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

• Sponsor: Dr. Reddy's Laboratories Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03340961
• Collaborator: (none)
• Enrollment: 205
• Locations: 14
• Arms: 4
• Actual Duration (Months): 17.9
• Patients Per Site: 14.6
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rosacea	Drug: DFD-29 Extended Release Capsules (40 mg); Drug: DFD-29 Extended Release Capsules (20 mg); Drug: Oraycea® (doxycycline) Capsules; Drug: Placebo Capsules	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 205 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A Multi-Center, Randomized, Double-Blind, Parallel-Group, Controlled StudyA Multi-Center, Randomized, Double-Blind, Parallel-Group, Controlled Study
• Masking: Quadruple (Participant, Care Provider, 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: DFD-29 Extended Release Capsules (40 mg) DFD-29 Extended Release Capsules (20 mg) Doxycycline Modified Release Hard Capsules (40 mg) Placebo Capsules
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Oct 1, 2017
• Actual Primary Completion Date: Nov 7, 2018
• Actual Study Completion Date: Mar 31, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 13	Bad Bentheim		Germany
2	Site 07	Berlin		Germany
3	Site 14	Berlin		Germany
4	Site 09	Bochum		Germany
5	Site 05	Buxtehude		Germany
6	Site 15	Darmstadt		Germany
7	Site 03	Dülmen		Germany
8	Site 08	Leipzig		Germany
9	Site 11	Mahlow		Germany
10	Site 06	Münster		Germany
11	Site 10	Osnabrück		Germany
12	Site 01	Pommelsbrunn		Germany
13	Site 04	Potsdam		Germany
14	Site 02	Wuppertal		Germany

Sponsors and Collaborators

• Dr. Reddy's Laboratories Limited

Investigators

• Study Director: Srinivas Sidgiddi, MD, Director-Clinical Development

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 6, 2018
• Study Protocol - Oct 2, 2018

More Information

Publications

None provided.

• Responsible Party: Dr. Reddy's Laboratories Limited
• ClinicalTrials.gov Identifier: NCT03340961
• Other Study ID Numbers: DFD-29-CD-002
• First Posted: Nov 14, 2017
• Last Update Posted: Mar 1, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Rosacea; Doxycycline

Study Results

Participant Flow

Arm/Group Title	DFD-29 Extended Release Capsules (40 mg)	DFD-29 Extended Release Capsules (20 mg)	Oraycea® (Doxycycline) Capsules	Placebo Capsules
Arm/Group Description	DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (40 mg): Oral Treatment	DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (20 mg): Oral Treatment	Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks. Oraycea® (doxycycline) Capsules: Oral Treatment	Placebo Capsules once per day for 16 weeks. Placebo Capsules: Oral Treatment
Period Title: Overall Study
STARTED	53	50	49	53
COMPLETED	47	38	40	35
NOT COMPLETED	6	12	9	18

Baseline Characteristics

Arm/Group Title	DFD-29 Extended Release Capsules (40 mg)	DFD-29 Extended Release Capsules (20 mg)	Oraycea® (Doxycycline) Capsules	Placebo Capsules	Total
Arm/Group Description	DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (40 mg): Oral Treatment	DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (20 mg): Oral Treatment	Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks. Oraycea® (doxycycline) Capsules: Oral Treatment	Placebo Capsules once per day for 16 weeks. Placebo Capsules: Oral Treatment	Total of all reporting groups
Overall Participants	53	50	49	53	205
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	45 84.9%	40 80%	40 81.6%	42 79.2%	167 81.5%
>=65 years	8 15.1%	10 20%	9 18.4%	11 20.8%	38 18.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.8 (15.05)	51.1 (13.13)	51.6 (12.94)	52.5 (12.92)	50.5 (13.64)
Sex: Female, Male (Count of Participants)
Female	34 64.2%	34 68%	29 59.2%	27 50.9%	124 60.5%
Male	19 35.8%	16 32%	20 40.8%	26 49.1%	81 39.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	53 100%	50 100%	49 100%	53 100%	205 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Germany	53 100%	50 100%	49 100%	53 100%	205 100%
Total Inflammatory Lesion Count (Number of lesions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Number of lesions]	23.8 (8.69)	24.5 (9.49)	23.8 (7.56)	24.0 (8.40)	24.0 (8.51)

Outcome Measures

1. Primary Outcome

Title	Investigator Global Assessment (IGA) 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe
Description	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

Outcome Measure Data

Analysis Population Description

The FAS (full analysis set) included all subjects that had at least one post Baseline efficacy assessment.

Arm/Group Title	DFD-29 Extended Release Capsules (40 mg)	DFD-29 Extended Release Capsules (20 mg)	Oraycea® (Doxycycline) Capsules	Placebo Capsules
Arm/Group Description	DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (40 mg): Oral Treatment	DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (20 mg): Oral Treatment	Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks. Oraycea® (doxycycline) Capsules: Oral Treatment	Placebo Capsules once per day for 16 weeks. Placebo Capsules: Oral Treatment
Measure Participants	53	47	48	52
Count of Participants [Participants]	35 66%	15 30%	16 32.7%	6 11.3%

2. Primary Outcome

Title	Total Inflammatory Lesion Count Reduction
Description	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

Outcome Measure Data

Analysis Population Description

FAS population

Arm/Group Title	DFD-29 Extended Release Capsules (40 mg)	DFD-29 Extended Release Capsules (20 mg)	Oraycea® (Doxycycline) Capsules	Placebo Capsules
Arm/Group Description	DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (40 mg): Oral Treatment	DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (20 mg): Oral Treatment	Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks. Oraycea® (doxycycline) Capsules: Oral Treatment	Placebo Capsules once per day for 16 weeks. Placebo Capsules: Oral Treatment
Measure Participants	53	47	48	52
Mean (Standard Deviation) [Count of lesions]	-19.2 (9.72)	-12.6 (12.92)	-10.5 (15.18)	-7.3 (10.12)

3. Secondary Outcome

Title	Median Change in RosaQoL (Rosacea Quality of Life) Score From Baseline to Week 16
Description	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

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	DFD-29 Extended Release Capsules (40 mg)	DFD-29 Extended Release Capsules (20 mg)	Oraycea® (Doxycycline) Capsules	Placebo Capsules
Arm/Group Description	DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (40 mg): Oral Treatment	DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (20 mg): Oral Treatment	Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks. Oraycea® (doxycycline) Capsules: Oral Treatment	Placebo Capsules once per day for 16 weeks. Placebo Capsules: Oral Treatment
Measure Participants	53	47	48	52
Median (Full Range) [score on a scale]	-11.0	-8.0	-3.0	-1.0

Adverse Events

Time Frame	AEs were collected from subjects from the time of signing of the ICF up to Week 16/End of Study Visit.
Adverse Event Reporting Description	Adverse events were collected by spontaneous reports from subjects, either verbal or recorded in the subject's diary, by directed question of subjects, and by observation. All AEs from the time of signing of the ICF up to the EOS visit were recorded. AEs occurring from the time of first study drug administration up to the End-of-Study were defined as treatment emergent AEs.
Arm/Group Title	DFD-29 Extended Release Capsules (40 mg)		DFD-29 Extended Release Capsules (20 mg)		Oraycea® (Doxycycline) Capsules		Placebo Capsules
Arm/Group Description	DFD-29 (minocycline HCl) Extended Release Capsules (40 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (40 mg): Oral Treatment		DFD-29 (minocycline HCl) Extended Release Capsules (20 mg) once per day for 16 weeks. DFD-29 Extended Release Capsules (20 mg): Oral Treatment		Oraycea® (doxycycline) Modified Release Hard Capsules (40 mg) once per day for 16 weeks. Oraycea® (doxycycline) Capsules: Oral Treatment		Placebo Capsules once per day for 16 weeks. Placebo Capsules: Oral Treatment
All Cause Mortality
	DFD-29 Extended Release Capsules (40 mg)		DFD-29 Extended Release Capsules (20 mg)		Oraycea® (Doxycycline) Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/48 (0%)		0/48 (0%)		0/53 (0%)
Serious Adverse Events
	DFD-29 Extended Release Capsules (40 mg)		DFD-29 Extended Release Capsules (20 mg)		Oraycea® (Doxycycline) Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/52 (1.9%)		2/48 (4.2%)		2/48 (4.2%)		0/53 (0%)
Cardiac disorders
Coronary artery disease	1/52 (1.9%)	1	0/48 (0%)	0	0/48 (0%)	0	0/53 (0%)	0
Atrial fibrillation	0/52 (0%)	0	1/48 (2.1%)	1	0/48 (0%)	0	0/53 (0%)	0
Eye disorders
Retinal detachment	0/52 (0%)	0	1/48 (2.1%)	1	0/48 (0%)	0	0/53 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma	0/52 (0%)	0	0/48 (0%)	0	1/48 (2.1%)	1	0/53 (0%)	0
Nervous system disorders
Papilloma	0/52 (0%)	0	0/48 (0%)	0	1/48 (2.1%)	1	0/53 (0%)	0
Other (Not Including Serious) Adverse Events
	DFD-29 Extended Release Capsules (40 mg)		DFD-29 Extended Release Capsules (20 mg)		Oraycea® (Doxycycline) Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/52 (71.2%)		33/48 (68.8%)		27/48 (56.3%)		35/53 (66%)
Gastrointestinal disorders
Abdominal Pain Upper	0/52 (0%)	0	3/48 (6.3%)	3	3/48 (6.3%)	9	3/53 (5.7%)	3
Diarrhoea	4/52 (7.7%)	5	4/48 (8.3%)	4	0/48 (0%)	0	3/53 (5.7%)	7
Investigations
Nasopharyngitis	11/52 (21.2%)	11	8/48 (16.7%)	11	7/48 (14.6%)	7	6/35 (17.1%)	8
Musculoskeletal and connective tissue disorders
Back Pain	0/52 (0%)	0	4/48 (8.3%)	4	4/48 (8.3%)	6	6/53 (11.3%)	6
Nervous system disorders
Headache	22/52 (42.3%)	47	14/48 (29.2%)	35	13/48 (27.1%)	37	13/53 (24.5%)	29
Skin and subcutaneous tissue disorders
Rosacea	0/52 (0%)	0	0/48 (0%)	0	0/48 (0%)	0	4/53 (7.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.