Clinical Trial Results:
Efficacy Comparison of Ivermectin 1% Topical Cream Associated with Doxycycline 40 mg Modified release (MR) Capsules Versus Ivermectin 1% Topical Cream Associated with Placebo in the Treatment of Severe Rosacea
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Summary
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EudraCT number |
2017-000157-40 |
Trial protocol |
HU DE CZ PL |
Global end of trial date |
08 Feb 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Mar 2021
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First version publication date |
11 Mar 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RD.03.SPR.113322
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03075891 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GALDERMA R&D SNC
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Sponsor organisation address |
Les Templiers, 2400 Route des Colles, Biot, France, 06410
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Public contact |
CTA Coordinator, GALDERMA R&D SNC, +33 (0)493 95 70 85, cta.coordinator@galderma.com
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Scientific contact |
CTA Coordinator, GALDERMA R&D SNC, +33 (0)493 95 70 85, cta.coordinator@galderma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Feb 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Feb 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study was to evaluate the efficacy of Ivermectin 1% topical cream associated with Doxycycline 40 mg Modified release (DMR) capsules versus IVM monotherapy in the treatment of severe rosacea.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles from the Declaration of Helsinki revised version (Somerset West, 1996), the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) and in compliance with local regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Jul 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 57
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Country: Number of subjects enrolled |
Czech Republic: 44
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Country: Number of subjects enrolled |
Hungary: 60
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Country: Number of subjects enrolled |
Denmark: 41
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Country: Number of subjects enrolled |
Canada: 17
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Country: Number of subjects enrolled |
United States: 54
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Worldwide total number of subjects |
273
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EEA total number of subjects |
202
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
219
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From 65 to 84 years |
54
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted at 39 sites in Canada, Czech Republic, Germany, Hungary, Poland, and United States of America between 05 July 2017 to 08 February 2018. | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 273 subjects were randomized and treated, out of which 251 subjects completed the study. | |||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind [1] | |||||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Assessor | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Ivermectin 1% Cream + Doxycycline 40 mg MR Capsules | |||||||||||||||||||||||||||||||||
Arm description |
Ivermectin 1 percent (%) cream: Topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Doxycycline 40 milligram (mg) Modified Release (MR) (30 mg Immediate Release & 10 mg Delayed Release beads) capsules: 1 capsule once-daily for 12 weeks. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ivermectin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream
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Routes of administration |
Topical use
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Dosage and administration details |
Subjects applied ivermectin 1% cream topically once a day for 12 weeks.
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Investigational medicinal product name |
Doxycycline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received doxycycline 40 mg MR (30 mg immediate release & 10 mg delayed release beads) capsule orally once-daily for 12 weeks.
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Arm title
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Ivermectin 1% Cream + Oral Placebo Capsules | |||||||||||||||||||||||||||||||||
Arm description |
Ivermectin 1% cream: topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Oral placebo capsules: 1 capsule once-daily for 12 weeks. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ivermectin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream
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Routes of administration |
Topical use
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Dosage and administration details |
Subjects applied ivermectin 1% cream topically once a day for 12 weeks.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received placebo capsule matching to doxycycline 40 mg MR orally once-daily for 12 weeks.
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| Notes [1] - The roles blinded appear to be inconsistent with a double blind trial. Justification: This study was designed as investigator-blinded. |
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Baseline characteristics reporting groups
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Reporting group title |
Ivermectin 1% Cream + Doxycycline 40 mg MR Capsules
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Reporting group description |
Ivermectin 1 percent (%) cream: Topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Doxycycline 40 milligram (mg) Modified Release (MR) (30 mg Immediate Release & 10 mg Delayed Release beads) capsules: 1 capsule once-daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ivermectin 1% Cream + Oral Placebo Capsules
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Reporting group description |
Ivermectin 1% cream: topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Oral placebo capsules: 1 capsule once-daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ivermectin 1% Cream + Doxycycline 40 mg MR Capsules
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Reporting group description |
Ivermectin 1 percent (%) cream: Topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Doxycycline 40 milligram (mg) Modified Release (MR) (30 mg Immediate Release & 10 mg Delayed Release beads) capsules: 1 capsule once-daily for 12 weeks. | ||
Reporting group title |
Ivermectin 1% Cream + Oral Placebo Capsules
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Reporting group description |
Ivermectin 1% cream: topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Oral placebo capsules: 1 capsule once-daily for 12 weeks. | ||
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End point title |
Percent Change From Baseline in Inflammatory Lesion Count at Week 12 | ||||||||||||
End point description |
Percent change from baseline in inflammatory lesion count at week 12 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (that is [i.e.] papules and pustules) which were defined as follows: Papule – a small, solid elevation less than 1.0 centimeter (cm) in diameter; and Pustule – a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions. Intent-to-treat (ITT) population consisted of the entire population enrolled and randomized. The last observation carried forward (LOCF) method was used to impute missing values for inflammatory lesion count.
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End point type |
Primary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Ivermectin 1% Cream + Doxycycline 40 mg MR Capsules v Ivermectin 1% Cream + Oral Placebo Capsules
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Number of subjects included in analysis |
273
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.032 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
Percent Change From Baseline in Inflammatory Lesion Count at Weeks 4 and 8 | ||||||||||||||||||
End point description |
Percent change from baseline in inflammatory lesion count at Weeks 4 and 8 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (i.e. papules and pustules) which were defined as follows: Papule – a small, solid elevation less than 1.0 centimeter in diameter. Pustule – a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions. ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 4 and 8
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Subjects with Clear Inflammatory Lesions at Week 12 | ||||||||||||
End point description |
Percentage of subjects with clear inflammatory lesions at week 12 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (i.e. papules and pustules) which were defined as follows: Papule – a small, solid elevation less than 1.0 cm in diameter. Pustule – a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions. ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.
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End point type |
Secondary
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects With 100 Percent (%) Reduction in Inflammatory Lesions at Weeks 4, 8 and 12 | ||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with 100% reduction in inflammatory lesions at Weeks 4, 8 and 12 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (i.e. papules and pustules) which were defined as follows: Papule – a small, solid elevation less than 1.0 centimeter in diameter. Pustule – a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions. ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 12
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Clinician's Erythema Assessment (CEA) Total Score at Weeks 4, 8 and 12 | |||||||||||||||||||||
End point description |
The evaluator assessed the subject’s diffuse persistent facial erythema of rosacea by performing a static (“snap shot”) evaluation of erythema severity at a social distance of approximately 50 centimeter (cm) using CEA scale, at each visit. CEA is a 5 point scale where 0 = clear (clear skin with no signs of erythema); 1 = almost clear (almost clear; slight redness); 2 = mild (mild erythema; definite redness); 3 = moderate (moderate erythema; marked redness); 4 = severe (severe erythema; fiery redness). A higher score than baseline indicates a worse outcome. ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 12
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Percentage of Subjects in Each Clinician's Erythema Assessment Score Category at Weeks 4, 8 and 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The percentage of subjects in each clinician’s erythema assessment score category was reported. The evaluator assessed the subject’s diffuse persistent facial erythema of rosacea by performing a static (“snap shot”) evaluation of erythema severity at a social distance of approximately 50 centimeter (cm) using CEA scale, at each visit. CEA is a 5 point scale where 0 = clear (clear skin with no signs of erythema); 1 = almost clear (almost clear; slight redness); 2 = mild (mild erythema; definite redness); 3 = moderate (moderate erythema; marked redness); 4 = severe (severe erythema; fiery redness). A higher score than baseline indicates a worse outcome. ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 12
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Investigator's Global Assessment (IGA) Total Score at Weeks 4, 8 and 12 | |||||||||||||||||||||
End point description |
The evaluator assessed the subject’s rosacea by performing a static (“snap shot”) evaluation, at a social distance of approximately 50 cm, using the IGA score. IGA is a 5 point scale where, 0 = clear (no inflammatory lesions present, no erythema); 1 = almost clear (very small papules/pustules, very mild erythema present); 2 = mild (few small papules/pustules, mild erythema); 3 = moderate (severe small or large papules/pustules, moderate erythema); 4 = severe (numerous small and/or large papules/pustules, severe erythema). ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 12
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Percentage of Subjects in Each Investigator's Global Assessment Score Category at Weeks 4, 8 and 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The percentage of subjects in each Investigator’s Global Assessment (IGA) score category was reported. The evaluator assessed the subject’s rosacea by performing a static (“snap shot”) evaluation, at a social distance of approximately 50 cm, using the IGA score. IGA is a 5 point scale where, 0 = clear (no inflammatory lesions present, no erythema); 1 = almost clear (very small papules/pustules, very mild erythema present); 2 = mild (few small papules/pustules, mild erythema); 3 = moderate (severe small or large papules/pustules, moderate erythema); 4 = severe (numerous small and/or large papules/pustules, severe erythema). ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 12
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Stinging/Burning Severity Score at at Weeks 4, 8 and 12 | |||||||||||||||||||||
End point description |
The evaluator recorded the severity of the subject’s facial stinging/burning sensation during the last 24 hours according to the stinging/burning scale. Stinging/burning scale is a 4 point scale where, 0 = none (No stinging/burning ); 1 = mild (slight warm, tingling/stinging sensation, not really bothersome); 2 = moderate (definite warm, tingling/stinging sensation that is somewhat bothersome); 3 = severe (hot, tingling/stinging sensation that has caused definite discomfort). ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 12
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Percentage of Subjects in Each Stinging/Burning Severity Score Category at Weeks 4, 8 and 12 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The percentage of subjects in each stinging/burning severity score category was reported. The evaluator recorded the severity of the subject’s facial stinging/burning sensation during the last 24 hours according to the stinging/burning scale. Stinging/burning scale is a 4 point scale where, 0 = none (No stinging/burning ); 1 = mild (slight warm, tingling/stinging sensation, not really bothersome); 2 = moderate (definite warm, tingling/stinging sensation that is somewhat bothersome); 3 = severe (hot, tingling/stinging sensation that has caused definite discomfort). ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 12
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Global Improvement Total Score at Week 12 (Last Visit/Early Termination) | ||||||||||||
End point description |
Subjects were evaluated for his/her improvement in rosacea compared to his/her rosacea condition before study, using global Improvement scale. It is a 7 item scale where, 0=complete improvement (all signs and symptoms of disease have resolved [100% improvement]); 1=excellent improvement (nearly all signs and symptoms cleared [90% improvement]. Only minimal residual signs and symptoms remain); 2=very good improvement (majority of the signs and symptoms have resolved [about 75% improvement]); 3=good improvement (significant improvement, but many signs and symptoms remain [about 50% improvement]); 4=minimal improvement (slight overall improvement, but not clinically significant [about 25% improvement]); 5=no change (overall severity similar to baseline); 6=worse (worse than baseline). ITT population consisted of the entire population enrolled and randomized. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 12 (last visit/early termination)
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| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects in Each Global Improvement Score Category at Week 12 (Last Visit/Early Termination) | |||||||||||||||||||||||||||||||||
End point description |
Subjects were to evaluated for his/her improvement in rosacea compared to his/her rosacea condition before study, using global Improvement scale. it is a 7 item scale where, 0=complete improvement (all signs and symptoms of disease have resolved [100% improvement]); 1=excellent improvement (nearly all signs and symptoms cleared [90% improvement]. Only minimal residual signs and symptoms remain); 2=very good improvement (majority of the signs and symptoms have resolved [about 75% improvement]); 3=good improvement (significant improvement, but many signs and symptoms remain [about 50% improvement]); 4=minimal improvement (slight overall improvement, but not clinically significant [about 25% improvement]); 5=no change (overall severity similar to baseline); 6=worse (worse than baseline). ITT population consisted of the entire population enrolled and randomized. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Week 12 (last visit/early termination)
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
|
||||||||||||||||
End point title |
Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) | |||||||||||||||
End point description |
An AE was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Safety population (all patients treated [APT]) – consisted of the ITT population, after exclusion of subjects who never used the treatment with certainty based on monitoring report.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From the signing of the informed consent form (ICF) up to Week 12
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
|||||||||||||
End point title |
Dermatology Life Quality Index (DLQI) Questionnaire Total Score at Week 12 (Last Visit/Early Termination Visit) | ||||||||||||
End point description |
DLQI focuses on impact of dermatological diseases on quality of life. It is a 10-item validated quality-of-life questionnaire specific to dermatological conditions. 1) how itchy, sore, painful, stinging, 2) how embarrassed/self-conscious, 3) interfere shopping or looking after home or garden, 4) Influence clothes, 5) affect social/leisure activity, 6) difficult to do sport, 7) prevent from working/studying or If no, problem at work/studying, 8) problem with partner or close friend, 9) cause sexual difficulties, 10) problem caused by treatment. Total score ranged from 0-30,where,0-1=no effect at all on life;2-5=small effect on life; 6-10=moderate effect on life;11-20=very large effect on life;21-30=extremely large effect on life. A higher score indicates a low quality of life due to more severe disease. ITT population consisted of the entire population enrolled and randomised.Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 (last visit/early termination)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects in Each Dermatology Life Quality Index (DLQI) Questionnaire Score Category | ||||||||||||||||||||||||||||||||||||||||||
End point description |
DLQI focuses on impact of dermatological diseases on quality of life. It is a 10-item validated quality-of-life questionnaire specific to dermatological conditions. 1) how itchy, sore, painful, stinging, 2) how embarrassed/self-conscious, 3) interfere shopping or looking after home or garden, 4) Influence clothes, 5) affect social/leisure activity, 6) difficult to do sport, 7) prevent from working/studying or If no, problem at work/studying, 8) problem with partner or close friend, 9) cause sexual difficulties, 10) problem caused by treatment. Total score ranged from 0-30,where,0-1=no effect at all on life;2-5=small effect on life; 6-10=moderate effect on life;11-20=very large effect on life;21-30=extremely large effect on life. A higher score indicates a low quality of life due to more severe disease. ITT population consisted of the entire population enrolled and randomised. Here 'n' (number analyzed) signifies number of subject evaluable for specified categories.
