Open-Label Extension Study Evaluating the Long-Term Safety, Efficacy, and Tolerability of  
FMX103 1.5% Topical Minocycline Foam in the Treatment of Moderate-to-Severe Facial Papulopustular Rosacea

Linda Stein Gold, MD1, James Q. Del Rosso, DO2, Leon Kircik, MD3, Neal D. Bhatia, MD4, Deirdre Hooper, MD5, Walter Nahm, MD, PhD6, Iain Stuart, PhD7
 1Henry Ford Health System, Detroit, MI; 2JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 3Icahn School of Medicine at Mount Sanai, New York, NY; 4Therapeutics Clinical Research, San Diego, CA; 5Delricht Research, New Orleans, LA; 6University of California, San Diego School of Medicine, San Diego, CA; 7Menlo Therapeutics Inc., Bridgewater, NJ

Introduction
• Rosacea is a chronic, inflammatory disorder involving the face that is 

characterized by central facial erythema, flushing, telangiectasia, edema, 
papules, and pustules1-3

• Oral tetracyclines, such as doxycycline and minocycline, are among  
the common therapies that are used for treating the disorder with oral,  
sub-microbial doxycycline currently approved for this indication. However,  
these agents have been associated with antibiotic resistance, adverse side 
effects, such as gastrointestinal upset and permanent hyperpigmentation,  
and following treatment cessation, the tendency for disease relapse is high3-7

• The efficacy and safety of FMX103 1.5% topical minocycline foam in treating 
moderate-to-severe rosacea have previously been reported in two, 12-week, 
double-blind, vehicle-controlled, Phase 3 studies (Study 11 and Study 12)8 

• Objective: To demonstrate the long-term safety, tolerability and efficacy 
of topical FMX103 1.5% minocycline foam in moderate to severe facial 
papulopustular rosacea for up to 52 weeks.

Methods
• FX2016-13 (Study 13) was an open-label, multicenter, 40-week extension 

study to evaluate the long-term safety, tolerability, and efficacy of FMX103 
1.5% topical foam in the treatment of moderate-to-severe facial papulopustular 
rosacea (Figure 1)

• Subjects were eligible to enter Study 13 upon successful completion of either 
double-blind study (Study 11 or Study 12)

 – There was no limit on the number of subjects who could enter the  
open-label phase

• Concomitant use of prescription or OTC medications that the subjects were 
taking or any change in dosage was permitted and recorded

• Investigator Global Assessments (IGAs) were based upon a 5-point scale with 
0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe

Figure 1. Study design

Week 52Baseline

Key Inclusion Criteria for DB Study
• Males and nonpregnant females ≥18 years
• Moderate-to-severe facial papulopustular rosacea (IGA 

score of 3 or 4)
• >15 to ≤75 facial papules and pustules, excluding lesions 

involving eyes and scalp; ≤2 nodules on the face
• Presence or history of facial erythema or flushing

Co-Primary Efficacy Endpoints
• Absolute change in the inflammatory lesion count at Week 52 compared to DB 

baseline
• IGA Success Rate (dichotomized as yes/no) at Week 52, where success was 

defined as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) 
from DB baseline

Secondary Efficacy Endpoints
• The absolute and percent change from DB baseline in inflammatory lesion count at 

Weeks 16, 22, 28, 34, 40, 46, and 52 of the OL study
• The dichotomized IGA Success Rate at Weeks 16, 22, 28, 34, 40, and 46
• The Subject Satisfaction Questionnaire (SSQ) at Week 52

Week 12

FMX103 1.5%
(505 enrolled, 504 in safety population, 410 completed)

Double-blind, vehicle-controlled (N=1522)

Open-Label (FX2016-13) for subjects who completed the DB study

Visit every 6 weeks

Vehicle Foam (n=256)

FMX103 1.5% (n=495)

Vehicle Foam (n=257)

FMX103 1.5% (n=514)

S
tu

dy
 1

1
S

tu
dy

 1
2

IGA, Investigator’s Global Assessment; DB, double-blind study; OL, open-label study; OTC, over-the-counter.

