Presented at the 13th Winter Clinical Dermatology Conference, January 12 –17, 2018, Maui, HI, USA

An Open-label Study Evaluating the Long-term Efficacy, Quality of Life, and Safety of 
Lidose-Isotretinoin (ABSORICA®) Capsules Administered Without Food in Patients With 
Severe Recalcitrant Nodular Acne: Interim Analysis of 20-Week Active Treatment Period 
Andrea Zaenglein,1 James Del Rosso2
1Department of Dermatology, Pennsylvania State University, Hershey, PA, USA; 2JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV, USA

BACKGROUND
• Severe acne is known to have a significant adverse 

effect on self-esteem and quality of life (QOL).1 
Effective treatment of acne, with isotretinoin, can 
subsequently improve the patient’s QOL. The timing 
of QOL improvement over the course of treatment with 
lidose-isotretinoin has not been established

• Isotretinoin products must be taken with a high-fat 
meal to achieve optimal absorption. Fasted plasma 
levels of isotretinoin can be nearly 60% lower than 
fed levels.2 Noncompliance with the food intake 
requirements can potentially compromise the  
long-term efficacy of isotretinoin3

• Absorption of lidose-isotretinoin is less dependent on 
the amount and/or type of food intake and it can be 
taken without meals, while still providing a reliable 
isotretinoin blood concentration4

OBJECTIVE
• To evaluate the efficacy and safety of lidose-isotretinoin 

taken without food by patients with severe recalcitrant 
nodular acne, in addition to assessing their quality of life

 – Primary objective during the 20-week active treatment 
period (ATP) was to evaluate the QOL of patients 
taking lidose-isotretinoin twice daily (bid) without food

 – Secondary objectives during the ATP were to 
evaluate the efficacy and safety of lidose-isotretinoin 
taken bid without food

METHODS
Study Design
• This is a phase 4, multicenter, single-arm, open-label 

study conducted in the United States in patients  
with severe recalcitrant nodular acne (NCT02457520, 
Figure 1) consisting of 2 phases: a 20-week (5-month) 
open-label ATP and a 104-week (2-year)  
post-treatment period

Study Population
• Key inclusion criteria included:

 – 12–45 years of age
 – Recalcitrant acne severe enough for isotretinoin 
treatment, including ≥5 facial nodules

 – No prior exposure to systemic isotretinoin or other 
systemic retinoid

 – Weight 40–110 kg
 – Women must not be pregnant and must not be 
breastfeeding; female patients of childbearing 
potential must use 2 forms of effective 
contraception simultaneously for 1 month before 
trial, during trial, and for 1 month after stopping 
study medication or commit to continuous 
abstinence from heterosexual intercourse, and 
have a negative serum pregnancy test

Treatment
• Dosing during 20-week ATP to attain target cumulative 

dose of 120–150 mg/kg:
 – 0.5 mg/kg/day divided into 2 daily doses for 4 weeks 
followed by

 – 1.0 mg/kg/day divided into 2 daily doses for 16 weeks
• Study medication was taken without food (1 hour 

before or at least 2 hours after ingestion of  
food/beverages other than water)

Endpoints
• Primary efficacy endpoint was the change from 

baseline to the end of treatment (EOT) in the  
Acne-QOL score, assessed on a graded scale  
(overall and by domain)

 – Domains included self-perception, role-social,  
role-emotional, and acne symptoms

• Secondary efficacy endpoints included monthly 
change from baseline in Acne-QOL scores (overall 
and by domain) and lesion counts during the ATP and 
change from baseline to EOT in Investigator’s Global 
Assessment (IGA) scores

Statistical Analysis
• Efficacy evaluation was conducted using the  

intent-to-treat population
• Overall Acne-QOL score, each domain score, and 

the changes from baseline for these scores were 
summarized using descriptive statistics. Differences 
between baseline and postbaseline values were 
analyzed using paired t-tests

• Descriptive statistics are provided for mean percentage 
change from baseline value for inflammatory, 
noninflammatory, and total lesion counts. Differences 
between baseline and postbaseline values were 
analyzed using paired t-tests

• Descriptive statistics are provided for IGA  
observed values

Table 1. Baseline Demographics

All Patients Enrolled 
(N=201)

Gender, n (%)
Male 125 (62.2)
Female 76 (37.8)

Race, n (%)
American Indian or Alaska native 3 (1.5)
Asian 8 (4.0)
Black or African American 17 (8.5)
Multiple 1 (0.5)
Native Hawaiian or other Pacific islander 1 (0.5)
Other 4 (2.0)
White 167 (83.1)

Ethnicity, n (%)
Hispanic or Latino 31 (15.4)

Age, y
Mean (SD) 18.7 (6.4) 
Range 12–45

Table 2. Baseline Disease Characteristics

Intent-to-Treat  
Population

(N=197)
Number of inflammatory lesions

Mean (SD) 33.8 (17.0)
Median (range) 32 (5–108)

Number of noninflammatory lesions
Mean (SD) 40.1 (41.3)
Median (range) 27 (0–250)

Investigator’s Global Assessment score
Mean (SD) 4.1 (0.5)
Median (range) 4 (3–5)

REFERENCES
1. Ritvo E, et al. Biopsychosoc Med. 2011;5:11–24.
2. Colburn WA, et al. J Clin Pharmacol. 1983;23:534–539.
3. Del Rosso JQ. J Clin Aesthet Dermatol. 2012;5:17–24.
4. Webster GF, et al. J Am Acad Dermatol. 2013;69:762–767.

ACKNOWLEDGMENTS
Editorial support for this poster was provided by Anna Houlihan of Sun Pharmaceutical 
Industries, Inc., and Fishawack Communications, funded by Sun Pharmaceutical 
Industries, Inc. Statistical support for this poster was provided by Novella Clinical, funded 
by Sun Pharmaceutical Industries, Inc.
Lidose-isotretinoin is a retinoid indicated for the treatment of severe recalcitrant 
nodular acne in patients 12 years of age and older. AZ and JD consulted on the design 
and implementation of this clinical trial for Sun Pharmaceutical Industries, Inc., who 
sponsored the study and supported the development of this presentation. 

DISCLOSURES
AZ has served as a consultant for Cassiopea and Ranbaxy/Sun Pharmaceutical 
Industries, Inc. JD has served as a consultant, speaker, and research investigator for Sun 
Pharmaceutical Industries, Inc.

Figure 1. Study Design

Screening

Within
≤30 days of

baseline

Visit:

Weeks:

Baseline EOT EOS

2 3 4 5 6 7 8 9 10 11 12 13 141

0 2 4 8 12 16 20 24 32 46 72 98 124

Screening period 
(0–45 days)

Active treatment period 
(20 weeks)

Post-treatment period 
(104 weeks)

EOS=end of study; EOT=end of treatment. 

Figure 2. Patient Disposition

N=201
Enrolled

n=170
Completed ATP

n=3
Status unknown

n=8
LTFU

n=8
Discontinued
owing to AE

n=1
Protocol deviation 

n=1
Physician decision 

n=1
Other

n=6
Withdrawal
by subject

n=3
Noncompliance
with study drug

N=197
ITT population

(n=4 did not receive
study medication)

AE=adverse event; ATP=active treatment period; ITT=intent-to-treat; LTFU=lost to follow-up.

Figure 3. Improvement in Acne-QOL Scores at Week 4 
and EOT

40

30

20

10

0

A
cn

e-
Q

O
L 

S
co

re
, M

ea
n 

(S
D

)

Self-
perception

Role-
Social

Role-
Emotional

Acne
Symptoms

15.8

20.1

26.0

**

**

15.4
18.0

21.6

**
**

15.6

20.1

25.6

**

**

14.6

19.8

25.8
**

**

120

100

80

60

40

20

0
Overall

61.4

77.9

99.0

**

**

Baseline (n=197) Week 4 (n=166) EOT (n=197)

EOT values reflect the last visit for which a subject had data in the ATP. **P≤0.0001.
ATP=active treatment period; EOT=end of treatment; QOL=quality of life.

