A Study to Assess the Efficacy, Safety and Tolerability of DFD-04

• Sponsor: Dr. Reddy's Laboratories Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02828241
• Collaborator: (none)
• Enrollment: 61
• Locations: 8
• Arms: 2
• Actual Duration (Months): 16
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this exploratory study is to assess the efficacy, safety and tolerability of DFD-04 Ointment for topical treatment of rosacea over 12 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Rosacea	Drug: DFD-04 Ointment; Other: Placebo Ointment	Phase 2

Detailed Description

Subjects with mild to moderate papulopustular rosacea (Investigator's Global Assessment [IGA] grade 2-3), a Clinician's Erythema Assessment (CEA) score of 2-3 and 6-30 inflammatory lesions (papules and pustules) were randomized to treatment with DFD-04 ointment or Vehicle ointment in a ratio of 2:1.

During the 12-week treatment period subjects used the IMP twice daily with approximately 12 hours between applications. Subjects were instructed to treat affected skin in a defined treatment area on the face.

The investigator assessed efficacy by using an IGA 5-point scale and CEA 4-point scale and by counting the number of inflammatory lesions on the face at Baseline (Day 1) and Weeks 4, 8 and 12 (End of Treatment [EoT], defined as complete clearance of inflammatory lesions or Week 12, whichever was earlier). Furthermore, a non-invasive biomarker assessment was done by using a Transdermal Analysis Patch (TAP) at Baseline (Day 1) and Weeks 4 and 12.

Safety assessments included investigator's assessment of application site reactions at Baseline (Day 1) and Weeks 4, 8, and 12 for all treated areas.

Other safety assessments included vital signs (blood pressure [BP] and pulse rate) and urine pregnancy tests (UPTs) (only for females), clinical laboratory parameters (serum and urine), extent of exposure, and Adverse Events.

In addition, pharmacokinetic (PK) analysis was performed to evaluate the systemic exposures of itraconazole and its active metabolite, hydroxyl-itraconazole, with blood samples drawn from the first 12 subjects at various pre-specified timepoints.

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-Blind, Parallel-group, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of DFD-04 (Itraconazole) Ointment, 5% in Patients With Inflammatory Lesions of Rosacea Over 12 Weeks
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DFD-04 Ointment DFD-04 (Itraconazole) Ointment	Drug: DFD-04 Ointment
Placebo Comparator: Placebo Ointment Placebo Ointment	Other: Placebo Ointment; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Change in Inflammatory Lesion Counts [At the end of study (12 weeks)]

   Mean change from Baseline in the inflammatory lesion count at the End of Treatment. A lower score at the end of the study compared to Baseline is considered a better outcome.

2. Number of Subjects With Investigator's Global Assessment (IGA) Success [At the end of study (12 weeks)]

   Number of subjects with treatment success based on Investigator's Global Assessment (IGA) score at the End of Treatment, defined as an IGA score of 0 (clear) or 1 (almost clear) with composite grade change from Baseline of at least 2 points.

3. Number of Subjects With Treatment Success by Clinician's Erythema Assessment (CEA) Scale [At end of study (12 weeks)]

   Number of subjects with Treatment Success defined as a score of 0 or 1 and a 2 grade improvement on the CEA scale from Baseline to 12 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• 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. Subjects must be willing to provide authorization to use protected health information.

3. Subjects, any gender or race, must be in good general health as determined by the Investigator

4. Subjects must have a clinical diagnosis of papulopustular rosacea, Investigator's Global Assessment (IGA) grade 2 - 3.

5. Subjects must have 6 - 30 inflammatory lesions (papules and pustules) of rosacea over the face.

6. Subjects must have a Clinician's Erythema Assessment (CEA) score of 2 - 3.

7. Subjects must have no more than 2 nodules.

8. Subjects must agree to only use the study products and to not use any other treatment for rosacea (prescription or over the counter) or any other skin care or cosmetics product (make-up etc.) on the facial skin of the treatment area during the course of the study.

9. Subjects must be free of any systemic or dermatologic disorder, which in the opinion of the Investigator, will interfere with the study results.

