Clinical trial NCT05150587: Safety, Efficacy and Pharmacokinetics of Rifaximin in Patients With Moderate-to-severe Papulopustular Rosacea
Official title: A Phase IIa, Multicenter, Double Blind, Placebo Controlled, Randomized Clinical Trial to Assess Safety, Efficacy and Pharmacokinetics of Rifaximin Delayed-Release (Rifaximin-EIR) in Patients With Moderate-to-severe Papulopustular Rosacea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Papulopustular Rosacea
Lead sponsor: Alfasigma S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: bioRASI, LLC
First posted: 2021-12-09
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rosacea is a common chronic inflammatory relapsing-remitting skin condition almost exclusively affecting the central area of the face and the eyes.

Preliminary evidence suggests that treatment with rifaximin, a poorly absorbed oral antibiotic drug may be beneficial in patients with rosacea, particularly in those with papulopustular phenotype and positivity to Lactulose Breath Test (L-BT).

The objective of this study is twofold:

1. To explore the safety and efficacy of 2 doses of oral Rifaximin versus placebo in adults with moderate-to-severe papulopustular rosacea.
2. To assess the pharmacokinetics (PK) of these two dose regimens in a sub-group of patients.


Eligibility criteria: Main Inclusion Criteria:

* Men and women aged 18 years or older at screening.
* Female participants are eligible if they are: i) of non-childbearing potential or ii) of childbearing potential with a negative pregnancy test result at screening and randomization AND agreeing to use a highly effective method of contraception until 72 hours after taking the last study treatment dose.
* Presence of rosacea, papulopustular phenotype.
* Presence of ≥11 and ≤70 facial papules and/or pustules.
* Moderate or severe rosacea based on Investigator's Global Assessment based on Investigator's judgement.
* Patients accepting to provide and legally capable of providing free and informed consent to all procedures included in the protocol (including the availability to perform a Lactulose Breath Test).

Main Exclusion Criteria:

* Granulomatous rosacea or rosacea fulminans.
* Erythematotelangiectatic, phymatous or ocular rosacea only. Patients with these subtypes associated with papulopustular rosacea can be enrolled.
* Rosacea with Investigator's Global Assessment (IGA) grade ≤2 based on Investigator's judgment.
* Anticipated need for proctoscopy or colonoscopy within two weeks after lactulose breath test.
* Subjects requiring a low galactose diet.
* Hypersensitivity or intolerance to lactulose or any excipient of the lactulose reparation to be used for L-BT.
* History of inflammatory bowel disease (Crohn's disease or ulcerative colitis) or other conditions characterized by severe intestinal ulcers.
* History of coeliac disease.
* Patients with intestinal obstruction or partial intestinal obstruction.
* Presence of diarrhoea associated with fever and/or blood in the stool.
* Severe kidney impairment (i.e. estimated glomerular filtration rate \<30 ml/min).
* Severe hepatic impairment (i.e. Child-Pugh B or C).
* Cancer or any cancer-related treatment within 5 years prior to screening (excluding non-melanoma skin-cancer).
* History of alcohol or drug abuse within a year prior to screening, based on Investigator's judgement.
* Facial skin conditions that can interfere with reliable assessment of rosacea throughout the study (e.g. facial hair, tattoos, other facial adornments, keloids, hypertrophic scarring, recent facial surgery, excessive sun exposure including use of tanning beds)
* Any other significant health condition (e.g. cardiovascular, respiratory, renal, hepatic, neurologic, psychiatric, hematologic, oncologic, immune etc.) or non-health condition 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.).
* History of hypersensitivity to the study drug.
* Treatment with biologic immunomodulatory and/or immunosuppressive drugs (e.g. anti-tumor necrosis factor \[TNF\] drugs) within 6 months prior to randomization.
* Treatment with non-biologic immunomodulatory and/or immunosuppressive drugs (e.g. cyclosporine, methotrexate etc.) within 30 days prior to randomization.
* Treatment with warfarin (or other coumarins) within 14 days prior to randomization.
* Treatment with niacin within 30 days prior to randomization.
* Topical facial or systemic antibiotics within 30 days before randomization;
* Treatment with neomycin or other low-absorbable oral antibiotics within 90 days before randomization.
* Topical facial, inhaled or systemic corticosteroids within 30 days prior to randomization.
* Topical facial retinoids within 30 days before randomization.
* Systemic retinoids within 6 months before randomization.
* Any other topical or systemic treatment for rosacea within 30 days before randomization (including also laser and pulsed light, etc.).
* Over-the-counter intestinal or topical skin probiotics (functional food is allowed), within 30 days before randomization.
* Any experimental treatment within 6 months prior to randomization.
* Current swab-positive or suspected (under investigation) Covid-19 infection; or fever and one or more of the following respiratory disease signs or symptoms: cough, sputum production, shortness of breath within the last 14 days; or contact with people with Covid-19 infection within the last 14 days.
* Women who are pregnant, breast-feeding or planning a pregnancy during the trial period.
* Subjects who are investigational site staff members and their family members, site staff members otherwise supervised by the investigator, or patients who are Alfasigma's employees.

Primary outcomes:
measure: Co-primary Endpoint: Change From Baseline in Number of Rosacea Inflammatory Lesions
timeFrame: 30 days
measure: Co-primary Endpoint: Treatment Success Rate
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Yuma
country: United States
facility: Dermatology Research Ventures
state: Arizona
city: Fort Smith
country: United States
facility: Johnson Dermatology
state: Arkansas
city: Long Beach
country: United States
facility: Long Beach Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Metropolis Dermatology
state: California
city: Los Angeles
country: United States
facility: LA Universal Research Center
state: California
city: San Diego
country: United States
facility: Cosmetic Laser Dermatology
state: California
city: San Diego
country: United States
facility: UCSD
state: California
city: San Diego
country: United States
facility: University Clinical Trials, Inc.
state: California
city: Boca Raton
country: United States
facility: Skin Care Research
state: Florida
city: Brandon
country: United States
facility: MOORE Clinical Research,Inc.
state: Florida
city: Hialeah
country: United States
facility: Sweet Hope Research Specialty, Inc.
state: Florida
city: Miami Lakes
country: United States
facility: Savin Medical Group
state: Florida
city: Ormond Beach
country: United States
facility: Leavitt Medical Associates of Florida
state: Florida
city: Marietta
country: United States
facility: DelRicht Research
state: Georgia
city: Clarksville
country: United States
facility: DS Research
state: Indiana
city: Louisville
country: United States
facility: Skin Science PLLC
state: Kentucky
city: Louisville
country: United States
facility: DS Research
state: Kentucky
city: Baton Rouge
country: United States
facility: Delricht Research Baton Rouge LA
state: Louisiana
city: Covington
country: United States
facility: Delricht Research Covington LA
state: Louisiana
city: Houma
country: United States
facility: DelRicht Research Houma Louisiana
state: Louisiana
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Troy
country: United States
facility: Revival Research Institute, LLC.
state: Michigan
city: Wyandotte
country: United States
facility: Grekin Skin Care Institute
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: JDR Dermatology Research
state: Nevada
city: New York
country: United States
facility: JUVA Skin and Laser Center
state: New York
city: Charlotte
country: United States
facility: Onsite Clinical Solutions
state: North Carolina
city: High Point
country: United States
facility: Dermatology Consulting Services, PLLC
state: North Carolina
city: Tulsa
country: United States
facility: DelRicht Research
state: Oklahoma
city: Portland
country: United States
facility: Oregon Dermatology and Research Center
state: Oregon
city: Philadelphia
country: United States
facility: Paddington Testing Co, Inc
state: Pennsylvania
city: Dallas
country: United States
facility: Dermatology Treatment and Research Center
state: Texas
city: El Paso
country: United States
facility: 3A Research
state: Texas
city: Frisco
country: United States
facility: DelRicht Research Frisco Texas
state: Texas
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Velocity Clinical Research
state: Utah
city: Richmond
country: United States
facility: West End Dermatology Associates
state: Virginia
Study officials:
References: