Severe Nodular AcnePhase 3NCT00975143

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

A Phase 3 study testing CIP-Isotretinoin and Isotretinoin in people with Severe Nodular Acne, run by Cipher Pharmaceuticals Inc. at 49 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 12 to 54 years
Conditions the study is for: Severe Nodular Acne
What is being tested?: CIP-Isotretinoin and Isotretinoin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 925 participants
Where: 49 sitesin 2 countries
Study dates: Sep 2009to May 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 54 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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).

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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).

Who cannot join

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.

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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.

Trial locations and contacts

49 sites in 2 countries.

Country

City, postcode or hospital

49 sites in 2 countries

United States37 sites

Arlington Center for Dermatology
Arlington, Texas, 76011
Peachtree Dermatology Associates, PC
Atlanta, Georgia, 30327
Great Lakes Research Group
Bay City, Michigan, 48706
Comprehensive Clinical Research
Berlin, New Jersey, 08009
Total Skin & Beauty Dermatology Center
Birmingham, Alabama, 35205
Northwest Clinical Trials
Boise, Idaho, 83704
Horizons Clinical Research Center
Denver, Colorado, 80220
Hamzavi Dermatology
Fort Gratiot, Michigan, 48059
Center for Dermatology Clinical Research
Fremont, California, 94538
Minnesota Clinical Study Center
Fridley, Minnesota, 55432
Radiant Research, Inc.
Greer, South Carolina, 29651
ActivMed Practices & Research
Haverhill, Massachusetts, 01830
Burke Pharmaceutical Research
Hot Springs, Arkansas, 71913
Suzanne Bruce and Associates - The Center for Skin Research
Houston, Texas, 77056
Dawes Fretzin Clinical Research
Indianapolis, Indiana, 46256
North Florida Dermatology Associates, PA
Jacksonville, Florida, 32204
Ameriderm Research
Jacksonville, Florida, 32216
Dermatology Associates of Knoxville
Knoxville, Tennessee, 37934
Dermatology Research Associates
Los Angeles, California, 90045
Northwest Clinical Trials
Nampa, Idaho, 83687
Tennessee Clinical Research Center
Nashville, Tennessee, 37215
MedaPhase Inc.
Newnan, Georgia, 30263
Dermatology Specialists
Oceanside, California, 92056
Skin Specialists, PC
Omaha, Nebraska, 68144
Park Avenue Dermatology
Orange Park, Florida, 32073
Ameriderm Research
Ormond Beach, Florida, 32174
Dermatology and Skin Cancer Specialists / Pediaresearch, LLC
Owensboro, Kentucky, 42303
Paddington Testing Company Inc.
Philadelphia, Pennsylvania, 19103
The Indiana Clinical Trials Center, PC
Plainfield, Indiana, 46168
Oregon Dermatology and Research Center
Portland, Oregon, 97210
Dermatology Research Center
Salt Lake City, Utah, 84117
Progressive Clinical Research
San Antonio, Texas, 78229
Stephen Miller, MD, PA Dermatology
San Antonio, Texas, 78229
Skin Surgery Medical Group, Inc.
San Diego, California, 92117
The South Bend Clinic, LLP
South Bend, Indiana, 46617
Haber Dermatology, Clinical Research Center
South Euclid, Ohio, 44118
Premier Clinical Research
Spokane, Washington, 99204

Other trials in United States

Canada12 sites

UltraNova Skincare
Barrie, Ontario, L4M 6L2
Dermatrials Research
Hamilton, Ontario, L8N 1V6
The Guenther Dermatology Research Centre
London, Ontario, N6A 3H7
Lynderm Research Inc.
Markham, Ontario, L3P 1A8
Durondel C.P. Inc
Moncton, New Brunswick, E1C 8X3
North Bay Dermatology Centre
North Bay, Ontario, P1B 3Z7
Institute of Cosmetic and Laser Surgery
Oakville, Ontario, L6J 7W5
Newlab Clinical Research Inc.
St. John's, Newfoundland and Labrador, A1C 2H5
Derm Research @ 888 Inc.
Vancouver, British Columbia, V5Z 3Y1
K. Papp Clinical Research
Waterloo, Ontario, N2J 1C4
Windsor Clinical Research
Windsor, Ontario, N8W 5L7
Dermadvances Research
Winnipeg, Manitoba, R3C 1R4

Other trials in Canada

About this study

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

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.

Conditions: Severe Nodular Acne
Being tested: CIP-Isotretinoin, Isotretinoin
Keywords: isotretinoin, dermatology, skin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CIP-IsotretinoinDrug
0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.
IsotretinoinDrug
0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.

