ABSORICA in Patients With Severe Recalcitrant Nodular Acne

An Open-label Study Evaluating the Long-term Efficacy, Quality of Life, and Safety of ABSORICA® (Isotretinoin) Capsules Administered Without Food in Patients With Severe Recalcitrant Nodular Acne

This is an uncontrolled, open-label study being conducted in approximately 200 healthy males, non-pregnant, non-nursing females, age 12 to 45 years, with severe recalcitrant nodular acne.

ABSORICA® (isotretinoin) capsules 0.5 mg/kg/day will be administered for 4 weeks followed by 1.0 mg/kg/day for 16 weeks. Female subjects consenting to use two forms of birth control or abstinence are included.

Study Overview

• Status: Completed
• Conditions: Acne
• Intervention / Treatment: Drug: Isotretinoin

Detailed Description

This study is designed to collect efficacy, safety, and quality of life (QOL) data from subjects who receive Absorica® without food. The study will investigate the treatment efficacy, frequency of relapse once the treatment has been discontinued, quality of life during the active treatment and during a 2-year post treatment period and the overall safety of treatment with Absorica®.

This is a single-arm, open-label study consisting of 2 phases: a 20-week (5-month) open-label Active Treatment Period (ATP) and a 104-week (2-year) post treatment period (PTP). The total study duration is to be 124 weeks, excluding a screening period. During the ATP, after week 2 visit, visits will be scheduled at 4-week intervals for a total of 8 visits (1 screening visit, 1 baseline visit, and 6 on-study visits). During the PTP, the first visit will be 4 weeks after End of Treatment (EOT), the second visit will be 12 weeks after EOT, and subsequent visits will be scheduled at 26-week (± 2 weeks) intervals for a total of 6 visits.

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78218
      • Texas Dermatology and Laser Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

General Inclusion Criteria Subjects must meet the following mandatory inclusion criteria at the time of screening to be eligible to enter the study and must agree to conform to the requirements of the study and the iPLEDGE program.

• Written informed consent, including mandatory photographic consent, on a gender-specific informed consent form (ICF) & Health Insurance Portability and Accountability Act (HIPAA) authorization prior to the performance of any study-related procedures.
• Pregnant females and females who are not to become pregnant during the ATP phase of the trial and for 30 days after receiving their last dose of study drug.
• Female subjects of childbearing potential ready to use 2 forms of effective contraception simultaneously for 1 month before starting Absorica® (isotretinoin), while taking Absorica® & for 1 month after Absorica® has been stopped.
• Male and female subjects of non-childbearing potential

Specific Inclusion Criteria:

• Severe recalcitrant nodular acne.
• Five or more nodule lesions on the face.
• Treatment-naïve subjects.
• Age between 12 and 45 years.
• Weight between 40 and 110 kg.
• Female subjects of childbearing potential only: Negative results from serum pregnancy tests with a sensitivity of at least 25 milli-international unit/mL.
• Good general health as determined by the investigator based on the subject's medical history, physical examination, vital signs measurements, and laboratory test results.
• Subjects who present with stable & controlled diabetes mellitus (Types I and II).
• Subjects with previously diagnosed polycystic ovarian syndrome (PCOS) can be included in the study if in the opinion of the investigator they do not have any other clinically significant abnormality (eg, metabolic syndrome or elevated lipids

Exclusion Criteria:

General Exclusion Criteria

• Presence of any clinically significant physical examination finding, vital signs measurement, or abnormal laboratory value;
• Presence of a beard or other facial hair that could interfere with the study assessments;
• Participated in another clinical trial or received an investigational product within 3 months prior to screening;
• History of excessive or suspected abuse of alcohol (based on the clinical judgment of the investigator), recreational drugs, and/or drugs of abuse, e.g., club drugs, cocaine, ecstasy/ methylenedioxymethamphetamine, heroin, inhalants, marijuana, methamphetamine, phencyclidine, prescription medications, anabolic steroids, etc.
• Use of prohibited or restricted prior or concomitant medications. Female Specific Exclusion Criteria
• Are pregnant;
• Are at a high risk for becoming pregnant or likely to become pregnant during treatment;
• Are breast-feeding or considering breast-feeding during the course of the study;
• Have a known history of PCOS with another clinically significant abnormality (eg, metabolic syndrome or elevated lipids);
• Are unable or unwilling to maintain compliance with birth control measures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single treatment arm; ABSORICA® (isotretinoin) capsules 0.5 mg/kg/day for 4 weeks followed by 1.0 mg/kg/day for 16 weeks.	Drug: Isotretinoin; ABSORICA® (isotretinoin) capsules 0.5 mg/kg/day for 4 weeks followed by 1.0 mg/kg/day for 16 weeks; Other Names: ABSORICA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Active Treatment Period: Total Acne-Specific Quality of Life Score at Week 20	There are 4 domains: self-perception (22 questions), role-social (50 questions), role-emotional (33 questions), and acne symptoms (85 questions) in the acne-QOL questionnaires. Calculation of the domain scores was accomplished by summing all item responses within each domain. Self-perception: The range of possible scores is 0 to 30 points. Role-social: The range of possible scores is 0 to 24 points. Role emotional: The domain scores range from 0 to 30 points. Acne symptoms: The domain scores range from 0 to 30 points.	Week 20
Primary Efficacy Endpoint, Post-treatment Period: Subjects Requiring Retreatment During the Post-treatment Period and Time to Retreatment	subjects who were at least 75% compliant with their assigned treatment, had no major protocol violations, had a Week 20 count of total nodular lesions, and did not use any disallowed medications during the 20 weeks of treatment. (Retreated with Oral Isotretinoin Per Protocol Population).	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Active Treatment Period- Change From Baseline in Lesion Counts at Week 20	Change from baseline in the lesion count (nodules and inflammatory lesions) at the end of the ATP. (Per Protocol Population)	Baseline and at week 20
Active Treatment Period-Change From Baseline in Acne-Specific Quality of Life Total Score at Weeks 4, 8, 12, and 16	There are 4 domains: self-perception (22 questions), role-social (50 questions), role-emotional (33 questions), and acne symptoms (85 questions) in the acne-QOL questionnaires. Calculation of the domain scores was accomplished by summing all item responses within each domain. Self-perception: The range of possible scores is 0 to 30 points. Role-social: The range of possible scores is 0 to 24 points. Role emotional: The domain scores range from 0 to 30 points. Acne symptoms: The domain scores range from 0 to 30 points.	Baseline, at week 4, week 8, week 12, and week16
Active Treatment Period- Investigator's Global Assessment at Week 20	Investigator's Global Assessment score: 0 = Clear; = Almost Clear; = Mild; = Moderate; = Severe; = Very Severe	week 20
Active Treatment Period- Change From Baseline in Acne-Specific Quality of Life Domain Scores by Domain at Weeks 4, 8, 12, and 16	Acne-Specific Quality of Life, by domain: Self Perception: response on 0- to 6-point scale; the range of possible scores is 0 to 30 points. Role-social: response on 0- to 6-point scale; the range of possible scores is 0 to 24 points. Role-emotional: response on 0- to 6-point scale, exactly the same as those used for the Self Perception and Role-social domains. Acne Symptoms:response on 0- to 6-point scale, domain scores range from 0 to 30 points	20 weeks
