A Study to Evaluate the Long-Term Safety of Topical Administration of FMX103 in the Treatment of Moderate to Severe Papulopustular Rosacea

This is 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. Subjects entering this study will have recently participated in 1 of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy studies (FX2016-11 and FX2016-12 - NCT03142451). Subjects must demonstrate that they are eligible to continue into Study FX2016-13 based on safety evaluations and IGA score performed at Final Visit of one of the previous double-blind studies.

At the completion of the Final Visit in Study FX2016-11 or Study FX2016-12, subjects may be invited to continue into this open-label study for an additional 40 weeks of open-label treatment. A minimum of 400 subjects will be enrolled into from Studies FX2016-11 and FX2016-12. Subjects who elect to continue into this open-label study will receive supplies of active FMX103 1.5% minocycline foam.

• FMX103 1.5% (Drug): FMX103 1.5% minocycline foam

Primary outcomes

• Absolute Change From Baseline in Inflammatory Lesion Count at Week 40 [Day 0/ Baseline (Final visit of previous DB study [Week 12]) and at Week 40]: Change from Baseline (Baseline visit in the initial DB study \[FX2016-11 or FX2016-12\] and Baseline visit of the open-label extension study \[Week 12\]) in inflammatory lesion count at Week 40 is reported. The lesion counts performed at Week 12 \[Final Visit\] in Study FX2016-11 or Study FX2016-12 constituted as the Baseline value for this study. Changes from Baseline were calculated as the Baseline \[pre-dose\] value minus the post-Baseline value, so that decreases reflected a reduction in lesion count. The number of papules, pustules, and nodules were counted, and the numbers recorded.
• Percentage of Participants Achieving Investigator's Global Assessments (IGA) Treatment Success at Week 40 [At Week 40]: The IGA scale for Rosacea, was used by the Investigators to assess the severity of a participant's Rosacea. 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 (score of clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Baseline.

Secondary outcomes

• Absolute Change From Baseline in Inflammatory Lesion Count at Weeks 4, 10, 16, 22, 28, and 34 [Day 0/ Baseline (Final visit of previous DB study [Week 12]) and at Weeks 4, 10, 16, 22, 28, and 34]: Change from Baseline (Baseline visit in the initial DB study \[FX2016-11 or FX2016-12\] and Baseline visit of the open-label extension study \[Week 12\]) in inflammatory lesion count at Week 40 is reported. The lesion counts performed at Week 12 \[Final Visit\] in Study FX2016-11 or Study FX2016-12 constituted as the Baseline value for this study. Changes from Baseline were calculated as the Baseline \[pre-dose\] value minus the post-Baseline value, so that decreases reflected a reduction in lesion count. The number of papules, pustules, and nodules were counted, and the numbers recorded.
• Percentage of Participants Achieving IGA Treatment Success at Weeks 4, 10, 16, 22, 28 and 34 [At Weeks 4, 10, 16, 22, 28 and Week 34]: The IGA scale for Rosacea, was used by the Investigators to assess the severity of a participant's Rosacea. 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 (score of clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Baseline.
• Percentage Change From Baseline in Inflammatory Lesion Count at Weeks 4, 10, 16, 22, 28, and 34 [Day 0/ Baseline (Final visit of previous DB study [Week 12]) and at Weeks 4, 10, 16, 22, 28, and 34]: Change from Baseline (Baseline visit in the initial DB study \[FX2016-11 or FX2016-12\] and Baseline visit of the open-label extension study \[Week 12\]) in inflammatory lesion count at Week 40 is reported. The lesion counts performed at Week 12 \[Final Visit\] in Study FX2016-11 or Study FX2016-12 constituted as the Baseline value for this study. Changes from Baseline were calculated as the Baseline \[pre-dose\] value minus the post-Baseline value, so that decreases reflected a reduction in lesion count. The number of papules, pustules, and nodules were counted, and the numbers recorded.
• Number of Participants Reporting Satisfaction and Dissatisfaction With the Study Drug Based on Subject Satisfaction Questionnaire (SSQ) at Week 40 [At Week 40]: The questionnaire consisted of questions with responses on scale with scores: as 1 (Very satisfied or Very likely ) to 5 (Very dissatisfied or Very unlikely) for each variable as for example, Easy to use, 1 is very satisfied and 5 is very dissatisfied. The minimum score represented best outcome and higher score represented worst outcome.
• Number of Participants With Adverse Events (AEs) [Day 0/ Baseline (Final visit of previous DB study [Week 12]) until safety follow-up (Week 44)]: Evaluation of the long-term safety of topical FMX103 1.5% minocycline foam in the treatment of moderate to severe facial papulopustular rosacea for 40 weeks. A Treatment-emergent Adverse Events (TEAEs) was defined as any AE with an onset date after the first dose date of the open-label extension study and before the last application of study drug plus 3 days having been absent pre-treatment or worsened relative to the pre-treatment state.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Have completed 12 weeks of treatment in either Study FX2016-11 or Study FX2016-12.
2. Have not had a worsening of disease, determined by the Investigator's Global Assessment (IGA), at Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment in Study FX2016-11 or Study FX2016-12.

Exclusion Criteria:

1. Have a new systemic disease or condition, including an ongoing AE that might interfere with the conduct of the study or the interpretation of results.
2. Have developed a condition that would have been exclusionary for Study FX2016-11 or Study FX2016-12, including pseudomembranous colitis, antibiotic associated colitis, hepatitis, liver damage, renal impairment, drug addiction, or alcohol abuse.

Participant flow

Outcome results

• Absolute Change From Baseline in Inflammatory Lesion Count at Week 40 (Primary), Mean, Lesions: DB-FMX103 1.5% Minocycline Foam 23.0 +/- 10.96; DB-Vehicle Foam 22.5 +/- 10.83
• Percentage of Participants Achieving Investigator's Global Assessments (IGA) Treatment Success at Week 40 (Primary), Number, Percentage of participants: DB-FMX103 1.5% Minocycline Foam 81.6; DB-Vehicle Foam 76.0
• Absolute Change From Baseline in Inflammatory Lesion Count at Weeks 4, 10, 16, 22, 28, and 34 (Secondary), Mean, Lesions: DB-FMX103 1.5% Minocycline Foam 19.5 +/- 11.57; DB-Vehicle Foam 17.4 +/- 12.18
• Percentage of Participants Achieving IGA Treatment Success at Weeks 4, 10, 16, 22, 28 and 34 (Secondary), Number, Percentage of participants: DB-FMX103 1.5% Minocycline Foam 50.6; DB-Vehicle Foam 48.2
• Percentage Change From Baseline in Inflammatory Lesion Count at Weeks 4, 10, 16, 22, 28, and 34 (Secondary), Mean, Percent Change: DB-FMX103 1.5% Minocycline Foam 67.91 +/- 27.569; DB-Vehicle Foam 61.25 +/- 32.306
• Number of Participants Reporting Satisfaction and Dissatisfaction With the Study Drug Based on Subject Satisfaction Questionnaire (SSQ) at Week 40 (Secondary), Number, Participants: DB-FMX103 1.5% Minocycline Foam 178; DB-Vehicle Foam 82
• Number of Participants With Adverse Events (AEs) (Secondary), Count of participants, Participants: DB-FMX103 1.5% Minocycline Foam 151; DB-Vehicle Foam 70

Adverse events

Time frame: Day 0/ Baseline (Final visit of previous DB study [Week 12]) until safety follow-up (Week 44)

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2017-06-22)
• Statistical Analysis Plan (PDF, 2019-01-08)