Moderate-to-Severe Papulopustular Rosacea and Positive Lactulose Breath Test MedDRA version: 20.0 Level: PT Classification code 10076537 Term: Papulopustular rosacea System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Product Name: Rifaximin delayed release 400 mg
Product Code: Rifaximin-EIR
Pharmaceutical Form: Coated tablet
INN or Proposed INN: RIFAXIMIN
CAS Number: 80621-81-4
Current Sponsor code: Rifaximin-EIR
Sponsors
ALFASIGMA S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All the following criteria must be met both at the Screening (V1) and the Randomization (V2) visit unless otherwise specified. 1)Men and women aged 18 to 70 years at screening (V1) 2)Female participants are eligible if they are: •of non-childbearing potential, i.e.: i) post-menopausal (at least 2 years without spontaneous menses), or ii) surgically sterile (bilateral tubal occlusion, or hysterectomy), or iii) ablation of both ovaries or •of childbearing potential with a negative pregnancy test result at screening and randomization and agreeing to use a highly effective method of contraception (i.e. with failure rate of less than 1% per year) until 72 hours after taking the last study treatment dose. 3)Moderate-to-severe papulopustular rosacea (a.k.a. subtype II, RII,) at screening and confirmed at randomization. Moderate-to-severe rosacea is defined as the presence of 11 or more facial papules or pustules with or without plaques. 4)Positivity of lactulose H2/CH4 breath test (L-BT) within the last 2-weeks before randomization. 5)Patients accepting to provide and legally capable of providing free and informed consent to all procedures included in the protocol (including facial skin photography). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 216 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: All the following criteria must be met both at the Screening (V1) and the Randomization (V2) visit unless otherwise specified. 1)Granulomatous rosacea or rosacea fulminans. 2)Erythematoteleangectatic, phymatous or ocular rosacea only. Patients with these subtypes associated with papulopustular rosacea can be enrolled. 3)Circulating anti-helicobacter pylori IgM and/or IgG at screening (V1). 4)Positivity at the faecal Clostridium Difficile toxin assay at screening (V1). 5)History or family history of inflammatory bowel disease (Crohn’s disease or ulcerative colitis) or other conditions characterized by severe intestinal ulcers. 6)History or family history of coeliac disease. 7)Patients with intestinal obstruction or partial intestinal obstruction. 8)Presence of diarrhoea associated with fever and/or blood in the stool. 9)Health conditions requiring continuous or intermittent treatment with facial topical, inhaled or systemic steroids and/or biologic or non-biologic immunosuppressive or immunomodulatory agents (e.g. autoimmune diseases, etc.). 10)Severe kidney impairment (i.e. estimated glomerular filtration rate <30 ml/min). 11)Severe hepatic impairment (i.e. Child-Pugh B or C). 12)Cancer or any cancer-related treatment within 5 years prior to screening (excluding non-melanoma skin-cancer). 13)History of alcohol or drug abuse within a year prior to screening. 14)Facial skin conditions that can interfere with reliable assessment of rosacea throughout the study (e.g. keloids, hypertrophic scarring, recent facial surgery etc.) 15)Any other significant health condition (e.g. cardiovascular, respiratory, renal, hepatic, neurologic, psychiatric, hematologic, oncologic, immune etc.) that in the investigator’s judgement may: i)jeopardize the patient’s safe participation in the trial or ii)make unlikely the patient’s completion of the study or iii)make unlikely the patient’s compliance with the study procedures (e.g. highly anticipated need of non-permitted treatments, terminal illness, etc.). 16)History of hypersensitivity to rifaximin, rifamycin-derivatives, any of the rifaximin-EIR excipients, or any UV protection cream component. 17)Treatment with biologic immunomodulatory and/or immunosuppressive drugs (e.g. anti-TNF drugs) within 6 months prior to randomization. 18)Treatment with non-biologic immunomodulatory and/or immunosuppressive drugs (e.g. cyclosporine, methotrexate etc.) within 30 days prior to randomization. 