. Leyden, MD
role: STUDY_CHAIR
affiliation: Jefferson Medical College of Thomas Jefferson University
name: Guy Webster, MD
role: STUDY_CHAIR
affiliation: Cipher Pharmaceuticals Inc.
name: Jason A. Gross, PharmD
role: STUDY_DIRECTOR
References: