E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Persistent redness on the central facial area including the cheeks, forehead and chin
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039218 |
E.1.2 | Term | Rosacea |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this study is to assess the patients' feedback following the treatment of severe facial redness of rosacea with brimonidine tartrate 0.5% gel compared with placebo. |
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E.2.2 | Secondary objectives of the trial |
The efficacy and tolerance of the treatment will be assessed |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible for the study, subjects must fulfil all of the following criteria. 1.Male or female subjects age of 18 years or older, 2.A clinical diagnosis of facial rosacea, 3.A PSA score of 4 (severe) at Baseline prior to the study drug application, 4.A Clinician’s Erythema Assessment (CEA) score of 3 (moderate) or 4 (severe) at Baseline prior to the study drug application, 5.Females of childbearing potential with a negative urine pregnancy test (UPT) at Baseline and must practice an effective method of contraception during the study: oral/systemic (injectable, patch, etc.) contraception (must have been on a stable dose for 3 months prior to study entry), intrauterine device, bilateral tubal ligation, strict abstinence, condoms, diaphragms, sponge, spermicides or partner had a vasectomy, 6.Females of non-childbearing potential, i.e., premenses, post-menopausal (absence of menstrual bleeding for 2 years), hysterectomy, or bilateral ovariectomy, are not required to have a UPT at Baseline, 7.Subjects willing and capable of complying with the extent and degree required by the protocol, 8.Subjects understand and sign an Informed Consent Form at Baseline, prior to any investigational procedure being performed. Rationale: 1-4: In order to select a suitable population for the clinical trial 5-6: Due to limited amount of data on human pregnancy 7: In order to ensure compliance to the clinical trial 8: Only subjects who provided written consent/authorisation are allowed to participate in this clinical trial.
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E.4 | Principal exclusion criteria |
Any subject who meets one or more of the following criteria will not be eligible for the study. 1.More than 5 facial inflammatory lesions (papules or pustules) of rosacea, 2.Particular forms of rosacea (rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin) or other concomitant facial dermatoses that share clinical features with rosacea such as peri-oral dermatitis, demodicidosis, facial keratosis pilaris, seborrheic dermatitis, acute lupus erythematosus, or actinic telangiectasia, 3.Current treatment with monoamine oxidase inhibitors, barbiturates, opiates, sedatives, systemic anaesthetics, or alpha agonists, 4.Less than 3 months stable dose treatment for inflammatory lesions of rosacea, tricyclic anti-depressants, cardiac glycosides, beta blockers or other antihypertensive agents, 5.Current diagnosis of Raynaud’s syndrome, thromboangiitis obliterans, orthostatic hypotension, severe cardiovascular disease, cerebral or coronary insufficiency, renal or hepatic impairment, scleroderma, Sjögren’s syndrome, or depression, 6.Any uncontrolled chronic or serious disease or medical condition that may either interfere with the interpretation of the clinical trial results, or put the subject at significant risk if the subject participates in the clinical trial as judged by the investigator, 7.Known or suspected allergies or sensitivities to any component of the study drugs, including the active ingredient brimonidine tartrate (see Investigator’s Brochure), 8.The subject has received, applied or taken the following treatments within the specified time frame prior to the Day 1 visit: Topical facial treatments or procedures: -Any dermatologic/surgical procedure on the face: 4 weeks -Prescription medications that are indicated, wholly or in part, as a treatment for erythema of rosacea: 4 weeks -Prescription medications for treatment of acne: 4 weeks -Immunomodulators: 4 weeks -Corticosteroids: 4 weeks -Antibiotics other than those intended for the treatment of inflammatory lesions of rosacea: 2 weeks -OTC medications for treatment of acne: 1 week -Astringents or abrasives: 2 days Systemic treatments: -Isotretinoin: 6 months -Immunomodulators: 12 weeks -Prescription medications that are indicated, wholly or in part, as a treatment for erythema of rosacea: 4 weeks -Prescription medications for treatment of acne: 4 weeks -Corticosteroids (oral or injectable): 4 weeks -Phototherapy: 4 weeks -Antibiotics other than those intended for the treatment of inflammatory lesions of rosacea: 4 weeks -Prescription anti-inflammatory medications: 2 weeks -Chronic, daily use of OTC anti-inflammatory medications (e.g. ibuprofen, naproxen) for more than 1 week (does not include low-dose aspirin for cardiac prophylaxis: 1 week -Niacin ≥500 mg per day: 1 week 9.Female who is pregnant or lactating, 10.Exposed to excessive ultraviolet (UV) radiation within one week prior to the Day 1 visit, 11.Presence of beard or excessive facial hair on Day 1, which would interfere with the study treatments or study assessments and refusal to remove for duration of the study, 12.Prior treatment with brimonidine tartrate gel, 13.Current treatment with brimonidine tartrate ophthalmic solution, 14.Current treatment with any topical facial formulation containing brimonidine tartrate or oxymetazoline, 15.Subjects unwilling to refrain from use of prohibited medication or excessive exposition to UV during the course of the study, 16.Vulnerable subjects (such as deprived from freedom) as defined in Section 1.61 of International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (GCP), 17.Current participation in any other clinical trial of a drug or device OR participated within 30 days prior to Day 1 OR in an exclusion period from a previous clinical trial (when possible). Rationale: 1, 2: In order to select subjects with suitable rosacea severity and avoid any interference or confounding factors with evaluation 3-7: To avoid potential safety concerns with use of the study drug 8, 10-15: To avoid any interference or confounding factors with the study outcomes and interpretation of results 9: Due to limited amount of data regarding human pregnancy or lack of data about the brimonidine excretion in human milk 16-17: To comply with ICH-GCP
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E.5 End points |
E.5.1 | Primary end point(s) |
There is no primary endpoint in the study, as this is an exploratory study and no previous analysis on patient-reported outcomes of brimonidine tartrate 0.5% gel exists for the calculation of sample size. Variables to be analysed in the study include the following:
Patient-reported outcomes: • Dermatology Life Quality Index questionnaire at each visit • Facial Redness questionnaire at each visit • EuroQol-5 Dimension questionnaire at each visit • Subject Satisfaction questionnaire at the end of the study Efficacy variables: • Severity of erythema according to participants before and 3 hours after application of study drug • Severity of erythema according to study doctors before and 3 hours after application of study drug Safety variable: • Incidence of adverse event
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E.5.2 | Secondary end point(s) |
Not applicable. See above for all variables to be analysed in the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient-reported outcomes |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |