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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Rifaximin Novel Formulation
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Formulation 1 - Low Dose<br>Rifaximin Formulation 1 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 1 Capsules - Mid Dose<br>Rifaximin Formulation 1 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 1 Capsules - High Dose<br>Rifaximin Formulation 1 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 1 Capsules - Max Dose<br>Rifaximin Formulation 1 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Placebo Comparator: Formulation 1 Capsules - Placebo<br>Placebo Formulation 1 Capsules | Drug: Placebo<br>* Placebo<br>|
| Experimental: Formulation 2 - Low Dose<br>Rifaximin Formulation 2 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 2- Mid Dose<br>Rifaximin Formulation 2 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 2 - High Dose<br>Rifaximin Formulation 2 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 2 - Max Dose<br>Rifaximin Formulation 2 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Placebo Comparator: Formulation 2 - Placebo<br>Placebo Formulation 2 Capsules | Drug: Placebo<br>* Placebo<br>|
| Experimental: Formulation 3 - Low dose<br>Rifaximin Formulation 3 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 3 - Mid dose<br>Rifaximin Formulation 3 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 3 - High dose<br>Rifaximin Formulation 3 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Experimental: Formulation 3 - Max dose<br>Rifaximin Formulation 3 Capsules | Drug: Rifaximin Novel Formulation<br>* Rifaximin Novel Formulation<br>|
| Placebo Comparator: Formulation 3 - Placebo<br>Placebo Formulation 3 Capsules | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

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