[POST HOC ANALySIS]

The Efficacy and Tolerability of a Fixed

Combination Clindamycin (1.2%) and Benzoyl
Peroxide (3.75%) Aqueous Gel in Adult
Female Patients with Facial Acne Vulgaris
JOSHUA A. ZEICHNER, MD
Mount Sinai Hospital, New York, New York

ABSTRACT
Objective: To investigate the efficacy and tolerability of clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel or
vehicle monotherapy in adult female acne patients. Methods: A post hoc analysis in 72 adult female patients (aged 25
years) with moderate-to-severe acne receiving clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel or vehicle for 12
weeks. Results: The efficacy of clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel was significantly greater than
vehicle. The mean percent change from baseline in inflammatory and noninflammatory lesion counts and the percentage
of patients who achieved a 2-grade reduction in the Evaluators Global Severity Score was 68.7%, 60.4, and 52.7 percent,
respectively (P=0.019, 0.020 and 0.074 versus vehicle). In addition, 44 percent of patients reported their acne to be clear
or almost clear at Week 12 (P=0.026 versus vehicle). No substantive differences were seen in cutaneous tolerability
among treatment groups, and no patients discontinued treatment because of adverse events. Limitations: It is not
possible to determine the contributions of the individual active ingredients, and this study was not set up specifically to
investigate the treatment of adult female acne. Conclusion: Clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel
provides statistically significant greater efficacy than vehicle in treating acne in adult female patients and has a favorable
safety and tolerability profile. (J Clin Aesthet Dermatol. 2015;8(4):2125.)

A
cne vulgaris is a very common skin disease that
usually presents in adolescence, but frequently
continues into adulthood. An increasing number of
older women are seeking acne treatment from
dermatologists.1,2 A recent study of almost 3,000 women
taken from a general population showed that although
acne peaked in teenage years, 45 percent of women aged
21 to 30, 26 percent aged 31 to 40, and 12 percent aged 41
to 50 suffered from acne.3
The pathogenesis of adult acne and its differences from
that of teenage acne are unclear. In general, adult women
with acne have high levels of sebum. Smoking has also
been identified as an aggravating factor for patients with
pre-existing acne or with a genetic predisposition.4,5 The
majority of patients have a first-degree family history of
postadolescent acne,6 a factor known to increase the risk
of adult acne by four percent.7 Acne has been shown to be
associated with psychiatric comorbidities in adult women.
One study reported 40 percent of adult female acne
patients suffer from depression,8 and daily stress has been
shown to exacerbate the condition.9
Postadolescent acne is broadly categorized into two
main groupspersistent (the most common) and late-
onset acne. Patients with persistent acne are those who
developed acne in adolescence and the acne did not
resolve.10 Late-onset acne, on the other hand, refers to
patients who were clear in their teenage years, but
developed acne later in life. Traditionally, adult acne has
been described as an inflammatory condition affecting
predominantly the lower one-third of the face and jawline.
Frequently, patients report a premenstrual flare occurring
1 to 2 weeks prior to menses. However, recent data now
challenge this notion. In a recent international study
evaluating 374 women, investigators found that in 90
percent of patients, facial acne distribution was similar to
that of teenagers. Moreover, acne was characterized not

DISCLOSURE: Dr. Zeichner is a consultant to Valeant.

ADDRESS CORRESPONDENCE TO: Joshua A. Zeichner; E-mail: joshzeichner@gmail.com

[April 2015 Volume 8 Number 4] 21

 TABLE 1. Baseline characteristics and patient disposition (intent-to-treat population, females where age 25 years)
CLIN/BP GEL
(N=29)
Inflammatory lesion count 25.2
(mean/SD) (4.70)
Noninflammatory lesion count 37.1
(mean/SD) (17.06)
23
Moderate acne (EGSS=3), N/%
(79.3%)
6 11
Severe acne (EGSS=4), N/%
(20.7%)
only by inflammatory lesions, but also comedones.11 A
cross-sectional, web-based survey of 208 adult women
revealed similar data, noting facial acne on the cheeks,
chin, and forehead. This study also assessed disease
burden, with three of four respondents reporting that
their acne was moderately, severely, or very severely
troublesome.12
Data on the treatment of acne in the adult female
population is limited. Recently, efficacy and tolerability
data on a new fixed combination product, clindamycin
phosphate 1.2%/benzoyl peroxide (BP) 3.75% gel was
reported.13 A post hoc analysis was performed to evaluate
efficacy and cutaneous tolerability of this product in adult
female patients enrolled in the study.
METHODS
Detailed methodology has already been reported
elsewhere; however, a summary is provided below.13
Study design. A total of 498 patients with moderate-
to-severe acne vulgaris were randomized (1:1) to receive
clindamycin phosphate 1.2%/BP 3.75% gel, or vehicle in a
multicenter, double-blind, controlled, 12-week study.
Patients were stratified by severity of acne (Evaluators
Global Severity Score [EGSS], ranging from 0 [clear] to 5
[very severe]). They were dichotomized into a moderate
(EGSS of 3) and a severe acne group (EGSS of 4).
The post hoc analysis compared data between
clindamycin phosphate 1.2%/BP 3.75% gel and vehicle in
female patients aged 25 years old.
Study population. Patients were included of any race
or ethnicity with moderate-to-severe acne, defined as 20
to 40 inflammatory lesions (papules, pustules, and
nodules), 20 to 100 noninflammatory lesions (open and
closed comedones), and no more than two nodules.
22 [April 2015 Volume 8 Number 4]
VEHICLE TOTAL
(N=43) (N=72)
25.4 25.3
(5.37) (5.08)
33.3 34.8
(14.82) (15.75)
32 55
(74.4%) (76.4%)
17
(25.6%) (23.6%)
Standard washout periods were required for patients
using previous prescription and over-the-counter acne
treatments.
Efficacy evaluation. Efficacy evaluations included
inflammatory and noninflammatory lesion counts and
EGSS at screening, baseline, and during treatment (Weeks
4, 8, and 12). Primary efficacy endpoints included
absolute change in mean inflammatory and
noninflammatory lesion counts, and the proportion of
patients who achieved at least a 2-grade reduction in
EGSS from baseline to Week 12. Secondary efficacy
endpoints included mean percent change from baseline to
Week 12 in inflammatory and noninflammatory lesion
counts and the proportion of patients who considered
themselves clear or almost clear at Week 12 (Subject
Self-Assessment [SSA]).
Safety evaluation. Cutaneous safety (erythema and
scaling) and tolerability (itching, burning, and stinging)
were evaluated at each study visit on a scale of 0 (none)
to 3 (severe). Adverse events (AEs) were evaluated
throughout the study.
Statistical analysis. The intent-to-treat (ITT)
population comprised all patients randomized and
provided with study drug. The safety population
comprised all randomized patients who were presumed to
have used the study medication at least once and who
provided at least one post baseline evaluation.
The investigator assessments (EGSS, lesion counts)
were conducted independently of the SSA. Statistical
significance was based on 2-tailed tests of the null
hypothesis resulting in P-values of 0.05 or less.
All AEs occurring during the study were recorded and
classified on the basis of medical dictionary for drug
regulatory activities terminology for the safety population.
22
The Fisher exact test was used to
compare the proportion of patients in
each treatment group who reported
any AE at a significance level of 0.05.

RESULTS
Baseline characteristics. Overall,
72 female patients aged 25 years
were treated with clindamycin
phosphate 1.2%/BP 3.75% gel (N=29)
or vehicle (N=43) for 12 weeks.
Total lesion counts at baseline were
62.3 and 58.9 (active treatment and
vehicle, respectively), with no
significant difference between the two
treatment groups. The majority of
patients (N=55, 76.4%) had moderate
acne. There were proportionately Figure 1. Mean percent reduction in lesion counts: Female patients aged 25 years
more severe acne patients (23.6%) in (ITT population) at Week 12
the adult female subgroup than in the
total study population (17.3%). See
Table 1 for baseline characteristics
and patient disposition by treatment
group.
Efficacy. In female patients aged
25 years, efficacy results with
clindamycin phosphate 1.2%/BP
3.75% gel were greater than vehicle
for each of the primary and secondary
endpoints, achieving statistical
significance in mean lesion count
reduction, mean percent lesion
reduction, and SSA. Treatment
success was numerically, but not
statistically, greater in the active arm
compared to vehicle.13
Lesion counts. The reduction in
Figure 2. Treatment success: Female patients aged 25 years (ITT population)
inflammatory and noninflammatory
at Week 12
lesion counts was significantly greater
with clindamycin phosphate 1.2%/BP
3.75% gel compared with vehicle. The
absolute mean reduction in
inflammatory and noninflammatory
lesion counts with clindamycin
phosphate 1.2%/BP 3.7% gel were
17.0 and 22.0 respectively compared
to 9.6 and 10.1 with vehicle.
Mean percent change from baseline
to Week 12 in inflammatory and
noninflammatory lesion counts with
clindamycin phosphate 1.2%/BP 3.7%
gel was 68.7 and 60.4 percent,
respectively, compared to 39.7 and
34.0 percent with vehicle (P=0.019
and 0.020, respectively, Figure 1).
Evaluators Global Severity Score
(EGSS). Overall treatment success Figure 3. Patients reporting clear, almost clear, or marked improvement in their acne:
(2 grade reduction in EGSS from Female patients aged 25 years (ITT population) Weeks 212

[April 2015 Volume 8 Number 4] 23

baseline) with clindamycin phosphate 1.2%/BP 3.75% gel
was achieved in 52.7 percent of adult female patients,
compared to 30.0 percent with vehicle. This was
numerically greater than, but not statistically different
from, vehicle (P=0.074, Figure 2).
Subject Self-Assessment (SSA). At baseline,
approximately 80 percent of female patients reported
their acne covered at least 50 percent of their face. By
Week 12, 44.0 percent of patients reported their acne to
be clear or almost clear (<10%) using clindamycin reduction, and more than 50 percent of patients achieved
1.2%/BP 3.75% gel compared to only 13.5 percent using
vehicle (P=0.026). More than 70 percent of patients
reported at least a marked (75%) improvement in their
acne at Week 12 with active drug, twice that seen with
vehicle over the same time period (Figure 3).
Safety. Overall, six (22.2%) patients treated with
clindamycin 1.2%/BP 3.75% gel and seven (16.7%)
patients treated with vehicle reported at least one AE.
None were serious, and all were mild or moderate in
severity. One reported AE in each treatment arm was
related to study medication (burning sensation, contact
dermatitis). Neither led to discontinuation from the study.
Cutaneous Tolerability Assessment. Overall mean
scores for cutaneous safety (erythema and scaling) and
tolerability (itching, burning, and stinging) at baseline and
at each post-baseline visit were <1 (where 1=mild). There
were no statistical differences between the clindamycin
phosphate 1.2%/BP 3.75% gel and vehicle groups (data
not shown). Almost 80 percent of patients reported no
cutaneous tolerability issues at all throughout the study.
There was only one report of moderate scaling and
burning (a score of 2), and two reports of moderate
itching over the 12-week treatment period with
clindamycin phosphate 1.2%/BP 3.75% gel. The case of
moderate scaling was reported at Week 4 and then
improved. Moderate burning and itching were reported at
the end of the study (Week 12).
No patient in the clindamycin phosphate 1.2%/BP
3.75% gel group experienced severe local signs or
symptoms or discontinued study treatment because of
AEs.
DISCUSSION
Post-adolescent acne remains a challenge to treat.
There is little data explaining why acne begins or persists
in adulthood, why adult women are affected significantly
more than men, and what etiological and aggravating
factors are the most important. Acne in adult women has
a significant impact on quality of life, is associated with
depressive symptoms and anxiety, and negatively
influences performance in the workplace.12 Specific
characteristics of acne in adult women must be considered
when selecting a treatment regimen.14 These include
issues related to the skin and hormonal status of the
patient as well as lifestyle issues and patient preferences.
Finally, a simple regimen tailored to the patients needs
encourages adherence to the regimen and will ultimately
improve outcomes.15
24 [April 2015 Volume 8 Number 4]
Clindamycin phosphate 1.2%/BP 3.75% gel is a safe and
effective treatment for a variety of acne patients and
demonstrated patient satisfaction, with a reduction in the
perception of facial skin oiliness.13 In this post hoc
analysis, adult women at least 25 years old with moderate-
to-severe acne were evaluated. Similar to data seen in the
overall population of the pivotal study, in this study
clindamycin phosphate 1.2%/BP 3.75% gel was
statistically more effective than vehicle in lesion count
treatment success at Week 12. Almost 20 percent of
patients reported a marked improvement in their acne as
early as Week 2. More than 80 percent of the adult female
patients had acne covering at least 80 percent of their face
at the start of the study, and more than 70 percent
reported at least a marked improvement in their acne by
Week 12.
While an effective drug is important in an acne
treatment, tolerability is as important as it drives
treatment adherence. Especially in the adult woman, who
