A Study (Study 1) to Evaluate the Safety and Efficacy of FMX103 1.5% Topical Minocycline Foam in the Treatment of Facial Papulopustular Rosacea

• Sponsor: Vyne Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03142451
• Collaborator: Premier Research Group plc (Industry)
• Enrollment: 751
• Locations: 54
• Arms: 2
• Actual Duration (Months): 15.9
• Patients Per Site: 13.9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The primary objectives of this study are to determine the efficacy and safety of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea.

Condition or Disease	Intervention/Treatment	Phase
Facial Papulopustular Rosacea	Drug: FMX103 minocycline foam 1.5%; Drug: Vehicle foam	Phase 3

Detailed Description

This is a randomized, multicenter, double-blind, vehicle-controlled, 2 arm study to evaluate the safety and efficacy of FMX103 topical foam containing 1.5% minocycline compared to vehicle, in the treatment of participants with moderate-to-severe facial papulopustular rosacea. Qualified participants will be randomized in a 2:1 ratio (active:vehicle) to receive 1 of the following 2 treatments:

• FMX103 minocycline foam 1.5%

• Vehicle foam

Participants will be assigned to 1 of 2 treatments according to the randomization schedule. Participants will apply (or have applied) the study drug topically once daily for 12 weeks as directed. Participants will be advised to use the study drug at approximately the same time each day. Both the Investigator and participant will be blinded to the study drug identity. Participants will return for visits at Weeks 1, 4, 6, 8, 10, and 12. Efficacy evaluations (inflammatory lesion counts and Investigator's Global Assessment [IGA] score) will be performed at Weeks 4, 8, and 12 during the study.

Note: Originally the two studies FX2016-11 and FX2016-12 were combinedly presented in the protocol registration form under one NCT number (NCT03142451), and later separated since results were analyzed separately.

Study Design

• Study Type: Interventional
• Actual Enrollment: 751 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: This is a double-blind study, with limited access to the randomization code. The randomization code will be held in confidence until after the study database is locked and a memo documenting the database lock has been issued. Every effort will be made to retain the integrity of the blind. When issued to the sites, the study drug will be identical in appearance for all participants, regardless of treatment assignment.
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Double-blind, Vehicle-controlled Study to Evaluate the Safety and Efficacy of FMX103 1.5% Topical Minocycline Foam Compared to Vehicle in the Treatment of Facial Papulopustular Rosacea (FX2016-11)
• Actual Study Start Date: Jun 2, 2017
• Actual Primary Completion Date: Aug 31, 2018
• Actual Study Completion Date: Sep 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FMX103 1.5% Participants will apply the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Drug: FMX103 minocycline foam 1.5%; Dosage form description: Foam containing minocycline HCl 1.5%. Once daily application of a sufficient amount of foam to cover the entire face. Estimated maximum is 0.5 g of drug product containing 7.5 mg (1.5% active) of minocycline. Participants will apply a small amount of the drug as a thin layer over all areas of the face. Participants should apply the drug at approximately the same time each day, about 1 hour before bedtime.
Placebo Comparator: Vehicle foam Participants will apply the assigned vehicle foam topically once daily for 12 weeks as directed.	Drug: Vehicle foam; Dosage form description: Foam containing minocycline vehicle foam. Once daily application of a sufficient amount of foam to cover the entire face. Estimated maximum is 0.5 g of drug product containing 0.0 mg (vehicle) of minocycline. Participants will apply a small amount of the drug as a thin layer over all areas of the face. Participants should apply the drug at approximately the same time each day, about 1 hour before bedtime.

Outcome Measures

Primary Outcome Measures

1. The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Count at Week 12 [Baseline and Week 12]

   To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count.

2. Percentage of Participants Achieving Investigator Global Assessments (IGA) Treatment Success at Week 12 [Week 12]

   To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-step improvement (decrease) from Day 0/Baseline.

Secondary Outcome Measures

1. Percentage of Participants Achieving IGA Treatment Success of at Least 2 Grades at Week 12 [Week 12]

   To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as a 2-grade improvement (decrease) in score at Week 12 compared to Day 0/Baseline. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.

2. The Percent Change From Day 0/Baseline in Inflammatory Lesion Count at Week 12 [Baseline and Week 12]

   To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.

3. The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8 [Baseline, Week 4 and Week 8]

   To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. The change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count.

4. Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8 [Week 4 and Week 8]

   To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Day 0/Baseline.

5. Number of Participants With Adverse Events (AEs) [From Day 0/Baseline until the Safety Follow-up (4 weeks after Week 12 [Final Visit])]

   To evaluate the tolerability and safety of topical minocycline foam applied once daily for 12 weeks. A treatment-emergent adverse events (TEAE) was defined as any AE with an onset date on or after the first application of study drug, and before to the last application of study drug plus 3 days, having been absent pre-treatment or worsening relative to the pre-treatment state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Moderate-to-severe rosacea (as per the IGA score) on the proposed facial treatment area consisting of:

2. At least 15 and not more than 75 facial papules and pustules, excluding lesions involving the eyes and scalp;

3. No more than 2 nodules on the face.

4. Presence of or history of erythema and/or flushing on the face.

Exclusion Criteria:

1. Presence of any skin condition and/or Excessive facial hair, on the face that would interfere with the diagnosis or assessment of rosacea.

2. Moderate or severe rhinophyma, dense telangiectasia (score 3, severe), or plaque-like facial edema.

3. History of hypersensitivity or allergy to minocycline, any other tetracycline, or of any other component of the formulation.

4. Active ocular rosacea (eg, conjunctivitis, blepharitis, or keratitis) of sufficient severity to require topical or systemic antibiotics.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Foamix Investigational Site #152	Tucson	Arizona	United States	85712
2	Foamix Investigational Site # 127	Fremont	California	United States	94538
3	Foamix Investigational Site #155	Los Angeles	California	United States	90036
4	Foamix Investigational Site #143	Northridge	California	United States	91324
5	Foamix Investigational Site # 131	Oceanside	California	United States	92056
6	Foamix Investigational Site #156	Oceanside	California	United States	92056
7	Foamix Investigational Site #153	San Diego	California	United States	92103
8	Foamix Investigational Site # 114	San Diego	California	United States	92123
9	Foamix Investigational Site # 116	San Luis Obispo	California	United States	93405
10	Foamix Investigational Site # 135	Santa Ana	California	United States	92705
11	Foamix Investigational Site # 123	Santa Monica	California	United States	90403
12	Foamix Investigational Site # 109	Clearwater	Florida	United States	33757
13	Foamix Investigational Site # 112	Hialeah	Florida	United States	33016
14	Foamix Investigational Site #150	Lake Worth	Florida	United States	33467
15	Foamix Investigational Site #144	Miami Lakes	Florida	United States	33016
16	Foamix Investigational Site #149	Miami	Florida	United States	33126
17	Foamix Investigational Site #151	Miami	Florida	United States	33144
18	Foamix Investigational Site # 104	Ormond Beach	Florida	United States	32174
19	Foamix Investigational Site # 121	Sanford	Florida	United States	32771
20	Foamix Investigational Site #154	Sweetwater	Florida	United States	33172
21	Foamix Investigational Site # 125	Tampa	Florida	United States	33609
22	Foamix Investigational Site # 142	West Palm Beach	Florida	United States	33406
23	Foamix Investigational Site # 124	West Palm Beach	Florida	United States	33409
24	Foamix Investigational Site # 118	Alpharetta	Georgia	United States	30022
25	Foamix Investigational Site # 139	Snellville	Georgia	United States	30078
26	Foamix Investigational Site # 138	New Albany	Indiana	United States	47150
27	Foamix Investigational Site # 102	Metairie	Louisiana	United States	70006
28	Foamix Investigational Site # 115	New Orleans	Louisiana	United States	70115
29	Foamix Investigational Site # 110	Beverly	Massachusetts	United States	01915
30	Foamix Investigational Site # 107	Brighton	Massachusetts	United States	02135
31	Foamix Investigational Site # 137	Ann Arbor	Michigan	United States	48103
32	Foamix Investigational Site # 103	Fort Gratiot	Michigan	United States	48059
33	Foamix Investigational Site # 120	Troy	Michigan	United States	48084
34	Foamix Investigational Site # 140	Warren	Michigan	United States	48088
35	Foamix Investigational Site # 130	Saint Joseph	Missouri	United States	64506
36	Foamix Investigational Site # 133	Omaha	Nebraska	United States	68144
37	Foamix Investigational Site #146	Las Vegas	Nevada	United States	89148
38	Foamix Investigational Site # 136	New York	New York	United States	10075
39	Foamix Investigational Site #145	New York	New York	United States	10155
40	Foamix Investigational Site # 111	Stony Brook	New York	United States	11790
41	Foamix Investigational Site # 119	Charlotte	North Carolina	United States	28277
42	Foamix Investigational Site # 101	Bexley	Ohio	United States	43209
43	Foamix Investigational Site # 128	Dublin	Ohio	United States	43016
44	Foamix Investigational Site #147	Broomall	Pennsylvania	United States	19008
45	Foamix Investigational Site # 141	Jenkintown	Pennsylvania	United States	19046
46	Foamix Investigational Site #157	Saint Clair	Pennsylvania	United States	15241
47	Foamix Investigational Site # 129	Yardley	Pennsylvania	United States	19067
48	Foamix Investigational Site # 105	Johnston	Rhode Island	United States	02919
49	Foamix Investigational Site # 106	Greenville	South Carolina	United States	29607
50	Foamix Investigational Site # 122	Murfreesboro	Tennessee	United States	37130
51	Foamix Investigational Site # 117	Austin	Texas	United States	78759
52	Foamix Investigational Site #159	Houston	Texas	United States	77074
53	Foamix Investigational Site # 108	San Antonio	Texas	United States	78213
54	Foamix Investigational Site # 126	Salt Lake City	Utah	United States	84117