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12 (last visit/early termination)
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Percent Change From Baseline in Dermatology Life Quality Index Questionnaire Total Score at Week 12 (Last Visit/ Early Termination) | ||||||||||||
End point description |
DLQI focuses on impact of dermatological diseases on quality of life. It is a 10-item validated quality-of-life questionnaire specific to dermatological conditions. 1) how itchy, sore, painful, stinging, 2) how embarrassed/self-conscious, 3) interfere shopping or looking after home or garden, 4) Influence clothes, 5) affect social/leisure activity, 6) difficult to do sport, 7) prevent from working/studying or If no, problem at work/studying, 8) problem with partner or close friend, 9) cause sexual difficulties, 10) problem caused by treatment. Total score ranged from 0-30,where,0-1=no effect at all on life;2-5=small effect on life; 6-10=moderate effect on life;11-20=very large effect on life;21-30=extremely large effect on life. A higher score indicates a low quality of life due to more severe disease. ITT population consisted of the entire population enrolled and randomised.Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 12 (last visit/early termination)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
EuroQol-5 Dimension-5 Level (EQ-5D-5L) Questionnaire at Week 12 (Last Visit/Early Termination Visit) | ||||||||||||
End point description |
EQ-5D-5L is a 5-level, 5-dimensional format standardized instrument for use as a measure of health outcome used to assess the impact of study treatments on subject's quality of life as follows: 1) mobility; 2) self-care; 3) usual activities; 4) pain/discomfort; 5) anxiety/depression. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. An increase in the EQ-5D-5L total score indicates improvement. ITT population consisted of the entire population enrolled and randomised. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12/Last visit or early termination visit
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects in Each EuroQol-5 Dimension-5 Level Questionnaire Questions at Baseline and Week 12 (last visit/early termination) | ||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-5L is a 5-level, 5-dimensional format standardized instrument for use as a measure of health outcome used to assess the impact of study treatments on subject's quality of life as follows: 1) mobility; 2) self-care; 3) usual activities; 4) pain/discomfort; 5) anxiety/depression. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. An increase in the EQ-5D-5L total score indicates improvement. ITT population consisted of the entire population enrolled and randomised. Here 'n' (number analyzed) signifies number of subject evaluable for specified categories.