is cosmetically camouflaging acne with makeup,
medication tolerability and lack of skin irritation is
paramount. Clindamycin phosphate 1.2%/BP 3.75% gel
was well-tolerated in this patient population, with overall
mean scores for erythema, scaling, itching, burning, and
stinging reported as mild or none throughout the study.
Moreover, there were no statistical differences in
tolerability between patients in the active and vehicle
groups.
There are limitations to this study. It is not possible to
assess the contributions from the individual active
ingredients, although previous studies with
clindamycin/BP fixed combinations have demonstrated a
synergistic effect.16 Also, these are data derived from the
controlled setting of a clinical trial, which does not
translate directly to the real-world clinical setting.
Moreover, the pivotal study from which this analysis was
performed was not set up specifically to study adult
female acne patients, and as such the patient population in
this post hoc analysis may not be representative of the
typical female acne patient that presents in our practice.
Future studies should be performed in adult women with
acne to confirm these data.
ACKNOWLEDGMENT
The author acknowledges Brian Bulley, MSc, of Inergy
Limited for medical writing support. Valeant
Pharmaceuticals North America LLC funded Inergys
activities pertaining to this manuscript.
REFERENCES
1. Preneau S, Dreno B. Female acnea different subtype of
teenager acne? J Eur Acad Dermatol Venereol.
2012;26(3):277282.
2. Knaggs HE, Wood EJ, Rizer RL, et al. Post-adolescent acne.
Int J Cosmet Sci. 2004;26(3):129138.
3. Perkins AC, Maglione J, Hillebrand GG, et al. Acne vulgaris in
women: prevalence across the life span. J Womens Health.
24
 2012;21(2):223230.
4. Capitanio B, Sinagra JL, Ottaviani M, et al. Smokers acne: a
new clinical entity? Br J Dermatol. 2007;157:10701071.
5. Schfer T, Nienhaus A, Vieluf D, et al. Epidemiology of acne
in the general population: the risk of smoking. Br J Dermatol.
2001;145:100104.
6. Goulden V, Clark SM, Cunliffe WJ. Post-adolescent acne: a
review of clinical features. Br J Dermatol. 1997;136:6670.
7. Goulden V, McGeown CH, Cunliffe WJ. The familial risk of
adult acne: a comparison between first-degree relatives of
affected and unaffected individuals. Br J Dermatol.
1999;141:297300.
8. Henkel V, Moehrenschlager M, Hegerl U, et al. Screening for
depression in adult acne vulgaris patients: Tools for the
dermatologist. J Cosmet Dermatol. 2002;1:202207.
9. Albuquerque RG, Rocha MA, Bagatin E, et al. Could adult
female acne be associated with modern life? Arch Dermatol
Res. 2014;306(8):683688.
10. Geller L, Rosen J, Fraknkel A, et al. Perimenstrual flare of
adult acne. J Clin Aesthet Dermatol. 2014;7(8):3034.
11. Dreno B, Thiboutot D, Layton AM, et al. Large-scale
[April 2015 Volume 8 Number 4]
international study enhances understanding of an emerging
acne population): adult females. J Eur Acad Dermatol
Verereol. 2014 Oct 8. [Epub ahead of print].
12. Tanghetti EA, Kawata AK, Daniels SR, et al. Understanding
the burden of adult female acne. J Clin Aesthet Dermatol.
2014;7(2):2230.
13. Pariser DM, Rich P, Cook-Bolden FE, Korotzer A. An aqueous
gel fixed combination of clindamycin phosphate 1.2% and
benzoyl peroxide 3.75% for the once- daily treatment of
moderate to severe acne vulgaris. J Drugs Dermatol.
2014;13(9):611617.
14. Holzmann R, Shakery K. Postadolescent acne in females.
Skin Pharmacol Physiol. 2014;27(Suppl 1):38.
15. Dreno B, Layton A, Zouboulia CC, et al. Adult female acne: a
new paradigm. J Eur Acad Dermatol Venereol. 2013;27(9):
10631070.
16. Thiboutot D, Zaenglein A, Weiss J et al. An aqueous gel fixed
combination of clindamycin phosphate 1.2% and benzoyl
peroxide 2.5% for the once-daily treatment of moderate to
severe acne vulgaris: assessment of efficacy and safety in
2813 patients. J Am Acad Dermatol. 2008;59:792800.
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