Results
Subject Disposition and Double-Blind Baseline Demographics
• As shown in Figure 2, 504 subjects who completed the DB study (Study 11: 

N=217; Study 12: N=287) comprised the All Treated (Safety) population in the 
OL extension study (Study 13)

Figure 2. Subject disposition

3

Discontinuation
Adverse event = 5
Abnormal laboratory follow-up = 0
Lost to follow-up = 29
Subject request = 50
Protocol deviation = 0
Other = 9Completed OL study (N=410)

FMX103/FMX103, n=276 (83%)
Vehicle/FMX103, n=134 (78%)

Study 11
Randomized (N=751)

Completed DB study (FMX103 1.5%) 
n=437

Completed DB study (Vehicle) 
n=232

Entered OL study 
n=140 (32%)

Entered OL study
n=77 (24%)

Study 12
Randomized (N=771)

Completed DB study (FMX103 1.5%) 
n=479

Completed DB study (Vehicle) 
n=239

Entered OL study
n=192 (40%)

Entered OL study
n=95 (40%)

Study 13
Total entering OL study (N=505*)
Total in safety population (N=504)

FMX103/FMX103, n=332 (36%)
Vehicle/FMX103, n=172 (37%)

*One subject who was enrolled discontinued the same day prior to taking the study drug and was therefore excluded from the safety population. 

• Double-blind demographics, double-blind baseline characteristics, and 
concomitant use of medication during the OLE study are shown in Table 1

Table 1. Double-blind baseline demographics, disease characteristics, and 
concomitant use of medication

Variable
FMX103/ 
FMX103
(N=332)

Vehicle Foam/
FMX103
(N=172)

Overall
(N=504)

Mean age (SD)
18 to 40 years
41 to 64 years
≥ 65 years

51.1 (12.62)
68 (20.5)
214 (64.5)
50 (15.1)

51.9 (11.90)
26 (15.1)
121 (70.3)
25 (14.5)

51.4 (12.37)
94 (18.7)
335 (66.5)
75 (14.9)

Gender, n (%)
Male
Female

 
91 (27.4)
241 (72.6)

 
62 (36.0)
110 (64.0)

153 (30.4)
351 (69.6)

Race, n (%) 
White
Black
Other

321 (96.7)
5 (1.5)
6 (1.8)

163 (95.3)
3 (1.8)
6 (1.8)

484 (96.2)
8 (1.6)
12 (2.4)

Mean inflammatory lesion count, n (SD) 28.8 (12.63) 28.7 (11.93) 28.8 (12.38)
IGA score, n (%)

3 – Moderate
4 – Severe

301 (90.7)
31 (9.3)

149 (86.6)
23 (13.4)

450 (89.3)
54 (10.7)

Any concomitant medication during the study, n (%)
Vitamins
Lipid modifying agents
Agents acting on the renin-angiotensin system
Antibiotics and chemotherapeutics for  
dermatological use
Antifungals for dermatological use
Other dermatological preparations

273 (82.2)
81 (24.4)
76 (22.9)
72 (21.7)
6 (1.8)
6 (1.8)
9 (2.7)

137 (79.7)
39 (22.7)
38 (22.1)
35 (20.3)
4 (2.3)
1 (0.6)
3 (1.7)

410 (81.3)
120 (23.8)
114 (22.6)
107 (21.2)
10 (2.0)
7 (1.4)
12 (2.4)

Baseline is defined as the Baseline visit in the double-blind study; IGA, Investigator’s Global Assessment; SD, standard deviation.

Safety and Tolerability
• Summary of all adverse events in the all treated population is shown in Table 2
• The majority of the treatment-emergent adverse events (TEAEs) were considered 

mild or moderate in severity and no serious TEAEs were related to treatment 

Table 2. Summary of TEAEs, rates of discontinuation and overall FMX103 1.5% 
treatment duration in the OL extension

Variable
FMX103 1.5%/ 
FMX103 1.5%

(N=332)

Vehicle Foam/ 
FMX103 1.5%

(N=172)
Overall
(N=504)

Subjects with any AE, n (%) 151 (45.5) 70 (40.7) 221 (43.8)
Subjects with any TEAE, n (%) 137 (41.3) 64 (37.2) 201 (39.9)
Subjects with any serious TEAE, n (%) 9 (2.7)a 4 (2.3)b 13 (2.6)
Subjects with treatment-related TEAEs, n (%) 5 (1.5)c 8 (4.7)d 13 (2.6)
Subjects with serious treatment-related  
TEAEs, n (%) 0 (0.0) 0 (0.0) 0 (0.0)

Subjects discontinued due to AE, n (%) 3 (0.9)e 2 (1.2)f 5 (1.0)
TEAEs resulting in death, n (%) 0 (0.0) 0 (0.0) 0 (0.0)
Subjects exposed to > 6 months (>168 days), n (%) 319 (96.1) 146 (84.9) 465 (92.3)
Subjects exposed to > 1 year (>350 days), n (%) 272 (81.9) 0 (0.0) 272 (54.0)