Sponsors and Collaborators

• Vyne Therapeutics Inc.
• Premier Research Group plc

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 12, 2017
• Statistical Analysis Plan - Jul 31, 2018

More Information

Publications

None provided.

• Responsible Party: Vyne Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03142451
• Other Study ID Numbers: FX2016-11
• First Posted: May 5, 2017
• Last Update Posted: Jan 29, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Vyne Therapeutics Inc.: Topical Minocycline Foam; 2-Arm study; Inflammatory lesion counts; Investigator's Global Assessment score
• Additional relevant MeSH terms: Rosacea; Facies; Minocycline

Study Results

Participant Flow

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Period Title: Overall Study
STARTED	495	256
COMPLETED	437	232
NOT COMPLETED	58	24

Baseline Characteristics

Arm/Group Title	FMX103 1.5%	Vehicle Foam	Total
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.	Total of all reporting groups
Overall Participants	495	256	751
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.9 (13.71)	49.7 (12.85)	49.2 (13.42)
Sex: Female, Male (Count of Participants)
Female	355 71.7%	186 72.7%	541 72%
Male	140 28.3%	70 27.3%	210 28%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	165 33.3%	88 34.4%	253 33.7%
Not Hispanic or Latino	328 66.3%	168 65.6%	496 66%
Unknown or Not Reported	2 0.4%	0 0%	2 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 0.6%	0 0%	3 0.4%
Asian	6 1.2%	6 2.3%	12 1.6%
Native Hawaiian or Other Pacific Islander	3 0.6%	3 1.2%	6 0.8%
Black or African American	7 1.4%	4 1.6%	11 1.5%
White	474 95.8%	241 94.1%	715 95.2%
More than one race	2 0.4%	1 0.4%	3 0.4%
Unknown or Not Reported	0 0%	1 0.4%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Count at Week 12
Description	To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Measure Participants	495	256
Mean (Standard Error) [Lesions]	17.56 (0.442)	15.34 (0.604)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA) model includes treatment, baseline inflammatory lesion count, and analysis center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.21
	Confidence Interval	(2-Sided) 95%; 0.75 to 3.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.749
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Achieving Investigator Global Assessments (IGA) Treatment Success at Week 12
Description	To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-step improvement (decrease) from Day 0/Baseline.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Measure Participants	495	256
Number [Percentage of participants]	52.1 10.5%	43.0 16.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0273
	Comments	The p-value is for the null hypothesis that the combined risk ratio equals 1.
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel Test Stratified by Analysis Center
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.210
	Confidence Interval	(2-Sided) 95%; 1.022 to 1.434
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Achieving IGA Treatment Success of at Least 2 Grades at Week 12
Description	To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as a 2-grade improvement (decrease) in score at Week 12 compared to Day 0/Baseline. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Measure Participants	423	225
Number [Percentage of participants]	55.3 11.2%	45.8 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0171
	Comments	The p-value is for the null hypothesis that the combined risk ratio equals 1.
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel Test Stratified by Analysis Center
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.210
	Confidence Interval	(2-Sided) 95%; 1.028 to 1.425
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	The Percent Change From Day 0/Baseline in Inflammatory Lesion Count at Week 12
Description	To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Measure Participants	423	225
Least Squares Mean (Standard Error) [Percent change]	64.13 (1.584)	56.52 (2.133)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments
	Method	ANCOVA
	Comments	ANCOVA model includes treatment, Baseline inflammatory lesion count, and analysis center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.62
	Confidence Interval	(2-Sided) 95%; 2.46 to 12.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.626
	Estimation Comments