Active Treatment Period- Change From Baseline in Nodule Count at Week 20		Baseline, and at week20
Post-treatment Period- Proportion of Subjects Requiring Treatment With Anti-Acne Medication and Time to Retreatment	Retreated with Prescription Anti-Acne Medication, n/Na (%); Over-the-Counter Anti-Acne Medication and Prescription or Over-the-Counter Anti-Acne Medication- Per Protocol Population.	104 weeks
Post-treatment Period- Severity of Acne by Lesion Count at Time of Retreatment With Oral Isotretinoin	change from Baseline	104 weeks
Post-treatment Period- Severity of Acne by Investigator's Global Assessment at Time of Retreatment With Oral Isotretinoin	Investigator's Global Assessment score: 0 = Clear; = Almost Clear; = Mild; = Moderate; = Severe; = Very Severe	104 weeks
Post-treatment Period- Severity of Acne by Lesion Count at Time of Retreatment With Prescription Other Than Oral Isotretinoin	Change from baseline	104 weeks
Post-treatment Period- Severity of Acne by Investigator's Global Assessment Score at Time of Retreatment With Over-the-Counter Medication	Investigator's Global Assessment score: 0 = Clear; = Almost Clear; = Mild; = Moderate; = Severe; = Very Severe	20 weeks
Post-treatment Period-Severity of Acne by Lesion Count at Each Visit During the Post-treatment Period		week 124
Post Treatment Period- Severity of Acne by Nodule Count at Each Visit During the Post-treatment Period	Change from Baseline-Week 124	week 124
Severity of Acne by Investigator's Global Assessment Score at Each Visit During the Post-treatment Period	Investigator's Global Assessment score: 0 = Clear; = Almost Clear; = Mild; = Moderate; = Severe; = Very Severe	week 124
Post-treatment Period- Severity of Acne by Lesion Count at Time of Retreatment With Over-the-Counter Medications	Change from Baseline	20 weeks
Post Treatment Period-Severity of Acne by Investigator's Global Assessment Score at Time of Retreatment With Prescription Other Than Oral Isotretinoin	Investigator's Global Assessment score: 0 = Clear; = Almost Clear; = Mild; = Moderate; = Severe; = Very Severe	20 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Treatment Period- Acne-Specific Quality of Life by Total Scores at the End of the Post-treatment Period	There are 4 domains: self-perception (22 questions), role-social (50 questions), role-emotional (33 questions), and acne symptoms (85 questions) in the acne-QOL questionnaires. Calculation of the domain scores was accomplished by summing all item responses within each domain. Self-perception: The range of possible scores is 0 to 30 points. Role-social: The range of possible scores is 0 to 24 points. Role emotional: The domain scores range from 0 to 30 points. Acne symptoms: The domain scores range from 0 to 30 points.	Visit 14/Week 124
Post-treatment Period- Acne-Specific Quality of Life by Domain Scores at the End of the Post-treatment Period	Acne-Specific Quality of Life, total and by domain: Self Perception: response on 0- to 6-point scale; the range of possible scores is 0 to 30 points. Role-social: response on 0- to 6-point scale; the range of possible scores is 0 to 24 points. Role-emotional: response on 0- to 6-point scale, exactly the same as those used for the Self Perception and Role-social domains. Acne Symptoms:response on 0- to 6-point scale, domain scores range from 0 to 30 points	Visit 14/Week 124

Collaborators and Investigators

• Sponsor: Sun Pharmaceutical Industries Limited
• Investigators: Study Director: Ashish Anvekar, MD, Ranbaxy Laboratories Limited

Publications and helpful links

General Publications

• Del Rosso JQ, Stein Gold L, Segal J, Zaenglein AL. An Open-label, Phase IV Study Evaluating Lidose-isotretinoin Administered without Food in Patients with Severe Recalcitrant Nodular Acne: Low Relapse Rates Observed Over the 104-week Post-treatment Period. J Clin Aesthet Dermatol. 2019 Nov;12(11):13-18. Epub 2019 Nov 1.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: May 16, 2015
• First Submitted That Met QC Criteria: May 28, 2015
• First Posted (Estimate): May 29, 2015

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Acne Vulgaris; Dermatologic Agents; Isotretinoin
• Other Study ID Numbers: ABS157LT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No