Background
• Acne vulgaris (AV) is a common skin disease that affects adolescents and can persist 

into adulthood1

• The mainstay of treatment for AV is systemic tetracyclines, such as doxycycline and 
minocycline2

• FMX101 4% is a novel topical foam formulation of minocycline. It has been shown to 
be an effective and well-tolerated treatment for moderate-to-severe AV in a Phase 2 
clinical trial3

• Two Phase 1 studies were conducted to characterize minocycline pharmacokinetics 
(PK) and safety following multiple-dose administration of FMX101 4% minocycline 
foam in adult (Study FX2014-03) and pediatric (Study FX2016-21) patients with 
moderate-to-severe AV

Methods
• 2 Phase 1, single-center, nonrandomized, open-label studies (Figure 1, Table 1)

• Adults (age 18 to 35 years) or pediatric subjects (age 9 years to 16 years, 11 months) 
with moderate-to-severe AV

 – Adult Study 
(FX2014-03)

First received a single 1-mg/kg oral dose of oral extended-
release minocycline HCl tablet (Solodyn®). Then, after 10 days, 
they received a once-daily topical application of 4 g FMX101 
4% to the face, neck, upper chest, upper back, shoulders, and 
upper arms for 21 days

 – Pediatric Study 
(FX2016-21)

Received once-daily topical application of 4 g FMX101 4% to 
the face, neck, upper chest, upper back, shoulders, and upper 
arms for 7 days

Figure 1. Study Design

Methods 

Table 1. Inclusion Criteria and Assessments 

Adult Study (FX2014-03) Pediatric Study (FX2016-21)

Inclusion Criteria • Healthy males/females aged  
18–35 years

• Moderate-to-severe facial AV 
(additionally affecting ≥2 regions 
of neck, upper chest, upper back, 
or arms)

• BMI within 18.5-29.9 kg/m2 ; body 
weight within 48.0-128.0 kg

• Not pregnant, lactating, or 
planning a pregnancy during study

• Healthy males/females aged  
9 years to 16 years, 11 months

 – Subjects <12 years: Mild facial 
acne and acne of limited extent

 – Subjects 12–16 years: 
Moderate-to-severe AV based 
on 5-point IGA scale and acne 
affecting ≥1 of the following: 
neck, upper chest, upper back, 
or arms

• Sexually inactive, sterile, or using 
contraception

Blood Sampling 
for Drug 
Concentration

• Predose through 96 hours after 
administration of oral minocycline

• Predose through 24 hours after 
FMX101 4% application on days 1, 
12, and 21

• Prior to scheduled application on 
days 6, 9, 10, 11, and 16

• On and after Day 21, at 24 hours 
(Day 22), 48 hours (Day 23), 72 
hours (Day 24), and 96 hours 
(Day 25) from last application of 
FMX101 4%

• On day 7, after 3, 12, 16, and 
24 hours from last application of 
FMX101 4%

Pharmacokinetic 

Analyses

• PK parameters were calculated 
using noncompartmental methods

• PK parameters included AUC
0-inf,

 
AUC

0-tau
, AUC

0-tldc
, C

max
, C

24
, T

max
, 

T
1/2

, and accumulation ratio

• PK parameters were calculated 
using noncompartmental methods

• PK parameters included AUC
0-tau

, 
C

max
, and C

24
 

Statistical 
Analyses

• Geometric mean was calculated 
for AUC

0-inf
, AUC

0-tau
, AUC

0-tldc
, and 

C
max

• Geometric mean was calculated 
for AUC

0-tau  
and C

max

AUC
0-inf

=AUC from 0 to infinity.
AUC

0-tau
=AUC during the 24-hour dosing interval. 

AUC
0-tldc

=AUC from 0 to time of last determinable concentration. 
C

24
=plasma minocycline concentration 24 hours after FMX101 4% application.

C
max

=maximum plasma drug concentration.
T

1/2
=terminal phase half-life.

T
max

=time of maximum measured plasma drug concentration. 
BMI=body mass index. 
IGA=Investigator’s Global Assessment.