10. Females have a negative urine pregnancy test at the Screening and Baseline Visit.

11. 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 reliable method of contraception with a failure rate of less than 1 percent per year when used consistently and correctly.

12. Subject 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).

13. Subject is physically able to apply study product to all affected areas.

Exclusion Criteria:

1. Females who are pregnant or nursing or planning to become pregnant during the study.

2. Subjects who have been treated for rosacea within the 30 days prior to the Baseline Visit.

3. Subjects who have been treated with systemic retinoids within 6 months prior to the Baseline visit.

4. Subjects who have participated in a trial involving any investigational product in the 30 days prior to the Baseline Visit.

5. Subjects with any disease or medical condition that would interfere with the study or place the subject at undue risk especially cardiovascular diseases, reduced lung function (including asthma), renal dysfunction or liver dysfunction.

6. Subjects who have been treated within 30 days prior to baseline visit with methadone,disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin, ticagrelor, terfenadine, astemizole, mizolastine, eletriptan, as well as lovastatin, simvastatin and atorvastatin and, in subjects with varying degrees of renal or hepatic impairment, colchicine, fesoterodine, telithromycin and solifenacin.

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 positive for human immunodeficiency virus (HIV), hepatitis B and hepatitis C-test at screening.

9. Subjects who are unable to comply with study requirements.

10. Subjects with other skin diseases that may confound the evaluation of rosacea.

11. History of organ transplant requiring immunosuppression, HIV, or other immune compromised state.

12. Subject who in the opinion of the investigator or physician performing the initial examination the subject should not participate in the trial, e.g. due to probable noncompliance or inability to understand the trial and give adequately informed consent

13. Subject with close affiliation with the investigator (e.g. a close relative) or persons working at the respective trial sites or subject who are an employee of sponsor.

14. Subject institutionalized because of legal or regulatory order.

15. History of drug or alcohol abuse in the last year.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 201	Berlin		Germany	10117
2	Site 208	Berlin		Germany	10783
3	Site 202	Bochum		Germany	44803
4	Site 205	Hamburg		Germany	22391
5	Site 203	Mahlow		Germany	15831
6	Site 204	Munster		Germany	48179
7	Site 207	Potsdam		Germany	14467
8	Site 206	Wiesbaden		Germany	65199

Sponsors and Collaborators

• Dr. Reddy's Laboratories Limited

Investigators

• Study Director: Srinivas R Sidgiddi, MD, Dr. Reddy's Laboratories Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Reddy's Laboratories Limited
• ClinicalTrials.gov Identifier: NCT02828241
• Other Study ID Numbers: DFD04-CD-002
• First Posted: Jul 11, 2016
• Last Update Posted: Jan 23, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Rosacea

Study Results

Participant Flow

Recruitment Details	Subjects were randomized to either DFD-04 Ointment or Placebo Ointment in a ratio of 2:1

Arm/Group Title	DFD-04 Ointment	Placebo Ointment
Arm/Group Description	DFD-04 (Itraconazole) Ointment applied over the affected areas on the face twice daily with approximately 12 hours between applications.	Placebo Ointment applied over the affected areas on the face twice daily with approximately 12 hours between applications.
Period Title: Overall Study
STARTED	38	23
COMPLETED	30	21
NOT COMPLETED	8	2

Baseline Characteristics

Arm/Group Title	DFD-04 Ointment	Placebo Ointment	Total
Arm/Group Description	DFD-04 (Itraconazole) Ointment	Placebo Ointment t	Total of all reporting groups
Overall Participants	38	23	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.4 (8.1)	44.3 (10.2)	48.1 (9.4)
Sex: Female, Male (Count of Participants)
Female	25 65.8%	18 78.3%	43 70.5%
Male	13 34.2%	5 21.7%	18 29.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	38 100%	23 100%	61 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Germany	38 100%	23 100%	61 100%

Outcome Measures

1. Primary Outcome

Title	Change in Inflammatory Lesion Counts
Description	Mean change from Baseline in the inflammatory lesion count at the End of Treatment. A lower score at the end of the study compared to Baseline is considered a better outcome.
Time Frame	At the end of study (12 weeks)

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT)