5. Secondary Outcome

Title	The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8
Description	To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. The change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count.
Time Frame	Baseline, Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Measure Participants	495	256
Week 4	11.24 (0.441)	8.62 (0.608)
Week 8	15.59 (0.445)	12.51 (0.610)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments	Statistical analysis for Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included treatment, Baseline inflammatory lesion count, and analysis center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.63
	Confidence Interval	(2-Sided) 95%; 1.16 to 4.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.747
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments	Statistical analysis for Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included treatment, Baseline inflammatory lesion count, and analysis center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.09
	Confidence Interval	(2-Sided) 95%; 1.62 to 4.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.750
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8
Description	To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Day 0/Baseline.
Time Frame	Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Measure Participants	495	256
Week 4	15.3 3.1%	9.1 3.6%
Week 8	35.2 7.1%	29.4 11.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments	Statistical analysis for Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0201
	Comments	P-value is for the null hypothesis that the risk ratio equals 1.
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test stratified by analysis center.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.685
	Confidence Interval	(2-Sided) 95%; 1.085 to 2.616
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FMX103 1.5%, Vehicle Foam
	Comments	Statistical analysis for Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1278
	Comments	P-value is for the null hypothesis that the risk ratio equals 1.
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test stratified by analysis center.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.191
	Confidence Interval	(2-Sided) 95%; 0.951 to 1.492
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	To evaluate the tolerability and safety of topical minocycline foam applied once daily for 12 weeks. A treatment-emergent adverse events (TEAE) was defined as any AE with an onset date on or after the first application of study drug, and before to the last application of study drug plus 3 days, having been absent pre-treatment or worsening relative to the pre-treatment state.
Time Frame	From Day 0/Baseline until the Safety Follow-up (4 weeks after Week 12 [Final Visit])

Outcome Measure Data

Analysis Population Description

The Safety (SAF) population included all randomized participants who used at least 1 dose of study drug, including participants who had no post-Baseline assessments unless all dispensed study drug was returned unused.

Arm/Group Title	FMX103 1.5%	Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.	Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
Measure Participants	494	256
All AEs	98 19.8%	58 22.7%
TEAEs	91 18.4%	54 21.1%
Serious TEAEs (SAEs)	2 0.4%	3 1.2%
Participants with any severe TEAE	1 0.2%	2 0.8%
Treatment-related TEAEs	8 1.6%	7 2.7%
AEs leading to study discontinuation	5 1%	2 0.8%
TEAEs resulting in death	0 0%	1 0.4%

Adverse Events

Time Frame	From Day 0/Baseline until the Safety Follow-up (4 weeks after Week 12 [Final Visit])
Arm/Group Title	FMX103 1.5%		Vehicle Foam
Arm/Group Description	Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed.		Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed.
All Cause Mortality
	FMX103 1.5%		Vehicle Foam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/494 (0%)		1/256 (0.4%)
Serious Adverse Events
	FMX103 1.5%		Vehicle Foam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/494 (0.4%)		3/256 (1.2%)
Cardiac disorders
Myocardial infarction	0/494 (0%)		1/256 (0.4%)
Tachycardia	0/494 (0%)		1/256 (0.4%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/494 (0%)		1/256 (0.4%)
Nausea	1/494 (0.2%)		0/256 (0%)
General disorders
Chest discomfort	1/494 (0.2%)		0/256 (0%)
Chest pain	0/494 (0%)		1/256 (0.4%)
Fatigue	1/494 (0.2%)		0/256 (0%)
Immune system disorders
Seasonal allergy	1/494 (0.2%)		0/256 (0%)
Metabolism and nutrition disorders
Dehydration	1/494 (0.2%)		0/256 (0%)
Nervous system disorders
Syncope	1/494 (0.2%)		0/256 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/494 (0.2%)		0/256 (0%)
Vascular disorders
Hypertension	0/494 (0%)		1/256 (0.4%)
Other (Not Including Serious) Adverse Events
	FMX103 1.5%		Vehicle Foam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/494 (0.8%)		5/256 (2%)
Infections and infestations
Upper respiratory tract infection	4/494 (0.8%)		5/256 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.