Results
Baseline Demographics
• Baseline characteristics are shown in Table 2

• All adult subjects had moderate-to-severe AV

• A majority of pediatric subjects (90%) had moderate AV, and 1 subject had mild AV

Table 2. Baseline Characteristics

Adult Study  
(FX2014-03)  

(N=30)

 Pediatric Study 
(FX2016-21) 

(N=20)

Mean age (range), yr 22.6 (18-30) 13.2 (10-16)

Gender, n (%)
Male/Female 12 (40) / 18 (60) 9 (45) / 11 (55)

Race, n (%)
White
Black or African American

27 (90)
3 (10)

7 (35)
13 (65)

Ethnicity, n (%)
Hispanic/Latino
Non-Hispanic/Latino

11 (36.7)
19 (63.3)

2 (10)
18 (90)

Pharmacokinetics – Adults
• The mean plasma concentration of oral minocycline in adult subjects reached C

max
 by 

3 hours after administration, followed by a log-linear decrease in concentration for the 
remaining 96-hour sample period

• The mean plasma minocycline concentration of FMX101 4% increased until 8–14 hours 
(median T

max
 value) on days 1, 12, and 21

• Figure 2 shows a comparison of mean plasma minocycline concentrations during the 
first 24 hours after a single dose of oral minocycline and after topical applications of 
FMX101 4% at 3 timepoints in adult subjects

• In adult subjects, oral minocycline treatment had a geometric mean C
max

 of 850 ng/mL, 
while topical application of 4 g FMX101 4% in adults had a geometric mean C

max
 

ranging from 1.109–1.539 ng/mL (days 1-2, days 12-13, and days 21-25) 

• Steady state was achieved on day 6 of treatment

Figure 2. Mean Plasma Minocycline Concentration Over the First 24 Hours Following 
a Single Dose of Oral Minocycline and Topical Application of FMX101 4% (Semi-log 
Scale) in Adult Subjects (Study FX2014-03)

Results: Pharmacokinetics – Adults

• In adults, minocycline exposure with daily topical application of FMX101 4% for  
21 days was 730 to 765 times lower than that with oral minocycline (Table 3)

Table 3. Summary of Minocycline Relative Bioavailability With Oral Minocycline 
Administration (Reference) and Topical Application of FMX101 4% (Test) at Day 12 
and Day 21 (Study FX2014-03)

FMX101 4%  
vs  
Oral Minocycline N

Geometric Meana

Geometric LSM 
Test/Reference 

Ratio,b % (90% CI) 1/GMR
FMX101 4%

(Test)

Oral 
Minocycline

(Ref)

Day 12 C
max

29 1.06 846 0.126 (0.100, 0.159) 794

Day 21 C
max

30 1.11 850 0.131 (0.113, 0.151) 763

Day 12 AUCc 29 20.06 14976 0.134 (0.110, 0.163) 746

Day 21 AUCd 30 20.07 15060 0.137 (0.121, 0.156) 730

ªGeometric mean of oral minocycline and FMX101 4% based on LSM.
bGeometric LSM ratio and the associated 90% CI were back-transformed point estimates and the 
associated 90% CI.

cDay 12 AUC
0-tau

 for FMX101 4% vs AUC
0-inf

 for oral minocycline.
dDay 21 AUC

0-tau
 for FMX101 4% vs AUC

0-inf
 for oral minocycline.

CI=confidence interval; LSM=least squares mean; GMR=geometric mean ratio.

Pharmacokinetics – Pediatrics
• In pediatric subjects, the overall plasma concentrations of minocycline following the 

application of FMX101 4% once daily for 7 days were relatively constant over day 7 
(~2.5 ng/mL) (Figure 3)

Figure 3. Mean Plasma Concentrations of Minocycline Following Application  
of FMX101 4% Once Daily for 7 Days in Pediatric Subjects (Study FX2016-21)

Results: Pharmacokinetics – Pediatrics

-5

0

5

10

15

20

25

0 3 12 16 24

Pl
as

m
a 

M
in

oc
yc

lin
e 

C
on

ce
nt

ra
tio

n 
(n

g/
m

L)
 ±

SD

Hours Post-Day 7 Administration

9 - 11 years 12 - 14 years 15 - 16 years, 11 months Overall

LLOQ

LLOQ=Lower limit of quantification; SD=Standard deviation.
LLOQ=lower limit of quantification; SD=standard deviation.