19)Treatment with warfarin within 14 days prior to randomization. 20)Treatment with niacin within 30 days prior to randomization. 21)Topical facial or systemic antibiotics within 30 days before randomization; 22)Treatment with neomycin or other low-absorbable oral antibiotics (such as marketed rifaximin) within 90 days before randomization. 23)Topical facial, inhaled or systemic corticosteroids within 30 days prior to randomization. 24)Topical facial retinoids within 30 days before randomization. 25)Systemic retinoids within 6 months before randomization. 26)Any other topical or systemic treatment for rosacea within 30 days before randomization (including also laser and pulsed light, etc.). 27)Pharmaceutical prebiotics and probiotics (functional food is allowed), within 30 days before randomization. 28)Any experimental treatment within 6 months prior to randomization. 29)Women who are pregnant, breast-feeding or planning a pregnancy during the trial period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and efficacy of oral Rifaximin-EIR (rifaximin delayed release) versus placebo in adults with moderate-to-severe papulopustular rosacea (a.k.a. subtype II) and positive lactulose H2/CH4 breath test.;Secondary Objective: To evaluate the degree of concordance between three methods of rosacea grading (clinical direct assessment, centralized expert assessment (dermatologist) from patient’s photographs and centralized assessment (trained technician) from patient’s photographs after computerized advanced processing.;Primary end point(s): The following co-primary efficacy endpoints will be clinically assessed by the Investigator: 1)Mean change from baseline (V2) in number of rosacea inflammatory lesions (papules, pustules or plaques) at V4. 2)Percent of participants showing treatment success (IGA score of 0 [clear] or 1 [almost clear]) at V4 (see Appendix 1 of the protocol.) Success of the study will be declared in any of the active treatment groups if both the co-primary efficacy endpoints will be satisfied (note: the two items may not necessarily occur in the same patient). ;Timepoint(s) of evaluation of this end point: 30 days from randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following endpoints will be assessed using standardized photographs: 1)Mean change from Baseline (V2) in number of rosacea inflammatory lesions at V4 as provided by Canfield Image Analysis. Other secondary efficacy endpoints: The following secondary efficacy endpoints (i.e. from 1 to 5) will be assessed by the investigator: 1)Mean change from Baseline (V2) in number of inflammatory lesions (papules, pustules or plaques) at V3, V5. 2)Percent of participants showing treatment success (i.e. IGA score of 0 or 1) at V3, V5. 3)Percent of participants with IGA score of 0 (clear) at V3, V4, V5. 4)Mean change from Baseline (Randomization, V2) in the following rosacea additional features at V3, V4, V5. •burning or stinging (measured using a 0-10 cm Visual Analogue Scale (VAS)) •telangiectasia (absent=0, mild=1, moderate=2, severe=3) •ocular manifestations (absent=0, mild=1, moderate=2, severe=3), •phymatous changes (absent=0, mild=1, moderate=2, severe=3). 5)Mean change from Baseline in facial non-transient erythema at V3, V4, V5 (absent=0, mild=1, moderate=2, severe=3). The following endpoints (i.e. 6 and 7) will be assessed using standardized photographs: 6)Mean change from Baseline (V2) in number of inflammatory lesions at V3, V5 as provided by Canfield Image Analysis. 7)Mean change from Baseline in facial non-transient erythema score at V3, V4, V5, based on global fractional area redness as provided by Canfield Image Analysis. Additionally, the following secondary endpoints will also be evaluated: 8)Mean change from Baseline in Basic Self-Esteem Scale at V4, V5. 9)Mean change from Baseline in Dermatology Life Quality Index (10-item DLQI) at V4, V5. 10)Mean difference in Treatment Satisfaction Questionnaire between study groups at V4. The following exploratory secondary endpoint will be evaluated at the sites able to collect and store serum samples: 11) Mean change from Baseline in circulating inflamma | — |
Countries
Germany, Italy
Contacts
Public ContactClinical Trials - R&D
ALFASIGMA S.P.A.
Outcome results
None listed