A Prospective, Multicenter, Randomized, Double-blind, Vehicle-controlled Phase 2 Study to Evaluate the Safety and Efficacy of a 
Combination Of 3% Minocycline and 0.3% Adapalene Topical Foam Formulation for the Treatment of Moderate-to-Severe Acne

James Q. Del Rosso, DO1; Linda Stein Gold, MD2; Zoe Draelos, MD3; Tooraj Joseph Raoof, MD4; Deirdre Hooper, MD5; Iain Stuart, PhD6
 1JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 2Henry Ford Health System, Detroit, MI; 3Dermatology Consulting Services, High Point, NC; 4T. Joseph Raoof, MD, Inc./Encino Research Center, Encino, CA; 5Audubon Dermatology, New Orleans, LA; 6VYNE Therapeutics Inc., Bridgewater, NJ

Introduction
• Acne vulgaris is a common disease of both males and females, usually manifesting initially 

during adolescence and affecting most of the population at some point during their lifetime1-3

• Acne is frequently treated with antibiotics, retinoids, or both1,4

 – Minocycline is a second-generation tetracycline with bacteriostatic and anti- 
inflammatory properties2,5

 – Adapalene is a third-generation retinoid that has anti-inflammatory and comedolytic 
properties, and normalizes keratinization1

• A fixed combination of minocycline 3% and adapalene 0.3%, FCD105, has been developed as  
a novel topical foam for the treatment of moderate-to-severe acne

 – Both of these molecules are used individually or in combination with other agents  
(eg, benzoyl peroxide) in FDA-approved treatments for acne although a retinoid/tetracycline 
topical formulation had not been evaluated in clinical studies prior to this study and may offer 
an improved treatment option for patients with moderate-to-severe acne

• The objectives of this study are:  

 – To evaluate the safety, tolerability, and efficacy of the combination product FCD105 in the 
treatment of moderate-to-severe acne vulgaris with up to 12 weeks of daily treatment, in 
comparison with vehicle

 – To compare the efficacy and safety of FCD105 against the individual, active-drug 
components: minocycline 3% and adapalene 0.3% topical foam products

Methods
• Study FX2016-40 was a randomized, multicenter, double-blind, vehicle-controlled, Phase 2 study

 – The purpose was to evaluate the safety, tolerability, and efficacy over a 12-week treatment 
period of FCD105 as compared with vehicle foam and the individual active components of 
FCD105 in the treatment of subjects with moderate-to-severe acne vulgaris in a 2x2 factorial 
design (Figure 1)

• Study drug administration

 – Subjects were randomized 5:3:4:4 to one of the following 4 color-matched foam treatments: 
FCD105 (minocycline 3% + adapalene 0.3%), vehicle, minocycline 3%, or adapalene 0.3%

 � Overall, there was high rate of study completion; 417 (93.3%) of the 447 subjects who 
were included in the ITT population completed the study, with comparable completion 
rates between treatment groups (Figure 1)

 – The assigned study treatment was applied once daily for 12 weeks

• Co-primary efficacy endpoints

 – Absolute change in inflammatory and noninflammatory lesion counts from baseline to  
week 12 for FCD105 vs. vehicle

 – Percent of subjects achieving IGA treatment success at week 12, where success was 
defined as a score of 0 (clear) or 1 (minimal) and a ≥2-grade improvement (decrease) from 
baseline for FCD105 vs. vehicle

• Secondary efficacy endpoints

 – Percentage change of inflammatory and noninflammatory lesion count for FCD105 vs 
vehicle at weeks 4, 8, and 12

 – Absolute change of inflammatory and noninflammatory lesion count for FCD105 vs 
minocycline 3% and FCD105 vs. adapalene 0.3% from baseline to week 12

 – Percent of patients achieving IGA treatment success at week 12 for FCD105 vs  
minocycline 3% and FCD105 vs. adapalene 0.3%

• Safety evaluations

 – Treatment-emergent adverse events, local skin tolerability assessments, vital signs, and 
physical examinations

• A subject satisfaction questionnaire was completed at baseline and week 12

Figure 1. Study design

Key Inclusion Criteria
•  ≥12 years of age

•  20–50 inflammatory lesions

•  25–100 noninflammatory
   lesions

•  IGA score of 3/4

•  ≤2 active face nodules

Baseline

FCD105 foam: ITT, n=142; Safety, n=142; Completed, n=130 (91.5%)

Vehicle foam; ITT, n=83; Safety, n=82; Completed, n=80 (96.4%)

Minocycline 3% foam: ITT, n=110; Safety, n=110; Completed, n=106 (96.4%)

Adapalene 0.3% foam: ITT, n=112; Safety, n=112; Completed, n=101 (90.2%)

Week 4 Week 8 Week 12
(end of treatment)

Week 16
(safety FU)

Subjects were randomized 5:3:4:4 to treatment with combination, vehicle, 
or an individual active component, respectively, from 35 U S  sites

IGA=Investigator’s Global Assessment, based upon a 5-point scale in which 0=clear, 1=minimal, 2=mild, 3=moderate, and 4=severe; FU, follow-up;  
ITT=intent-to-treat.

