Safety, Efficacy and Pharmacokinetics of Rifaximin in Patients With Moderate-to-severe Papulopustular Rosacea

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

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.

Study Overview

• Status: Completed
• Conditions: Papulopustular Rosacea
• Intervention / Treatment: Drug: Placebo; Drug: Rifaximin

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Yuma, Arizona, United States, 85365
      • Dermatology Research Ventures
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Johnson Dermatology
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials
    • Los Angeles, California, United States, 90017
      • Metropolis Dermatology
    • Los Angeles, California, United States, 90057
      • LA Universal Research Center
    • San Diego, California, United States, 92121
      • Cosmetic Laser Dermatology
    • San Diego, California, United States, 92123
      • University Clinical Trials, Inc.
    • San Diego, California, United States, 92122
      • UCSD
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Skin Care Research
    • Brandon, Florida, United States, 33511
      • MOORE Clinical Research,Inc.
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty, Inc.
    • Miami Lakes, Florida, United States, 33014
      • Savin Medical Group
    • Ormond Beach, Florida, United States, 32174
      • Leavitt Medical Associates of Florida
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Delricht Research
  • Indiana
    • Clarksville, Indiana, United States, 47129
      • DS Research
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • DS Research
    • Louisville, Kentucky, United States, 401217
      • Skin Science PLLC
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Delricht Research Baton Rouge LA
    • Covington, Louisiana, United States, 70433
      • Delricht Research Covington LA
    • Houma, Louisiana, United States, 70360
      • DelRicht Research Houma Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Delricht Research
  • Michigan
    • Troy, Michigan, United States, 48084
      • Revival Research Institute, LLC.
    • Wyandotte, Michigan, United States, 48192
      • Grekin Skin Care Institute
  • Missouri
    • Saint Joseph, Missouri, United States, 65406
      • MediSearch Clinical Trials
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • JDR Dermatology Research
  • New York
    • New York, New York, United States, 10022
      • JUVA Skin and Laser Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services, PLLC
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74114
      • Delricht Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Co, Inc
  • Texas
    • Dallas, Texas, United States, 75230
      • Dermatology Treatment and Research Center
    • El Paso, Texas, United States, 79925
      • 3A Research
    • Frisco, Texas, United States, 75034
      • DelRicht Research Frisco Texas
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Velocity Clinical Research
  • Virginia
    • Richmond, Virginia, United States, 23233
      • West End Dermatology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablets
Active Comparator: Rifaximin 250 mg TID	Drug: Rifaximin; Rifaximin tablets
Active Comparator: Rifaximin 500 mg TID	Drug: Rifaximin; Rifaximin tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-primary Endpoint: Change From Baseline in Number of Rosacea Inflammatory Lesions	This is a co-primary endpoint. Success of the study will be declared in any of the active treatment groups if both the co-primary efficacy endpoints (here listed as 1 and 2) will be satisfied (note: the two items may not necessarily occur in the same patient): Mean change from Baseline in number of rosacea inflammatory lesions (papules, pustules or plaques) at the end of treatment;; Percent of participants showing treatment success defined as IGA (Investigator's Global Assessment) score of 0 or 1 (0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe) at the end of treatment.	30 days
Co-primary Endpoint: Treatment Success Rate	This is a co-primary endpoint. Success of the study will be declared in any of the active treatment groups if both the co-primary efficacy endpoints (here listed as 1 and 2) will be satisfied (note: the two items may not necessarily occur in the same patient): Mean change from Baseline in number of rosacea inflammatory lesions (papules, pustules or plaques) at the end of treatment;; Percent of participants showing treatment success defined as IGA (Investigator's Global Assessment) score of 0 or 1 (0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe) at the end of treatment.	30 days

Collaborators and Investigators

• Sponsor: Alfasigma S.p.A.
• Collaborators: bioRASI, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Actual): October 20, 2022
• Study Completion (Actual): October 20, 2022

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Rosacea; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: RE-ROS2002-2021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No