Number (%) of subjects with at least 1 AE per category; AE, adverse event; TEAE, treatment-emergent adverse event
aLabyrinthitis, periorbital cellulitis, pneumonia, staphylococcal infection, cerebrospinal fluid leakage, cerebrovascular accident, syncope, subdural hematoma, death, hypokalemia, malignant melanoma
bAppendicitis perforated, post procedural hemorrhage, large intestinal instruction, chronic obstructive pulmonary disease
cMydriasis, angular cheilitis, herpes simplex, dermatitis contact, hair color changes
dDiarrhea, conjunctivitis, sunburn, acne, dermatitis contact, erythema, pruritus, rosacea, skin lesion
eDermatitis contact, mydriasis, enchondromatosis
fRosacea, anemia, leukocytosis, appendicitis perforated, sepsis, appendicectomy

• TEAEs occurring in at least 2% of open-label subjects from either arm of the 
double-blind phase are shown in Table 3

Table 3. TEAEs in the OL extension

Variable
FMX103 1.5%/ 
FMX103 1.5%

(N=332)

Vehicle Foam/ 
FMX103 1.5%

(N=172)
Overall
(N=504)

Subjects with one or more TEAE, n (%) 137 (41.3) 64 (37.2) 201 (39.9)
Infections and infestations

Upper respiratory tract infection
Viral upper respiratory tract infection
Sinusitis
Influenza
Bronchitis
Urinary tract infection

14 (4.2)
14 (4.2)
8 (2.4)
9 (2.7)
8 (2.4)
8 (2.4)

5 (2.9)
5 (2.9)
9 (5.2)
5 (2.9)
2 (1.2)
1 (0.6)

19 (3.8)
19 (3.8)
17 (3.4)
14 (2.8)
10 (2.0)
9 (1.8)

Nervous system disorders
Headache

 
8 (2.4) 2 (1.2) 10 (2.0)

Vascular disorders
Hypertension 7 (2.1) 1 (0.6) 8 (1.6)

TEAE, treatment-emergent adverse event

• Local facial assessments at Week 52 demonstrated that FMX103 1.5% topical 
minocycline foam was well tolerated during the OL extension study (Figure 3)

Figure 3. Facial tolerability assessed at Week 52

0

14.2
3.8

0.2

45.1

29.0

29.4

66.3

10.7

0%

25%

50%

75%

100%

BL Wk 52

Erythema

1.5 0.5 1.0 0.70.5 0.4
Chart Title0=None 1=Mild 2=Moderate 3=Severe

6.0
19.0

64.7

97.0

17.1

57.6
45.2

80.3

53.6

86.3

62.1

90.0

62.1

79.1
57.5

66.3

23.4

3.0

42.3

36.9

38.3

18.2

35.3

13.2

30.6

9.0

30.6

20.2

36.5

14.7 11.9

36.9

5.0
16.5

10.7 7.3 7.3
3.8

0%

25%

50%

75%

100%

BL Wk 52 BL Wk 52 BL Wk 52 BL Wk 52 BL Wk 52 BL Wk 52 BL Wk 52

%
 o

f p
op

ul
at

io
n

Hyper-
pigmentation

Peeling/
Desquamation

ItchingDryness/
Xerosis

Flushing/
Blushing

Burning/
Stinging

Telangiectasia

Clear

Severe

Moderate

Mild

Almost Clear

0.8 0.5

Note: Percentages exclude missing responses as 60 responses were missing from the FMX103/FMX103 group (N=272) and 43 responses were missing from the Vehicle/FMX103 group (N=129).
BL refers to baseline of the double-blind study
Hyperpigmentation was evaluated as post-inflammatory hyperpigmentation

Long-Term Efficacy
• Treatment with FMX103 1.5% during the 40-week OL extension study was 

associated with reduction in inflammatory lesions relative to the DB and OL 
baselines, regardless of previous treatment during the DB studies (Figure 4)

Figure 4. Absolute (A) and percent (B) change from DB baseline in 
inflammatory lesions

