Introduction
• Rosacea is a chronic skin condition characterized by erythema, inflammatory 

papules/pustules, or telangiectasia. It is estimated to affect ~16 million people  
in the US1,2

• FDA-approved treatment for rosacea includes topical agents, such as 
metronidazole, azelaic acid, sulfacetamide 10%/sulfur 5%, and, recently, 
ivermectin, as well as oral doxycycline1,3

• Oral tetracyclines, particularly minocycline and doxycycline, may be prescribed 
for moderate-to-severe rosacea; however, their use is associated with systemic 
AEs1,3

• A novel, foam formulation of minocycline – FMX-103 – has been developed to 
facilitate local application and bioavailability of minocycline while preserving its 
efficacy for the treatment of rosacea

• This was a randomized, multicenter, double-blind study evaluating the safety and 
efficacy of 2 different doses of the topical minocycline foam, FMX-103 1.5% and 
3%, in the treatment of papulopustular rosacea, as compared with vehicle 

Methods
• Phase 2, randomized, multicenter (18 sites in Germany), double-blind, vehicle-

controlled clinical trial

• Evaluated the safety and efficacy of 2 doses of a topical once-daily minocycline 
foam (FMX-103 1.5% and 3%) compared with vehicle foam in the treatment of 
moderate-to-severe papulopustular rosacea (Figure 1)

 – Subjects were randomized 1:1:1 to receive treatment once daily  
(in the evening) for 12 weeks

 – Safety and efficacy evaluations were performed at week 2, 4, 8, and 12,  
with an additional safety follow-up visit at week 16 

Figure 1. Study design

Efficacy and safety end points

• Absolute ∆ inflammatory lesion 
count (primary end point)

• IGA: ≥2-grade improvement; 
“clear” or “almost clear” 

• Safety and tolerability
 

N=232a

Week 12Baseline

FMX - 103 3% (once daily) (n=75)

Foam vehicle (once daily) (n=78) 

FMX - 103 1.5% (once daily) (n=79)

Week 16Week 4 Week 8Week 2

Follow-up
period

Inclusion criteria

• Healthy males/nonpregnant 
females, aged ≥18 years

• Moderate-to-severe rosacea for 
≥6 months, with ≥12 inflammatory 
facial lesions (papules/pustules)

R
an

d
o

m
iz

e
d

 1
:1

:1

aA total of 233 subjects were randomized; however, 1 subject in the FMX-103 3% group did not receive 
treatment and was not included in the intent-to-treat analysis.

Results
• 232 subjects were randomized and received at least one dose of study drug  

(ITT population)

 – 201 (86.6%) subjects completed 12 weeks of treatment and the follow-up visit

• Baseline demographics and disease characteristics are shown in Table 1

 – ~50% to 60% of subjects had severe rosacea; the mean number of 
inflammatory lesions ranged from 30.6 to 34.5

Table 1. Baseline demographics and disease characteristics

FMX-103 1.5%
(n=79)

FMX-103 3%
(n=75)

Vehicle
(n=78)

Overall 
(n=232)

Mean age, years (range) 51.2 (21-82) 51.6 (22-78) 54.8 (24-80) 52.5 (21-82)

Gender, %

Male / Female 32.9 / 67.1 32.0 / 68.0 47.4 / 52.6 37.5 / 62.5

Race, %

Caucasian 98.7 97.3 100.0 98.7

Othera 1.3 2.7 0 1.3

IGA of rosacea, %b

Moderate (IGA=3) 43.0 38.7 51.3 44.4

Severe (IGA=4) 57.0 61.3 48.7 55.6

Mean (±SD) total  
inflammatory lesion count 34.5 (±20.89) 34.1 (±24.99) 30.6 (±15.48) 33.1 (±20.74)

an=1 Other (FMX-103 1.5%); n=1 American Indian or Alaska Native, n=1 Native Hawaiian or Other Pacific Islander (FMX-103 3%).
bIGA grading for rosacea: 0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe.