Results
Baseline Demographics and Disease Characteristics  
(ITT Population)
• Baseline demographics and disease characteristics were similar across treatment  

groups (Table 1)
• The majority of subjects were white (70.7%) and female (61.1%); mean age was 21.3 years

• The average inflammatory and noninflammatory lesion counts across groups at baseline were 
30.6 and 48.1, respectively; the majority of subjects (90.8%) had moderate (IGA=3) disease 
severity at baseline

Table 1. Baseline demographics and disease characteristics (ITT Population)

Variable
FCD105  
(n=142)

Vehicle  
(n=83)

Minocycline 
3%  

(n=110)

Adapalene 
0.3%  

(n=112)
Overall  
(N=447)

Age (years), mean (SD) 21.0 (7.05) 21.4 (7.25) 20.8 (8.28) 22.0 (7.98) 21.3 (7.63)

Age groups, n (%)

<18 years 64 (45.1) 32 (38.6) 55 (50.0) 41 (36.6) 192 (43.0)

18–40 years 76 (53.5) 50 (60.2) 52 (47.3) 70 (62.5) 248 (55.5)

41–64 years 2 (1.4) 1 (1.2) 3 (2.7) 1 (0.9) 7 (1.6)

Sex, n (%)

Male 62 (43.7) 33 (39.8) 43 (39.1) 36 (32.1) 174 (38.9)

Female 80 (56.3) 50 (60.2) 67 (60.9) 76 (67.9) 273 (61.1)

Ethnicity, n (%)

Hispanic or Latino 63 (44.4) 33 (39.8) 47 (42.7) 43 (38.4) 186 (41.6)

Not Hispanic or Latino 79 (55.6) 50 (60.2) 63 (57.3) 69 (61.6) 261 (58.4)

Race, n (%)

America Indian or Alaska 
Native 1 (0.7) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.2)

Asian 7 (4.9) 6 (7.2) 5 (4.5) 2 (1.8) 20 (4.5)

Black or African  
American 29 (20.4) 15 (18.1) 23 (20.9) 27 (24.1) 94 (21.0)

Native Hawaiian or 
Other Pacific Islander 0 (0.0) 1 (1.2) 0 (0.0) 0 (0.0) 1 (0.2)

White 103 (72.5) 56 (67.5) 81 (73.6) 76 (67.9) 316 (70.7)

Multiple 0 (0.0) 4 (4.8) 0 (0.0) 4 (3.6) 8 (1.8)

Not reported 2 (1.4) 1 (1.2) 1 (0.9) 3 (2.7) 7 (1.6)

Inflammatory lesion 
count, mean (SD) 30.2 (7.6) 30.0 (8.1) 31.0 (8.7) 31.1 (8.6) 30.6 (8.2)

Noninflammatory lesion 
count, mean (SD) 47.2 (16.7) 49.8 (16.5) 48.4 (19.1) 47.8 (16.9) 48.1 (17.3)

IGA score

Moderate (IGA=3) 134 (94.4) 76 (91.6) 96 (87.3) 100 (89.3) 406 (90.8)

Severe (IGA=4) 8 (5.6) 7 (8.4) 14 (12.7) 12 (10.7) 41 (9.2)

Efficacy Data
• FCD105 showed a statistically significant improvement compared with vehicle for the co-primary 

endpoints of IGA treatment success (Figure 2A) and absolute change in inflammatory lesions 
(Figure 2B) at week 12

 – By week 12, a significantly greater percent of subjects in the FCD105 group achieved IGA 
treatment success compared with the vehicle group

 – Daily application of FCD105 resulted in a significantly greater reduction in inflammatory 
lesions at week 12 compared with the vehicle group

• A numerical advantage of FCD105 vs. vehicle was observed in the absolute change in  
noninflammatory lesions at week 12 (Figure 2C)

Figure 2. Co-primary efficacy endpoints at week 12 (ITT population with MI)
IGA treatment success

35.9

15.7

0

5

10

15

20

25

30

35

40

45

50

FCD105 (n=142) Vehicle (n=83)

P
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IG

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t w
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12

a

P=0.0003b

A

FCD105 (n=142) Vehicle (n=83)

A
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c 

B Absolute reduction in 
inflammatory lesions

–24.9

-–30

–25

–20

–15

–10

–5

0

FCD105 (n=142) Vehicle (n=83)

A
bs

ol
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 w

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12
c

C Absolute reduction in 
noninflammatory lesions

P=0.321d

30.2e 30.0e 47.2e 49.8e

–19.4

–15.6

–22.9P=0.002d

–30

–25

–20

–15

–10

–5

0

MI=multiple imputation.
aIGA treatment success is defined as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline.
bCochran-Mantel-Haenszel test stratified by analysis center. P-value is for the null hypothesis that the risk ratio equals 1.
cPlotted data show the least squares means, which are defined as a model-based linear combination of the estimated effects.
dP-values are obtained from ANCOVA model with treatment as a main effect, baseline inflammatory lesion count as a covariate, and analysis center as a 
blocking factor.
eMean baseline lesion counts.

• A significantly greater percent of subjects in the FCD105 group achieved IGA treatment success 
than those in the vehicle group as early as week 8 (Figure 3A)

• The time course of the percent change in inflammatory lesions from baseline demonstrated 
a numerical advantage of FCD105 over vehicle as early as week 4; this difference became 
significant at week 12 (Figure 3B)

• For the percent change in noninflammatory lesions, a numerical advantage of FCD105 over 
vehicle was observed by week 8 and maintained at week 12 (Figure 3C)

Figure 3. Efficacy of FCD105 throughout the study duration (ITT population with MI)

P
er

ce
nt

 c
ha

ng
e 

in
 N

IL
s 

fr
om

 b
as

el
in

ec

–75

–50

–25

0
0 4 8 12

FCD105 (n=142)
Vehicle (n=83)

FCD105 (n=142)
Vehicle (n=83)

Week

–15.3

–34.3

–51.0

–17.3 –29.9

–45.9

P=0.6641d

P=0.3573d

P=0.2452d

IGA treatment successA B Percent change in ILs C Percent change in NILs

0.0
3.5

14.8

35.9

0.0
2.4

8.4

15.7

0
0 4

Week
8 12

5

10

15

20

25

30

35

40

45

50

S
ub

je
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s 
(%

) 
ac

hi
ev

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IG
A

 
tr

ea
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en
t s

uc
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ss
a

P=0.0491b

P=0.0003b

FCD105 (n=142)
Vehicle (n=83)

P
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ce
nt

 c
ha

ng
e 

in
 IL

s 
fr

om
 b

as
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in
ec

–75

–50

–25

0
0 4 8 12

P=0.1486d

P=0.4161d

P=0.0013d

FCD105 (n=142)
Vehicle (n=83)

Week

–32.9

–50.0

–64.1

–27.3

–46.7
–50.9

Ils-inflammatory lesions; NILs=non-inflammatory lesions.
aIGA treatment success is defined as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline.
bCochran-Mantel-Haenszel test stratified by analysis center. P-value is for the null hypothesis that the risk ratio equals 1.
cPlotted data show the least squares means, which are defined as a model-based linear combination of the estimated effects.
dP-values are obtained from ANCOVA model with treatment as a main effect, baseline inflammatory lesion count as a covariate, and analysis center as a 
blocking factor.

• FCD105 achieved all secondary efficacy endpoints by demonstrating a numerical advantage 
over both individual components in the percent of subjects achieving IGA treatment success 
(Figure 4A) and the absolute reduction in noninflammatory lesions (Figure 4C) at week 12, 
as well as demonstrating a lack of numerical inferiority to either component in the absolute 
reduction in inflammatory lesions at week 12 (Figure 4B)

 – FCD105 showed statistically significant improvements compared with adapalene 0.3% in all 
three endpoints at week 12

 – There was a significantly greater reduction in noninflammatory lesions at week 12 in the 
FCD105 group compared with the minocycline 3% group

Figure 4. Secondary efficacy endpoints at week 12 (ITT population with MI)

25.4

19.1
20.7

P=0.0033d

P=0.0292d

–19.7
–18.7

–15.8

30.2e 31.0e 31.1e

P=0.4053d

P=0.0012d

47.2e 48.4e 47.8e

0

5

10

15

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25

30

35

40

45

50

P
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–30

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12
c

C

FCD105 (n=142) Minocycline 3% (n=110) Adapalene 0.3% (n=112)

