A Controlled Study to Assess the Efficacy, Safety and Tolerability of Oral DFD-29 Extended Release Capsules

Study Overview
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Brief Summary
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Clinical assessments of efficacy will be conducted based on Investigator's Global Assessment (IGA, modified scale without erythema), Clinician's Erythema Assessment (CEA), and on inflammatory lesion counts at Weeks 4, 8, 12 and 16 in comparison to Baseline.

Detailed Description
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Two hundred (200) male and female subjects with papulopustular rosacea will be enrolled to get 176 completed subjects (forty-four (44) completers each in groups 1 to 4). After assessing eligibility during an up to 28 days screening period, 200 subjects will be enrolled in the study (fifty subjects each in groups 1 to 4). Subject visits are scheduled at Screening, Baseline (Day 1), and Weeks 4, 8, 12 and 16. Clinical assessments of efficacy will be conducted based on Investigator's Global Assessment (IGA, modified scale without erythema), Clinician's Erythema Assessment (CEA), and on inflammatory lesion counts at Weeks 4, 8, 12 and 16 in comparison to Baseline. Additionally, high sensitivity C-reactive protein (hs-CRP) in the blood will be assessed at Baseline, and at Week 16 to explore any impact of the treatment on the inflammatory pathology.

Official Title
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A Multi-Center, Randomized, Double-Blind, Parallel-Group, Controlled Study to Assess the Efficacy, Safety and Tolerability of Oral DFD-29 Extended Release Capsules for the Treatment of Inflammatory Lesions of Rosacea Over 16 Weeks

Conditions
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Rosacea

Intervention / Treatment
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* Drug: DFD-29 Extended Release Capsules (40 mg)
* Drug: DFD-29 Extended Release Capsules (20 mg)
* Drug: Oraycea® (doxycycline) Capsules
* Drug: Placebo Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be able to understand the requirements of the study and be willing to give written informed consent. Male and female subjects aged 18 years and above. Subjects, any gender or ethnicity (and of Fitzpatrick skin type I - III), must be in good general health as determined by the Investigator. Subjects must have a clinical diagnosis of papulopustular rosacea, IGA grade 2 - 4. Subjects must have 10 - 40 (both inclusive) inflammatory lesions (papules and pustules) of rosacea over the face. Subjects must have not more than 2 nodules. Subjects with moderate to severe erythema with a total score of 5 - 20 on the CEA scale. Females must have a negative urine pregnancy test at the screening and baseline visit. Females must either be postmenopausal with no menses for at least 12 months or surgically sterile (hysterectomy or tubal ligation) or agree to use a highly effective method of contraception with a pearl index of <1% up to 1 month after last dose. Subjects must be in good general health as determined by the investigator and supported by the medical history and normal or not clinically significant abnormal vital signs (blood pressure and pulse). Exclusion Criteria: Females who are pregnant or nursing or planning to become pregnant during the study. Male whose female partner is planning to conceive a child. Subjects who have been treated for rosacea within the 30 days prior to the Baseline Visit (e.g. metronidazole, azelaic acid, doxycycline or brimonidine). Subjects who have been treated with systemic retinoids within 6 months prior to the Baseline visit. Subjects who have participated in a trial involving any investigational product in the 90 days prior to the Baseline Visit. Subjects with any disease or medical condition that would interfere with the study outcome or place the subject at undue risk. Subjects who use or have used systemic steroids within the 30 days prior to the Baseline Visit or any other immunosuppressive medication. Subjects who are on anti-coagulants or those who are likely to require anti-coagulants during the study period. History of drug or alcohol abuse in the last year.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Multi-Center, Randomized, Double-Blind, Parallel-Group, Controlled Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DFD-29 Extended Release Capsules (40 mg)<br>DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks. | Drug: DFD-29 Extended Release Capsules (40 mg)<br>* Oral Treatment<br>|
| Experimental: DFD-29 Extended Release Capsules (20 mg)<br>DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks. | Drug: DFD-29 Extended Release Capsules (20 mg)<br>* Oral Treatment<br>|
| Experimental: Oraycea® (doxycycline) Capsules<br>Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks. | Drug: Oraycea® (doxycycline) Capsules<br>* Oral Treatment<br>|
| Placebo Comparator: Placebo Capsules<br>Placebo Capsules once per day for 16 weeks. | Drug: Placebo Capsules<br>* Oral Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator Global Assessment (IGA) 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe | Proportion of subjects with Investigator Global Assessment (IGA) 'treatment success' - Grade 0 or 1 at the end of study with at least 2 grade reduction from Baseline to Week 16. | 16 weeks | 
| Total Inflammatory Lesion Count Reduction | The total inflammatory lesion count is carried out by visual inspection by the Investigator at every study visit from Screening up to Week 16 (or at early termination). Inflammatory lesions will be recorded on a diagram of a human face, divided in 4 quadrants. | 16 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Change in RosaQoL (Rosacea Quality of Life) Score From Baseline to Week 16 | The RosaQoL assessment is carried out by the Investigator using the validated RosaQoL questionnaire, at every study visit from Screening up to Week 16 (or at early termination). The RosaQol tool has 21 questions related to the impact that Rosacea has on various dimensions influencing quality of life. Each question is graded from 1 (Never) - 5 (All the time), thus leading to a minimum score of 21 (21 x 1) to a maximum score of 105 (21 x 5) per subject at every visit. Higher the score, poorer is the quality of life. This outcome measured the change in the score from Baseline to Week 16. | Median change in the score from Baseline to Week 16 |