• At week 12, both FMX-103 1.5% and 3% doses significantly reduced the number 
of papules and pustules vs vehicle (P<.001) (Figure 2A)

 – Significant reduction in lesion count was observed as early as week 2

• The corresponding percentage reductions in inflammatory lesions were 61.4% 
and 55.5% for FMX-103 1.5% and 3%, respectively, vs 29.7% for vehicle at  
week 12 (P<.001) (Figure 2B)

Figure 2. Change in inflammatory lesion counts from baseline by visit

FMX-103 1.5% (n=79)
FMX-103 3% (n=75)
Vehicle (n=78)

FMX-103 1.5% (n=79)
FMX-103 3% (n=75)
Vehicle (n=78)

• Significantly more FMX-103 1.5% and 3% subjects achieved ≥2-grade 
improvement in IGA (Figure 3A) and IGA score of “clear” or “almost clear”  
vs vehicle at week 12 (Figure 3B)

 – Significantly more FMX-103 subjects had improvement of ≥2 IGA grades  
as early as week 4

• There was no statistically significant difference between the FMX-103 1.5% and 
3% groups

Figure 3. Improvement in IGA score from baseline by visit

FMX-103 1.5% (n=79)
FMX-103 3% (n=75)
Vehicle (n=78)

FMX-103 1.5% (n=79)
FMX-103 3% (n=75)
Vehicle (n=78)

Safety
• Both FMX-103 1.5% and 3% doses appeared to be generally safe and  

well tolerated, with no reported treatment-related systemic AEs

 – Overall, 47% (109/232) of subjects reported ≥1 TEAE (Table 2)

 – The most common AEs (≥2% of subjects) included nasopharyngitis,  
urinary tract infection, cystitis, and bronchitis (Table 3)

 – 11 (4.7%) subjects reported treatment-related TEAEs; 9 had treatment-
related dermal reactions (Tables 2, 4)

 – Serious TEAEs were reported in 4 subjects (3 in FMX-103 groups and  
1 in vehicle group) (Tables 2, 4)

 – 4 subjects discontinued the study due to TEAEs; only 3 subjects 
discontinued due to dermal-related TEAEs (skin and subcutaneous tissue 
disorders) (Tables 2, 4)

Table 2. Summary of safety profile

Overall Summary of TEAEs, n (%)
FMX-103 1.5%

(n=79)
FMX-103 3%

(n=75)
Vehicle
(n=78)

Subjects with ≥1 TEAE 46 (58.2) 32 (42.7) 31 (39.7)

Subjects with ≥1 treatment-related 
TEAEa 2 (2.5) 4 (5.3) 5 (6.4)

Treatment-related dermal reactionsb,c 1 (1.3) 3 (4.0) 5 (6.4)

Subjects with ≥1 serious TEAE 2 (2.5) 1 (1.3) 1 (1.3)

Subjects with ≥1 TEAE leading to 
study discontinuation 0 3 (4.0) 1 (1.3)

Safety population includes all randomized subjects who applied at least one dose of study drug.
aIncludes unassessable, possible, probable, and certainly related AEs.
bIncludes skin and subcutaneous tissue disorders, and general disorders and administration-site 
conditions (ie, application-site erythema).

cSubjects experiencing ≥1 AE are counted only once for each AE term.

Table 3. Summary of TEAEs in ≥2% of subjects

Common TEAEs (≥2% of subjects),  
n (%)a

FMX-103 1.5%
(n=79)

FMX-103 3%
(n=75)

Vehicle
(n=78)

Nasopharyngitis 11 (13.9) 3 (4.0) 9 (11.5)
Urinary tract infection 3 (3.8) 2 (2.7) 3 (3.8)
Cystitis 2 (2.5) 2 (2.7) 0
Bronchitis 3 (3.8) 0 0
Urinary tract infection bacterial 2 (2.5) 0 0
Influenza 0 0 2 (2.6)
Rosacea 2 (2.5) 3 (4.0) 0
Eczema 2 (2.5) 2 (2.7) 2 (2.6)
Hypertension 2 (2.5) 2 (2.7) 2 (2.6)
Eczema eyelids 2 (2.5) 0 0
Toothache 2 (2.5) 0 0
Headache 0 2 (2.7) 0

Safety population includes all randomized subjects who applied at least one dose of study drug.
aSubjects experiencing ≥1 AE are counted only once for each AE term.

Table 4. Summary of treatment-related dermal reactions, serious TEAEs, and 
TEAEs leading to study discontinuation

FMX-103 1.5%
(n=79)

FMX-103 3%
(n=75)

Vehicle
(n=78)

Subjects with treatment-related dermal 
reactions, n (%)a,b 1 (1.3) 3 (4.0) 5 (6.4)
Rosacea 0 2 (2.7) 0
Eczema 0 1 (1.3) 1 (1.3)
Skin exfoliation 0 1 (1.3) 0
Erythema 0 0 1 (1.3)
Pruritus 0 0 1 (1.3)
Scab 0 0 1 (1.3)
Skin burning sensation 0 0 1 (1.3)
Application-site erythema 1 (1.3) 0 1 (1.3)
Subjects with ≥1 serious TEAE, n (%)b 2 (2.5) 1 (1.3) 1 (1.3)
Hemorrhoids 0 1 (1.3) 0
Contusion 1 (1.3) 0 0
Cerebral hemorrhage 1 (1.3) 0 0
Hemiparesis 1 (1.3) 0 0
Pulmonary embolism 1 (1.3) 0 0
Gastroenteritis 0 0 1 (1.3)
Subjects with ≥1 TEAE leading to study 
discontinuation, n (%)b,c 0 3 (4.0) 1 (1.3)
Eczema 0 1 (1.3) 0
Rosacea 0 1 (1.3) 0
Pruritus 0 0 1 (1.3)
Skin burning sensation 0 0 1 (1.3)
Burning sensation 0 1 (1.3) 0

Safety population includes all randomized subjects who applied at least one dose of study drug.
aIncludes skin and subcutaneous tissue disorders, and general disorders and administration-site 
conditions (application-site erythema).

bSubjects experiencing ≥1 AE are counted only once for each AE term.
cEczema, rosacea, pruritus, and skin burning sensation were classed as skin and subcutaneous tissue 
disorders (dermal related); burning sensation was classified as a nervous system disorder.

Conclusions
• At week 12, both FMX-103 1.5% and FMX-103 3% were significantly better 

than vehicle in

 – Reducing the number of papules and pustules
 – Improving IGA score by ≥2 grades
 – Achieving IGA of “clear” or “almost clear” (score 0 or 1)

• Both FMX-103 doses appeared to be generally safe and well tolerated,  
with no reported treatment-related systemic AEs

 – Only 3 subjects discontinued the study due to dermal-related TEAEs

• These results indicated that FMX-103 appeared to be an effective, safe,  
and well tolerated treatment for moderate-to-severe papulopustular rosacea

• The results support further investigation in a larger, Phase 3 clinical trial

References
1. Oge LK, et al. Am Fam Physician. 2015;92:187-196.
2. National Rosacea Society. Rosacea Review. www.rosacea.org/rr/2010/winter/article_1.php. 

Accessed December 5, 2016.
3. American Acne & Rosacea Society. Rosacea Medical Management Guidelines.  

www.acneandrosacea.org/sites/default/files/AARS_Rosacea_Guidelines_2007.pdf.  
Accessed December 5, 2016.

Abbreviations: 
AE=adverse event; TEAE=treatment emergent adverse event;  
IGA=Investigator’s Global Assessment; ITT=intent-to-treat; SD=standard deviation.
Disclosure: Foamix Pharmaceuticals, Inc., sponsored this study.
Acknowledgment: Editorial support was provided by Giang Nguyen, PhD,  
of p-value communications.

Topical Minocycline Foam (FMX-103) for the Treatment of Moderate-to-Severe Rosacea:  
Results of a Phase 2, Randomized, Double-Blind, Multicenter Clinical Study

Ulrich Mrowietz1, Tal Hetzroni Kedem2, Rita Keynan2, Meir Eini2, Dov Tamarkin2, Mitchell Shirvan2
1University Medical Center Schleswig-Holstein, Campus Kiel, Germany; 2Foamix Pharmaceuticals, Ltd., Rehovot, Israel. 


	FC17PosterFoamixMrowietzTopicalMinocyclineRosacea.pdf