35.9

30.0

21.4

P=0.2569b
P=0.0114b

–30

–25

–20

–15

–10

-5

0

IGA treatment success Absolute reduction in 
inflammatory lesions

Absolute reduction in 
noninflammatory lesions

MI=multiple imputation.
aIGA treatment success is defined as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline.
bCochran-Mantel-Haenszel test stratified by analysis center. P-value is for the null hypothesis that the risk ratio equals 1.
cPlotted data show the least squares means, which are defined as a model-based linear combination of the estimated effects.
dP-values are obtained from ANCOVA model with treatment as a main effect, baseline inflammatory lesion count as a covariate, and analysis center as a 
blocking factor. 
eMean baseline lesion counts.

Safety Summary
• A summary of all AEs in the safety population is shown in Table 2

• There were no serious AEs reported during the course of the study

• Overall, most subjects reported AEs that were mild (10.3%) or moderate (4.0%) in severity

 – The incidence rate of severe AEs was similar across treatment groups

 – 2 subjects (0.4%) reported severe AEs

• A total of 4 subjects (0.9%) reported AEs that led to discontinuation of study drug

Table 2. Overall summary of adverse events (safety population)

FCD105  
(n=142)

Vehicle  
(n=82)

Minocycline 
3%  

(n=110)

Adapalene 
0.3%  

(n=112)
Overall  
(N=446)

Subjects with any AE, n (%) 21 (14.8) 10 (12.2) 15 (13.6) 20 (17.9) 66 (14.8)

Maximum severity, n (%)

Mild 12 (8.5) 7 (8.5) 13 (11.8) 14 (12.5) 46 (10.3)

Moderate 9 (6.3) 3 (3.7) 2 (1.8) 4 (3.6) 18 (4.0)

Severe 0 (0.0) 0 (0.0) 0 (0.0) 2 (1.8)a 2 (0.4)

Subjects with any treat-
ment-related AE, n (%) 5 (3.5)

b 0 (0.0) 2 (1.8)c 10 (8.9)d 17 (3.8)

Subjects with any SAE, 
n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Subjects with any AE  
leading to discontinuation, 
n (%)

1 (0.7)e 0 (0.0) 0 (0.0) 3 (2.7)f 4 (0.9)

Subjects with any AE  
leading to death, n (%)

0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

AE=adverse event; TEAE=treatment-emergent adverse event; SAE=serious adverse event
a2 cases of acne.
bDry skin, rash, dermatitis contact, pain of skin, burning sensation, and hyperesthesia.
cDry skin and nail discoloration.
d4 cases of dry skin, 2 cases each of rash, acne, and eye irritation, and 1 case each of skin discoloration, skin irritation, and erythema of eyelid.
eAcne.
f2 cases of acne and 1 case of rash.

• The incidence rate of the most frequently reported TEAEs (≥2% in any group) was similar 
between treatment groups (Table 3)

• Three subjects withdrew from the study due to a treatment-related TEAE, all in the adapalene 
0.3% group: acne, n=2 (1.8%); rash, n=1 (0.9%). There were no SAEs reported during the 
conduct of the study

Table 3. Summary of TEAEs occurring in >2% of subjects in any treatment 
group (safety population)

System Organ Class/ 
Preferred Term, n (%)a

FCD105  
(n=142)

Vehicle  
(n=82)

Minocycline 
3%  

(n=110)

Adapalene 
0.3%  

(n=112)
Overall  
(N=446)

Infections and infestations

Upper respiratory tract 
infection 2 (1.4) 4 (4.9) 3 (2.7) 1 (0.9) 10 (2.2)

Nasopharyngitis 2 (1.4) 0 (0.0) 3 (2.7) 0 (0.0) 5 (1.1)

Viral upper respiratory 
tract infection 0 (0.0) 2 (2.4) 0 (0.0) 1 (0.9) 3 (0.7)

Skin and subcutaneous 
tissue disorders

Dry skin 2 (1.4) 0 (0.0) 1 (0.9) 4 (3.6) 7 (1.6)

Nervous system disorders

Headache 1 (0.7) 3 (3.7) 2 (1.8) 2 (1.8) 8 (1.8)

aSummary of TEAEs occurring in >2% of subjects in any treatment group, listed in descending order based on the overall total within each system  
organ class.

• Local facial tolerability assessments at week 12 demonstrated that FCD105 was well  
tolerated (Figure 5)

• The majority of subjects (≥89.9%) across all treatment groups recorded local tolerability 
assessments as “none” or “mild” at week 12; no notable differences were observed between 
treatment groups

• At least 93% of subjects treated with FCD105 rated local facial tolerability as “none” or “mild” for 
all 6 measures of local facial tolerability

Figure 5. Local facial tolerability assessments at week 12 (safety population, 
observed cases)

0
BL Wk

4
Wk
8

Wk
12

BL Wk
4

Wk
8

Wk
12

BL Wk
4

Wk
8

Wk
12

BL Wk
4

Wk
8

Wk
12

BL Wk
4

Wk
8

Wk
12

BL Wk
4

Wk
8

Wk
12

0.25

0.5

0.75

1

M
ea

n 
S

ev
er

ity
 S

co
re

 (
ra

ng
e 

of
 0

=n
on

e 
to

 3
=s

ev
er

e)
a

Itching HyperpigmentationErythemaScalingDrynessBurning
and stinging

FCD105 Vehicle Minocycline 3% Adapalene 0.3%

BL=baseline; Wk4=Week 4; Wk8=Week8; Wk12=Week 12.
aLocal signs and symptoms were assessed on a 4-point scale including 0=none, 1=mild, 2=moderate, and 3=severe.

Summary
Limitations
• A limitation of the study relates to the generalizability of the data to a larger population or to 

patients less than 12 years of age

• Future studies are needed to confirm these findings and evaluate the safety profile of FCD105 
over longer treatment durations

Conclusions
• Statistically significant improvement in disease burden was observed for FCD105 foam vs 

vehicle foam for the absolute change in inflammatory lesion count and IGA treatment success  
at week 12

• Numerical superiority was demonstrated for FCD105 over vehicle foam for the absolute change 
in noninflammatory lesions at week 12

• Numerical advantage of FCD105 foam over both minocycline 3% foam and adapalene 0.3% foam 
was observed at week 12, with the majority of comparisons being statistically significant

• TEAEs were few in type and frequency. Most were mild in severity, no serious TEAEs were 
reported, and subject discontinuations due to TEAEs were low

• FCD105 demonstrated a favorable tolerability profile, with most (≥93%) local signs and 
symptoms in this group being reported as “none” or “mild” at week 12

• These data are supportive to continue the development of FCD105 into Phase 3 clinical 
evaluation for the treatment of moderate-to-severe acne vulgaris 

Funding
This study was funded by Foamix Pharmaceuticals Ltd, a wholly owned subsidiary of VYNE Therapeutics Inc.

Disclosures/Acknowledgments
Disclosures 
Dr. Del Rosso is a consultant for Aclaris, Almirall, Athenex, Cutanea, Dermira, Ferndale, Galderma, Genentech, LEO Pharma, 
Menlo, Novan, Ortho, Pfizer, Promius, Sanofi/Regeneron, SkinFix, and SunPharma; he has received research support from 
Aclaris, Almirall, Athenex, Botanix, Celgene, Cutanea, Dermira, Galderma, Genentech, LEO Pharma, Menlo, Novan, Ortho, 
Promius, Regeneron, SunPharma, and Thync; he receives honoraria from Aclaris, Celgene, Galderma, Genentech, LEO 
Pharma, Novartis, Ortho, Pfizer, Promius, Sanofi/Regeneron, and SunPharma; and he participates in speakers bureaus for 
honoraria from Aclaris, Celgene, Galderma, Genentech, LEO Pharma, Novartis, Ortho, Pfizer, Promius, Sanofi/Regeneron, 
and SunPharm. Dr. Stein Gold is an advisor and investigator for Foamix Pharmaceuticals Inc, Galderma, LEO Pharma, 
Novartis, and Valeant and is an investigator for Janssen, AbbVie, and Solgel. Dr. Draelos is a principal investigator and 
advisor for Foamix Pharmaceuticals Inc. Dr. Raoof is an investigator for Foamix Pharmaceuticals Inc. Dr. Hooper has served 
as an investigator for Foamix Pharmaceuticals; she reports honoraria from Allergan, Almirall Aesthetics, Aqua Galderma 
USA, Cutera, Inc., Ferndale, La Roche Posay, Pixacore, RBC Consultants (clarisonic), Revance, and Viviscal; she reports 
other financial benefits from Actavis, Dermira, GSK, Mylan, and Sol Gel. Dr. Stuart is an employee and stockholder at VYNE 
Therapeutics Inc.

Acknowledgments
Editorial support was provided by Scient Healthcare Communications.

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