Arm/Group Title	DFD-04 Ointment	Placebo Ointment
Arm/Group Description	DFD-04 (Itraconazole) Ointment	Placebo Ointment t
Measure Participants	38	23
Mean (Standard Deviation) [Number of lesions]	-1.4 (13.8)	2.9 (17.5)

2. Primary Outcome

Title	Number of Subjects With Investigator's Global Assessment (IGA) Success
Description	Number of subjects with treatment success based on Investigator's Global Assessment (IGA) score at the End of Treatment, defined as an IGA score of 0 (clear) or 1 (almost clear) with composite grade change from Baseline of at least 2 points.
Time Frame	At the end of study (12 weeks)

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population

Arm/Group Title	DFD-04 Ointment	Placebo Ointment
Arm/Group Description	DFD-04 (Itraconazole) Ointment	Placebo Ointment
Measure Participants	38	23
Number [participants]	3 7.9%	2 8.7%

3. Primary Outcome

Title	Number of Subjects With Treatment Success by Clinician's Erythema Assessment (CEA) Scale
Description	Number of subjects with Treatment Success defined as a score of 0 or 1 and a 2 grade improvement on the CEA scale from Baseline to 12 weeks.
Time Frame	At end of study (12 weeks)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	DFD-04 Ointment	Placebo Ointment
Arm/Group Description	DFD-04 (Itraconazole) Ointment	Placebo Ointment t
Measure Participants	38	23
Number [participants]	2 5.3%	2 8.7%

Adverse Events

Time Frame	From start of treatment until the end of study visit at 12 weeks.
Arm/Group Title	DFD-04 Ointment		Placebo Ointment
Arm/Group Description	DFD-04 (Itraconazole) Ointment		Placebo Ointment t
All Cause Mortality
	DFD-04 Ointment		Placebo Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/23 (0%)
Serious Adverse Events
	DFD-04 Ointment		Placebo Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	DFD-04 Ointment		Placebo Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/38 (97.4%)		19/23 (82.6%)
Gastrointestinal disorders
Any Gastrointestinal Disorder	4/38 (10.5%)	7	3/23 (13%)	6
Toothache	2/38 (5.3%)	4	0/23 (0%)	0
General disorders
Any General Disorder and Administrative Site Condition	29/38 (76.3%)	127	13/23 (56.5%)	36
Application Site Dryness	7/38 (18.4%)	7	2/23 (8.7%)	2
Application Site Erythema	10/38 (26.3%)	13	4/23 (17.4%)	4
Application Site Exfoliation	5/38 (13.2%)	5	4/23 (17.4%)	4
Application Site Pain	22/38 (57.9%)	46	7/23 (30.4%)	13
Application Site Pruritus	21/38 (55.3%)	42	9/23 (39.1%)	9
Application Site Reaction	6/38 (15.8%)	6	1/23 (4.3%)	1
Infections and infestations
Any Infections and Infestations	12/38 (31.6%)	16	7/23 (30.4%)	11
Application Site Pustules	2/38 (5.3%)	2	0/23 (0%)	0
Bronchitis Bacterial	1/38 (2.6%)	1	2/23 (8.7%)	2
Nasopharyngitis	6/38 (15.8%)	7	5/23 (21.7%)	6
Investigations
Any Investigations	2/38 (5.3%)	5	1/23 (4.3%)	1
Musculoskeletal and connective tissue disorders
Any Musculoskeletal and Connective Tissue Disorders	2/38 (5.3%)	2	0/23 (0%)	0
Nervous system disorders
Headache	6/38 (15.8%)	9	2/23 (8.7%)	2
Skin and subcutaneous tissue disorders
Any Skin and Subcutaneous Tissue Disorders	7/38 (18.4%)	13	5/23 (21.7%)	6
Erythema	3/38 (7.9%)	3	2/23 (8.7%)	3
Pruritus	2/38 (5.3%)	2	0/23 (0%)	0
Rosacea	0/38 (0%)	0	2/23 (8.7%)	2
Skin Burning Sensation	2/38 (5.3%)	3	0/23 (0%)	0
Skin Reaction	2/38 (5.3%)	2	0/23 (0%)	0

Limitations/Caveats

Phase 2 pilot study so sample size was small.

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.