Safety and Efficacy of Rifaximin in Patients With Papulopustular Rosacea and Positive Lactulose Breath Test

Safety and Efficacy of Rifaximin Delayed Release 400 mg Tablets in Patients With Moderate-to-severe Papulopustular Rosacea and Positive Lactulose Breath Test. A Multicenter Double-blind, Placebo-controlled Randomized Clinical Trial

Preliminary evidence suggests that treatment with rifaximin may be beneficial in patients with papulopustular rosacea.

The present clinical trial is aimed to investigate the safety and efficacy of oral 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.

Study Overview

• Status: Unknown
• Conditions: Papulopustular Rosacea
• Intervention / Treatment: Drug: Placebo; Drug: Rifaximin delayed release 400 mg tablet

• Study Type: Interventional
• Enrollment (Anticipated): 236
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Ancona, Italy
    • Recruiting
    • Ospedali Riuniti di Ancona
  • Bari, Italy
    • Recruiting
    • Policlinico di Bari
  • Bologna, Italy
    • Recruiting
    • Policlinico Sant'Orsola Malpighi
  • Brescia, Italy
    • Recruiting
    • Spedali Civili
  • Catania, Italy
    • Recruiting
    • Policlinico Vittorio Emanuele
  • Genova, Italy
    • Recruiting
    • Ospedale Policlinico San Martino
  • Grosseto, Italy
    • Recruiting
    • Ospedale della Misericordia
  • Modena, Italy
    • Recruiting
    • Policlinico di Modena
  • Napoli, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria Federico II
  • Roma, Italy
    • Recruiting
    • Policlinico Universitario A. Gemelli
  • Terni, Italy
    • Recruiting
    • Azienda Ospedaliera Santa Maria
  • Torino, Italy
    • Recruiting
    • A.O.U. Città della Salute e della Scienza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key inclusion Criteria:

1. Men and women aged 18 to 70 years at screening.
2. Female participants are eligible if they are either of non-childbearing potential or 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.
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).

Key exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifaximin-EIR 800 mg BID for 10 days; 2 x rifaximin delayed release 400 mg tablet twice a day (total daily dose of rifaximin: 1600 mg) for 10 days and 2 x placebo tablets twice a day for the following 20 days	Drug: Placebo; Placebo; Drug: Rifaximin delayed release 400 mg tablet; Rifaximin delayed release
Experimental: Rifaximin-EIR 400 mg BID for 30 days; 1 x rifaximin delayed release 400 mg tablet + 1 x placebo tablet twice a day (total daily dose of rifaximin: 800 mg) for 30 days	Drug: Placebo; Placebo; Drug: Rifaximin delayed release 400 mg tablet; Rifaximin delayed release
Experimental: Rifaximin-EIR 400 mg BID for 10 days; 1 x rifaximin delayed release 400 mg tablet + 1 x placebo tablet twice a day (total daily dose of rifaximin: 800 mg) for 10 days and 2 x placebo tablets twice a day for the following 20 days	Drug: Placebo; Placebo; Drug: Rifaximin delayed release 400 mg tablet; Rifaximin delayed release
Placebo Comparator: Two placebo tablets BID for 30 days; 2 x placebo tablets twice a day for 30 days	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline (day 1) in number of rosacea inflammatory lesions (papules, pustules or plaques) at the end of treatment visit (day 30 ± 1)	changes in number of lesions	30 days
Percent of participants showing treatment success (IGA score of 0 [clear] or 1 [almost clear]) at the end of treatment visit (day 30 ± 1)	per cent changes in IGA score 0 and 1 patients	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from Baseline (day 1) in number of rosacea inflammatory lesions at the end of treatment visit (day 30 ± 1) as provided by Canfield Image Analysis	changes respect to baseline	30 days
Mean change from Baseline (day 1) in number of inflammatory lesions (papules, pustules or plaques) at day 10 ± 1 and day 60 ± 3	change respect to baseline	10 and 60 days
Percent of participants showing treatment success (i.e. IGA score of 0 or 1) at day 10 ± 1 and day 60 ± 3	per cent changes in IGA score 0 and 1 patients	10 and 60 days
Percent of participants with IGA score of 0 (clear) at day 10 ± 1, day 30 ± 1 and day 60 ± 3	per cent changes in IGA score 0 patients	10, 30 and 60 days
Mean change from Baseline (day 1) in the following rosacea additional features at day 10 ± 1, day 30 ± 1 and day 60 ± 3: • burning or stinging • telangiectasia • ocular manifestations • phymatous changes	change respect to baseline	10, 30 and 60 days
Mean change from Baseline (day 1) in facial non-transient erythema at day 10 ± 1, day 30 ± 1 and day 60 ± 3 (absent=0, mild=1, moderate=2, severe=3)	change respect to baseline	10, 30 and 60 days
Mean change from Baseline (day 1) in number of inflammatory lesions at day 10 ± 1 and day 60 ± 3 as provided by Canfield Image Analysis	change respect to baseline	10 and 60 days
Mean change from Baseline (day 1) in facial non-transient erythema score at day 10 ± 1, day 30 ± 1 and day 60 ± 3, based on global fractional area redness as provided by Canfield Image Analysis	change respect to baseline	10, 30 and 60 days
Mean change from Baseline in Basic Self-Esteem Scale at day 30 ± 1 and day 60 ± 3	change respect to previous evaluation	30 and 60 days
Mean change from Baseline (day 1) in Dermatology Life Quality Index (10-item DLQI) at day 30 ± 1 and day 60 ± 3	change respect to baseline	30 and 60 days
Mean difference in Treatment Satisfaction Questionnaire between study groups at day 30 ± 1	differences between treatment arms	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from Baseline (day 1) in circulating inflammatory marker levels at 10 ± 1, day 30 ± 1 and day 60 ± 3	change respect to baseline	10, 30 and 60 days
Mean change from baseline (day 1) skin texture index at 10 ± 1, day 30 ± 1 and day 60 ± 3 as provided by Canfield Image Analysis	change respect to baseline	10, 30 and 60 days

Collaborators and Investigators

• Sponsor: Alfasigma S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2018
• Primary Completion (Anticipated): April 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 11, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

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: REROS/001/17; 2017-003722-33 (EudraCT Number)

Drug and device information, study documents

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