• There were no substantial differences in mean concentrations of minocycline among 
the 3 pediatric cohorts (Table 4)

 – Across all cohorts, the geometric mean C
max

 value was 2.4 ng/mL

Table 4. Pharmacokinetic Parameters of Minocycline in Plasma in Pediatric Acne 
Subjects Treated With FMX101 4% (Study FX2016-21)

Age Group N

Geometric Mean

T
max

 (hr)aC
max

 (ng/mL)
AUC

0-tau
 

(ng*hr/mL) C
24

 (ng/mL)

9–11 years 6 3.522 68.175 2.933 12 (0,24)

12–14 years 8 2.250 42.167 1.998 20 (0,24)

15–16 years, 11 months 6 1.735 35.067 1.302 6 (0,24)

Overall 20 2.381 46.087 1.972 12.1 (0,24)
aMedian (minimum, maximum) shown for T

max
.

Safety
• In both adult and pediatric subjects, daily application of FMX101 4% was found to be 

safe and well tolerated (Table 5)

 – No adult or pediatric subjects experienced a serious treatment-emergent adverse 
event (TEAE), treatment-related TEAEs, or a TEAE leading to withdrawal from the 
study

 – 9 adult subjects in the FMX101 4% group reported 1 or more TEAES; all were mild 
or moderate in intensity (FX2014-03) 

 – A single pediatric subject experienced 2 unrelated TEAEs (nausea and vomiting) 
(FX2016-21)

Table 5. Overall Summary of TEAEs Following Administration of Oral Minocycline and 
Topical Application of FMX101 4% in Adult and Pediatric Subjects

Adult Study (FX2014-03)
Pediatric Study 

(FX2016-21)

  Oral Minocycline
(N=30)

FMX101 4% 
(N=30)

FMX101 4%
(N=20)

Subjects with any TEAE, n (%) 2 (6.7) 9 (30.0) 1 (5.0)

Dysmenorrhea 0 2 (6.7) -

Nasal congestion 0 2 (6.7) -

Rhinorrhea 0 2 (6.7) -

Asthma 0 1 (3.3) -

Bronchitis 0 1 (3.3) -

Cough 1 (3.3) 0 -

Dermatitis contact 0 1 (3.3) -

Headache 1 (3.3) 0 -

Oropharyngeal pain 0 1 (3.3) -

Pharyngitis streptococcal 0 1 (3.3) -

Respiratory tract congestion 0 1 (3.3) -

Tonsillitis 0 1 (3.3) -

Nausea - - 1 (5.0)

Vomiting - - 1 (5.0)

Pharmacokinetic Evaluation of Once-Daily Topical 4% Minocycline Foam in Adult and  
Pediatric Subjects With Moderate-to-Severe Acne in Two Phase 1 Studies

Terry M. Jones, MD1; Herman Ellman, MD2; Tina deVries, PhD2
1J&S Studies, Inc., College Station, Texas, USA; 2Foamix Pharmaceuticals, Inc., Bridgewater, New Jersey, USA 

References
1. Picardo M, et al. Dermatol Ther (Heidelb). 2017;7:43-52.
2. Zaenglein AL, et al. J Am Acad Dermatol. 2016;74:945-973.
3. Shemer A, et al. J Am Acad Dermatol. 2016;74:1251-1252. Disclosure: Foamix Pharmaceuticals, Inc., sponsored this study.

Conclusions
• In adult subjects, mean minocycline AUC and C

max
 values were substantially lower 

following the daily topical application of 4 g FMX101 4% for 21 days in comparison 
with a single dose of oral minocycline (~1 mg/kg)  

• There was no evidence of accumulation in adult subjects receiving daily topical 
application of FMX101 4% for up to 21 days 

• In pediatric subjects, mean minocycline Cmax and AUC values following the daily 
topical application of 4 g FMX101 4% for 7 days were 2.4 ng/mL and 46.1 ng*hr/mL, 
respectively; these values were comparable to those seen in adults, 1.5 ng/mL and  
20.1 ng*hr/mL, respectively, indicating similar minimal systemic exposure

• Pediatric subjects in all 3 age cohorts had similar levels of minocycline (~2.5 ng/mL) 
across the dosing interval with daily application of FMX101 4% for 7 days

• Once-daily topical application of FMX101 4% for 7 days and 21 days was shown to be 
safe and well tolerated in pediatric and adult subjects, respectively

Acknowledgment: p-value communications provided editorial support.