Figure 5. IGA Scores Over Time From Baseline to EOT 
5

4

3

2

1

0

IG
A

 S
co

re
, M

ea
n 

(S
D

)

Baseline 4 8 12
Weeks

16 20 EOT

4.1

3.5

3.1

2.4

1.9

1.1 1.2

EOT values reflect the last visit for which a subject had data in the ATP. 
ATP=active treatment period; EOT=end of treatment; IGA=Investigator’s Global Assessment.

Figure 4. Mean Change in Lesion Counts From 
Baseline to EOT

**

0

−20

−40

−60

−80

−100

C
ha

ng
e 

F
ro

m
 B

as
el

in
e,

 M
ea

n,
 %

4 8 12
Weeks

16 20 EOT

**

**
**

** ** ********
**

**

**

**

*

**

**
**

−83.2
−85.3
−87.2

Inflammatory Lesions

Total
Noninflammatory Lesions

EOT values reflect the last visit for which a subject had data in the ATP. Differences between 
postbaseline and baseline values analyzed using paired t-tests. *P=0.0002; **P≤0.0001. 
ATP=active treatment period; EOT=end of treatment.

CONCLUSIONS
• Twice-daily use of lidose-containing isotretinoin taken 

without food improved patients’ QOL over the 20-week 
treatment period, with improvement seen as early as 
Week 4

• Clinical efficacy was also demonstrated
• AEs were generally consistent with the known safety 

profile for isotretinoin

RESULTS
Disposition
• A total of 201 patients (mean age: 18.7 [range: 12–45] 

years) were enrolled in the study at 21 sites (Figure 2)
 – 85% (170/201) of patients completed the  
20-week ATP

Efficacy
• There was a significant increase in mean (SD) 

Acne-QOL from baseline to EOT (61.4 [28.4] vs 99.0 
[19.8], P<0.0001). All 4 domains (self-perception, 
role-social, role-emotional, acne symptoms) were 
significantly improved over the course of treatment, with 
positive improvements beginning at Week 4 (Figure 3)

• Mean (SD) percentage change in inflammatory 
(‒87.2 [22.5]) and noninflammatory lesion (‒83.2 [30.3]) 
counts from baseline to EOT were significant 
(P<0.0001) (Figure 4)

• Mean IGA scores improved from baseline by 
approximately 3.0 points at EOT (Figure 5)

Safety
• A total of 286 adverse events (AEs) was reported in 

60.2% of patients (121/201)
 – The most common AEs were dry skin (10.9%), dry 
lips (10.4%), and cheilitis (9.0%)

• A total of 166 treatment-related AEs was reported in 
46.3% of patients (93/201)

 – The most commonly reported were dry lips 
(10.4%), dry skin (10.4%), and cheilitis (9.0%)

• Twelve severe AEs were reported; 5 were considered 
to be treatment related  

 – Nausea (n=2), increased blood cholesterol (n=1), 
liver function test abnormal (n=1), and headache (n=1)

• Psychiatric AEs occurred in 17 patients (8.5%). The 
psychiatric events reported in more than 1 patient were 
depression (4.0%), insomnia (1.0%), and anxiety (1.0%)

• Abnormal laboratory results occurred in 11 patients 
(5.5%); those reported in more than 1 patient were 
blood triglycerides increased (3.5%), increased 
alanine aminotransferase (1.5%), increased aspartate 
aminotransferase (1.5%), and blood cholesterol 
increased (1.5%)

• One serious AE was reported: diabetes mellitus on 
study Day 127, severe in intensity and unlikely related 
to study treatment

• Eight patients discontinued the study owing to AE
 – Psychiatric events (n=5) and abnormalities in 
laboratory test results (n=3)

 – Six additional patients had study drug withdrawn 
for an AE: psychiatric events (n=4), migraine (n=1), 
and diabetes mellitus (n=1)

• Baseline demographics and disease characteristics 
are presented in Tables 1 and 2