Study groups in NCT00975143
Study group	Role	What they receive
CIP-Isotretinoin	Experimental	Not described Receives: Drug: CIP-Isotretinoin
Isotretinoin	Active comparator	Not described Receives: Drug: Isotretinoin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 20 weeks

Secondary outcomes (1)

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.
Measured: 20 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2009May 2011

First posted11 Sep 2009 (estimated)
Study startSep 2009
Primary completionMay 2011
Study completionMay 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Severe Nodular AcneStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 925 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00975143
Sponsor's protocol ID: ISOCT.08.01
Status last verified: Jun 2014
First submitted: 9 Sep 2009
Last updated: 4 Jul 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Study at a glance

From the registry record, last updated by the sponsor on 4 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00975143
Acronym / sponsor ID: ISOCT.08.01
Conditions: Severe Nodular Acne
Keywords: isotretinoin, dermatology, skin
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 925 participants (actual)
Lead sponsor: Cipher Pharmaceuticals Inc.Industry (pharma, biotech, devices)
Study start: Sep 2009
Primary completion: May 2011 (actual)
Study completion: May 2011 (actual)
First posted: 11 Sep 2009 (estimated)
Results: Posted 4 Jul 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
CIP-Isotretinoin	Experimental	Drug: CIP-Isotretinoin
Isotretinoin	Active comparator	Drug: Isotretinoin

Who may qualify

Ages: 12 to 54 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (11 listed)

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.

Key exclusion criteria (20 listed)

Female patients will be excluded from the study if they:
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CIP-Isotretinoin0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.	Drug	CIP-Isotretinoin
Isotretinoin0.5 mg/kg/day for 4 weeks, and 1 mg/kg/day for 16 weeks, taken orally, twice daily.	Drug	Isotretinoin

Primary outcome

Co-primary Outcome 1: Change From Baseline in Total Nodular Lesion Count (Facial and Truncal)
Time frame: 20 weeks
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.
Co-Primary Outcome 2: Proportion of Patients Who Achieve at Least a 90% Reduction in Total Number of Nodular Lesions (Facial and Truncal).
Time frame: 20 weeks
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.

1 secondary outcome

Proportion of Patients Who Are Rated as Clear/Almost Clear on the Six-point Physicians' Global Assessment Scale (PGSA).
Time frame: 20 weeks

Results and safety

Results posted to the registry on 4 Jul 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CIP-Isotretinoin	464	394
Isotretinoin	461	401

Primary outcome: Co-primary Outcome 1: Change From Baseline in Total Nodular Lesion Count (Facial and Truncal)

Time frame: 20 weeks. Mean (Standard Deviation). Unit: Lesions

Measure	CIP-Isotretinoin n = 363	Isotretinoin n = 361
Value	-17.01 (14.26)	-16.52 (10.57)

CIP-Isotretinoin vs Isotretinoin: LS Mean Difference: 0.1382 (95% CI -0.2712 to 0.5475), p = 0.5077, ANCOVA

Population analysed: Analysis based on the Per Protocol (PP) Population, defined as all randomized patients who were at least 75% compliant with their assigned treatment, had no major study protocol violations, had a Week 20 count of total nodular lesions, and did not use any disallowed medications during the 20 study weeks.

Primary outcome: Co-Primary Outcome 2: Proportion of Patients Who Achieve at Least a 90% Reduction in Total Number of Nodular Lesions (Facial and Truncal).

Time frame: 20 weeks. Number (95% Confidence Interval). Unit: percentage of participants

Measure	CIP-Isotretinoin n = 363	Isotretinoin n = 361
Value	78.8 (74.6 to 83.0)	80.9 (76.8 to 84.9)

CIP-Isotretinoin vs Isotretinoin: Proportion difference: -2.10 (95% CI -7.94 to 3.74), p >0.05, Normal approximation

1 secondary outcome is reported in the full results.

Adverse events

Time frame: AEs and SAEs were collected from the beginning of double-blind treatment until 30 days after the last study treatment (Week 24). AEs occurring before starting study treatment but after signing the informed consent form were recorded under Medical History.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CIP-Isotretinoin	7 of 464 (1.5%)	428 of 464 (92.2%)	Not reported
Isotretinoin	5 of 460 (1.1%)	413 of 460 (89.8%)	Not reported

Limitations and caveats (from the sponsor): 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).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James J. Leyden, MD study chair

University of Pennsylvania

Guy Webster, MD study chair

Jefferson Medical College of Thomas Jefferson University

Jason A. Gross, PharmD study director

Cipher Pharmaceuticals Inc.

49 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CIP-Isotretinoin and Isotretinoin in people with Severe Nodular Acne, run by Cipher Pharmaceuticals Inc. at 49 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Co-primary Outcome 1: Change From Baseline in Total Nodular Lesion Count (Facial and Truncal) (time frame: 20 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00975143.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jul 2014.