Randomised, Placebo-controlled Safety and Pharmacokinetics Study of Novel Rifaximin Formulations in Healthy Volunteers

A Randomised, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Rifaximin Formulations in Healthy Volunteers

Phase 1, Randomised, Placebo-Controlled, Single-Ascending Dose and Multiple-Dose with 3 novel RIFAXIMIN Formulations.

2 phases: Single-Ascending Dose (SAD) Phase and a Multiple-Dose (MD) Phase, Plus optional open-label, crossover Food Effect (FE) Evaluation

Primary objective: evaluate the safety and tolerability of three novel formulations of rifaximin in healthy volunteers.

Secondary objective: evaluate the pharmacokinetics (PK) of the novel formulations and to assess for the presence of exploratory biomarkers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Rifaximin Novel Formulation

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand
      • Auckland Clinical Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participant has the ability and willingness to sign a written informed consent, is either male or female aged between 18 and 65 years, inclusive, at the time of informed consent, is in good general health, and has a body mass index (BMI) at least 18 kg/m2 and at most 34 kg/m2, and a minimum body weight of 45 kg.
• The participant must have suitable venous access for blood sampling and be able and willing to complete the study and comply with all study instructions and attend the necessary visits.
• A negative pregnancy test is required for all women of child-bearing potential (WOCBP). WOCBP and men must agree to use highly effective contraception methods from screening through the end of the study. Follicle stimulating hormone (FSH) testing will be conducted for post-menopausal women without surgical evidence of sterility (total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).

Exclusion Criteria:

• Female participant who is pregnant, trying to become pregnant, or breast feeding.
• Participant with a known or suspected intolerance to rifaximin or the excipients used in the novel formulations.
• Participant has had any major illness or systemic infection (including COVID [coronavirus disease] -19) within 4 weeks of the Screening Visit or has a clinically relevant history or currently suffering from any disease or condition that, in the opinion of the Investigator, may affect the evaluation of the study product or place the participant at undue risk. Participant has liver function tests >1.1x the upper limit of normal or any other abnormal laboratory test that the Investigator deems as clinically significant.
• Participant has human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, a clinically relevant history of or current evidence of abuse of alcohol or other drugs. Participant is currently a tobacco smoker or was a tobacco smoker within 6 months of the Baseline Visit.
• Participant has received any investigational product within 4 weeks or 5 half-lives of the product, whichever is greater, prior to the Baseline Visit or is scheduled to receive an investigational product (other than the study product) or is scheduled for a medical procedure during the study period. Participant is taking probiotics.
• Participant is taking any medications which are known cytochrome P450 3A (CYP3A) or P-glycoprotein (Pgp) inhibitors/inducers or is currently using any medication that, in the opinion of the Investigator, may affect the evaluation of the study product or place the participant at undue risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Formulation 1 - Low Dose; Rifaximin Formulation 1 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 1 Capsules - Mid Dose; Rifaximin Formulation 1 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 1 Capsules - High Dose; Rifaximin Formulation 1 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 1 Capsules - Max Dose; Rifaximin Formulation 1 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
PLACEBO_COMPARATOR: Formulation 1 Capsules - Placebo; Placebo Formulation 1 Capsules	Drug: Placebo; Placebo
EXPERIMENTAL: Formulation 2 - Low Dose; Rifaximin Formulation 2 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 2- Mid Dose; Rifaximin Formulation 2 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 2 - High Dose; Rifaximin Formulation 2 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 2 - Max Dose; Rifaximin Formulation 2 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
PLACEBO_COMPARATOR: Formulation 2 - Placebo; Placebo Formulation 2 Capsules	Drug: Placebo; Placebo
EXPERIMENTAL: Formulation 3 - Low dose; Rifaximin Formulation 3 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 3 - Mid dose; Rifaximin Formulation 3 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 3 - High dose; Rifaximin Formulation 3 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
EXPERIMENTAL: Formulation 3 - Max dose; Rifaximin Formulation 3 Capsules	Drug: Rifaximin Novel Formulation; Rifaximin Novel Formulation
PLACEBO_COMPARATOR: Formulation 3 - Placebo; Placebo Formulation 3 Capsules	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with adverse events	Up to 18 days

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Investigators: Principal Investigator: Christian Schwabe, MD, Auckland Clinical Studies

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 24, 2020
• Primary Completion (ACTUAL): May 9, 2021
• Study Completion (ACTUAL): May 9, 2021

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (ACTUAL): August 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: RBPK1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes