Rosacea
Conditions
Brief summary
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
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.
Interventions
DRUGDFD-29 Extended Release Capsules (40 mg)
Oral Treatment
DRUGDFD-29 Extended Release Capsules (20 mg)
Oral Treatment
DRUGOraycea® (doxycycline) Capsules
Oral Treatment
DRUGPlacebo Capsules
Oral Treatment
Sponsors
Dr. Reddy's Laboratories Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Each subject will be allocated to one of the following treatment groups, receiving 1 capsule once daily in the morning for 16 weeks: 1. DFD-29 Extended Release Capsules (40 mg) 2. DFD-29 Extended Release Capsules (20 mg) 3. Doxycycline Modified Release Hard Capsules (40 mg) 4. Placebo Capsules
Intervention model description
A Multi-Center, Randomized, Double-Blind, Parallel-Group, Controlled Study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must be able to understand the requirements of the study and be willing to give written informed consent. 2. Male and female subjects aged 18 years and above. 3. Subjects, any gender or ethnicity (and of Fitzpatrick skin type I - III), must be in good general health as determined by the Investigator. 4. Subjects must have a clinical diagnosis of papulopustular rosacea, IGA grade 2 - 4. 5. Subjects must have 10 - 40 (both inclusive) inflammatory lesions (papules and pustules) of rosacea over the face. 6. Subjects must have not more than 2 nodules. 7. Subjects with moderate to severe erythema with a total score of 5 - 20 on the CEA scale. 8. Females must have a negative urine pregnancy test at the screening and baseline visit. 9. 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. 10. 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
1. Females who are pregnant or nursing or planning to become pregnant during the study. 2. Male whose female partner is planning to conceive a child. 3. Subjects who have been treated for rosacea within the 30 days prior to the Baseline Visit (e.g. metronidazole, azelaic acid, doxycycline or brimonidine). 4. Subjects who have been treated with systemic retinoids within 6 months prior to the Baseline visit. 5. Subjects who have participated in a trial involving any investigational product in the 90 days prior to the Baseline Visit. 6. Subjects with any disease or medical condition that would interfere with the study outcome or place the subject at undue risk. 7. Subjects who use or have used systemic steroids within the 30 days prior to the Baseline Visit or any other immunosuppressive medication. 8. Subjects who are on anti-coagulants or those who are likely to require anti-coagulants during the study period. 9. History of drug or alcohol abuse in the last year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Global Assessment (IGA) 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe | 16 weeks | 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. |
| Total Inflammatory Lesion Count Reduction | 16 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Change in RosaQoL (Rosacea Quality of Life) Score From Baseline to Week 16 | Median change in the 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. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DFD-29 Extended Release Capsules (40 mg) DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks.
DFD-29 Extended Release Capsules (40 mg): Oral Treatment | 53 |
| DFD-29 Extended Release Capsules (20 mg) DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks.
DFD-29 Extended Release Capsules (20 mg): Oral Treatment | 50 |
| Oraycea® (Doxycycline) Capsules Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks.
Oraycea® (doxycycline) Capsules: Oral Treatment | 49 |
| Placebo Capsules Placebo Capsules once per day for 16 weeks.
Placebo Capsules: Oral Treatment | 53 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 2 | 4 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 0 |
| Overall Study | Subject developed an exclusion criterion | 0 | 1 | 0 | 0 |
| Overall Study | Use of prohibited treatment | 0 | 3 | 2 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 4 | 7 |
| Overall Study | Wrongful enrollment (I/E criteria not me | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | DFD-29 Extended Release Capsules (40 mg) | DFD-29 Extended Release Capsules (20 mg) | Oraycea® (Doxycycline) Capsules | Placebo Capsules | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 10 Participants | 9 Participants | 11 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 40 Participants | 40 Participants | 42 Participants | 167 Participants |
| Age, Continuous | 46.8 years STANDARD_DEVIATION 15.05 | 51.1 years STANDARD_DEVIATION 13.13 | 51.6 years STANDARD_DEVIATION 12.94 | 52.5 years STANDARD_DEVIATION 12.92 | 50.5 years STANDARD_DEVIATION 13.64 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 53 Participants | 50 Participants | 49 Participants | 53 Participants | 205 Participants |
| Region of Enrollment Germany | 53 participants | 50 participants | 49 participants | 53 participants | 205 participants |
| Sex: Female, Male Female | 34 Participants | 34 Participants | 29 Participants | 27 Participants | 124 Participants |
| Sex: Female, Male Male | 19 Participants | 16 Participants | 20 Participants | 26 Participants | 81 Participants |
| Total Inflammatory Lesion Count | 23.8 Number of lesions STANDARD_DEVIATION 8.69 | 24.5 Number of lesions STANDARD_DEVIATION 9.49 | 23.8 Number of lesions STANDARD_DEVIATION 7.56 | 24.0 Number of lesions STANDARD_DEVIATION 8.4 | 24.0 Number of lesions STANDARD_DEVIATION 8.51 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 48 | 0 / 48 | 0 / 53 |
| other Total, other adverse events | 37 / 52 | 33 / 48 | 27 / 48 | 35 / 53 |
| serious Total, serious adverse events | 1 / 52 | 2 / 48 | 2 / 48 | 0 / 53 |
Outcome results
Primary
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.
Time frame: 16 weeks
Population: The FAS (full analysis set) included all subjects that had at least one post Baseline efficacy assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DFD-29 Extended Release Capsules (40 mg) | Investigator Global Assessment (IGA) 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe | 35 Participants |
| DFD-29 Extended Release Capsules (20 mg) | Investigator Global Assessment (IGA) 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe | 15 Participants |
| Oraycea® (Doxycycline) Capsules | Investigator Global Assessment (IGA) 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe | 16 Participants |
| Placebo Capsules | Investigator Global Assessment (IGA) 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe | 6 Participants |
Primary
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.
Time frame: 16 Weeks
Population: FAS population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DFD-29 Extended Release Capsules (40 mg) | Total Inflammatory Lesion Count Reduction | -19.2 Count of lesions | Standard Deviation 9.72 |
| DFD-29 Extended Release Capsules (20 mg) | Total Inflammatory Lesion Count Reduction | -12.6 Count of lesions | Standard Deviation 12.92 |
| Oraycea® (Doxycycline) Capsules | Total Inflammatory Lesion Count Reduction | -10.5 Count of lesions | Standard Deviation 15.18 |
| Placebo Capsules | Total Inflammatory Lesion Count Reduction | -7.3 Count of lesions | Standard Deviation 10.12 |
Secondary
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.
Time frame: Median change in the score from Baseline to Week 16
Population: FAS Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DFD-29 Extended Release Capsules (40 mg) | Median Change in RosaQoL (Rosacea Quality of Life) Score From Baseline to Week 16 | -11.0 score on a scale |
| DFD-29 Extended Release Capsules (20 mg) | Median Change in RosaQoL (Rosacea Quality of Life) Score From Baseline to Week 16 | -8.0 score on a scale |
| Oraycea® (Doxycycline) Capsules | Median Change in RosaQoL (Rosacea Quality of Life) Score From Baseline to Week 16 | -3.0 score on a scale |
| Placebo Capsules | Median Change in RosaQoL (Rosacea Quality of Life) Score From Baseline to Week 16 | -1.0 score on a scale |