-100

-75

-50

-25

0
0 4 8 12 16 22 28 34 40 46 52

%
  r

ed
uc

tio
n 

fr
om

 D
B

 b
as

el
in

e 
in

 
in

fla
m

m
at

or
y 

le
si

on
 c

ou
nt

-25

-20

-15

-10

-5

0
0 4 8 12 16 22 28 34 40 46 52

M
ea

n 
re

du
ct

io
n 

fr
om

 D
B

 b
as

el
in

e 
in

 in
fla

m
m

at
or

y 
le

si
on

 c
ou

nt

DB study Vehicle group switched to 
active treatment

FMX103 1.5%/FMX103 1.5% 
(N=332)

BA

-46.4%

- 62.4%

- 80.9%
- 83.0%

Vehicle/FMX103 1.5% 
(N=172)

DB study Vehicle group switched to 
active treatment

FMX103 1.5%/FMX103 1.5% 
(N=332)

-12.8

- 17.9

Vehicle/FMX103 1.5% 
(N=172)

-22.5
-23.0

Week Week

DB, double-blind study; change from baseline is calculated as the value at baseline minus the post-baseline value

• At the end of the study, 81.6% of the FMX103/FMX103 patients, and 76.0% of 
the vehicle/FMX103 patients, achieved IGA treatment success (Figure 5)

Figure 5. IGA treatment success

0

19

37.8

47.6
50.6

60.1
68.1 69.1

72.4
73.5

81.6

0.0

12.2

32.6
39.0

48.2
54.5

64.0 64.4 65.9
72.1

76.0

0

25

50

75

100

0 4 8 12 16 22 28 34 40 46 52

%
 o

f p
op

ul
at

io
n 

w
ith

 
IG

A
 t

re
at

m
en

t s
uc

ce
ss

Week

FMX103/FMX103 Vehicle/FMX103

Number of subjects remaining in the study

Week 0 4 8 12 16 22 28 34 40 46 52

FMX103/
FMX103 332 332 331 332 326 321 310 298 286 279 272

Vehicle/
FMX103 172 172 172 172 168 156 150 146 138 136 129

DB study

*

DB, double-blind study; IGA, Investigator’s Global Assessment
*Week 12 of the DB study serves as the baseline for the OLE study

Subject Satisfaction
• At the end of the open-label study there was a high rate of subject satisfaction 

with FMX103 1.5% for the treatment of papulopustular rosacea (Figure 6)

Figure 6. Subject satisfaction questionnaire results at Week 52 
All Treated Population, N=504

Compared to other products

55%28%

11%

5%

1%

59%24%

11%

5%

1%

Overall satisfaction with product

59%24%

9%

7%

1%

Recommend to friend

Very satisfied

Very dissatisfiedDissatisfied

Somewhat satisfiedSatisfied Very likely

Very unlikelyUnlikely

Somewhat likelyLikely

Percentages exclude 110 missing responses

Summary
Limitations
• Because of the nature of the open-label study, no inference can be made on 

comparability due to the absence of a vehicle-treated control

Conclusions
• FMX103 1.5% appeared to be safe and well tolerated for the long-term treatment of 

papulopustular rosacea for up to 52 weeks of treatment
• No minocycline-induced hyperpigmentation was observed
• Throughout 52 weeks of treatment, FMX103 1.5% continued to be associated with a 

decreasing number of inflammatory lesions, as well as with improvement in overall 
disease severity, as assessed by IGA scores

• Patient satisfaction levels were high, with >80% of all subjects being either satisfied 
or very satisfied with FMX103 1.5%

Disclosures/Acknowledgment
Disclosures 
Dr. Stein Gold is an advisor and investigator for Foamix, Galderma, LEO Pharma, Novartis, and Valeant and is an investigator for Janssen, AbbVie, and Solgel and an 
advisor and investigator for Novartis. 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 SunPharma. Dr. Bhatia is an 
investigator and consultant for Foamix Pharmaceuticals. Dr. Hooper served as an investigator for Foamix Pharmaceuticals; she reports personal fees from DelRicht 
Research during the conduct of the study; honoraria from Allergan, Almirall Aesthetics, Aqua Galderma USA, Cutera, Inc., Ferndale, La Roche Posay, Pixacore, RBC 
Consultants (clarisonic), Revance, and Viviscal; and other financial benefits from Actavis, Dermira, GSK, Mylan, and Sol Gel. Dr. Nahm is an investigator for Foamix 
Pharmaceuticals. Dr. Iain Stuart is an employee and stockholder at Menlo Therapeutics Inc. This study is funded by Foamix Pharmaceuticals Ltd, a wholly owned 
subsidiary of Menlo Therapeutics Inc. 

Acknowledgment
Editorial support was provided by Scient Healthcare Communications.

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