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and Week 12 (last visit/early termination)
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Percentage of Subjects Reported Work Productivity and Activity Impairment: General Health (WPAI:GH) Questionnaire for Currently Employed Question at Week 12 (Last Visit/Early Termination Visit) | ||||||||||||||||||
End point description |
WPAI:GH questionnaire was an instrument to measure impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. Currently Employed question was assessed in this outcome measure. ITT population consisted of the entire population enrolled and randomised. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 12 (Last visit/early termination visit)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Work Productivity and Activity Impairment: General Health (WPAI:GH) Questionnaire at Week 12 (Last Visit/Early Termination Visit) | |||||||||||||||||||||
End point description |
WPAI:GH questionnaire is an instrument to measure impairment in both paid and unpaid work during the past week including questions: missed hours from work because of rosacea?, missed hours from work because of other reason?, number of Working hours. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. ITT population consisted of the entire population enrolled and randomised. Here 'n' (number analyzed) signifies number of subject evaluable for specified categories.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Week 12 (Last visit/Early termination visit)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Work Productivity and Activity Impairment: General Health (WPAI:GH) Questionnaire (How Much Rosacea Affect Productivity at Work, How Much Rosacea Affect Daily Activity) at Week 12 (Last Visit/Early Termination Visit) | ||||||||||||||||||
End point description |
WPAI:GH questionnaire is an instrument to measure impairment in both paid and unpaid work during the past week including questions: 5)how much rosacea affect productivity at work?; 6) how much rosacea affect daily activity?. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. ITT population consisted of the entire population enrolled and randomized. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 12 (Last visit/Early termination visit)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects Reported Satisfied for Subject Satisfaction Questionnaire at Week 12 (Last Visit/Early Termination Visit): Part A | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Subject’s satisfaction questionnaire was used to specifically collect the subjects feedback on the treatment, the level of satisfaction and future usage. Questionnaire consisted of 4 parts: Part A, B, C and D. where Part A consisted of following 12 questions (Q) about study drugs: 1-Time the study regimen took to work, 2-Improvement of facial lesions, 3-Improvement of facial redness, 4-Improvement of ocular symptoms, 5-Improvement of flushing episodes, 6-How bothered by side effects, 7-Your face looks, 8-You feel, 9-Easy to incorporate in daily routine, 10-Using the study regimen again, 11-Overall satisfaction, 12-Compared to last treatment. Satisfied score of questionnaire meant as subjects responded as Very satisfied (Q -1,2,3,4,5,11), Not bothered at all (Q-6),A lot better (Q- 7,8,12), yes (Q-10), strongly agree (Q-9). ITT population consisted of the entire population enrolled and randomised. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 12 (Last visit/early termination visit)
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects Reported Strongly Agree for Subject Satisfaction Questionnaire at Week 12 (Last Visit/Early Termination Visit): Part B | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Part B of Questionnaire consisted of following 10 questions about both provided skin care products cleanser and moisturizer: 1-Easy to incorporate into a daily routine, 2-Recommend to my family or friends, 3-Help my skin look healthier, 4-More confident with rosacea, 5-More confident with skin appearance, 6-Positive difference in the
appearance, 7-Keep using both skin care products, 8-Make my skin more hydrated, 9-Improve the texture of my skin, 10-Pleasant to use. ITT population consisted of the entire population enrolled and randomised. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 12 (Last visit/early termination visit)
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects Reported Strongly Agree for Subject Satisfaction Questionnaire at Week 12 (Last Visit/Early Termination Visit): Part C | ||||||||||||||||||||||||
End point description |
Part C subject satisfaction questionnaire consisted of following 4 questions about the cosmetic product cleanser: 1- Clean healthy skin feeling, 2-Deep cleansing without stripping moisture, 3-Rinsed off easily, 4-Not make my skin feel tight or dry. ITT population consisted of the entire population enrolled and randomised. Here 'N' (subjects analyzed) signifies number of subjects evaluable for this endpoint.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 12 (Last visit or early termination visit)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects Reported Strongly Agree for Subject Satisfaction Questionnaire at Week 12 (Last Visit/Early Termination Visit): Part D | ||||||||||||||||||||||||
End point description |
Part D of subject satisfaction questionnaire consisted of following 4 questions about the cosmetic product moisturizer: 1-Skin feel soft and smooth, 2-Improve my skin moisture, 3-Leave my skin hydrated and protected, 4-Provide comforting sensation.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 12 (Last visit/early termination visit)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
From the signing of the informed consent form (ICF) up to week 12
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
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|
Reporting groups
|
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Reporting group title |
Ivermectin 1% Cream + Doxycycline 40 mg MR Capsules
|
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Reporting group description |
Ivermectin 1% cream: Topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Doxycycline 40 mg MR (30 mg Immediate Release & 10 mg Delayed Release beads) capsules: 1 Capsule once-daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ivermectin 1% Cream + Oral Placebo Capsules
|
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Reporting group description |
Ivermectin 1% cream: Topical to the face, approximately one small pea size amount per facial region (right and left cheeks, forehead, chin, and nose) once a day for 12 weeks. Oral placebo capsules: 1 Capsule once-daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
