Pharmacokinetics and Pharmacodynamics of Rifaximin Novel Formulations in Patients With Sickle Cell Disease

NCT05098028 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RBSC2161
• Study Type: interventional
• Target: 44
• Locations: 3 countries
• Sites: 8

Brief Summary

This is a randomized, double-blind, placebo-controlled study in sickle cell disease participants with a history of Vaso-occlusive Crises (VOCs). Approximately 60 participants with sickle cell disease will be enrolled and randomized: 12 participants in each of four active novel formulation rifaximin groups and 6 participants in each of 2 placebo groups.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Maximum Plasma Concentration

  Maximum observed plasma concentration

  Day 29

Study Arms (5)

Low Dose Rifaximin ER

EXPERIMENTAL

twice daily

Drug: Low Dose Rifaximin ER

Low Dose Rifaximin DER

EXPERIMENTAL

twice daily

Drug: Low Dose Rifaximin DER

High Dose Rifaximin ER

EXPERIMENTAL

twice daily

Drug: High Dose Rifaximin ER

High Dose Rifaximin DER

EXPERIMENTAL

twice daily

Drug: High Dose Rifaximin DER

Placebo

PLACEBO COMPARATOR

twice daily

Drug: Placebo

Interventions

Low Dose Rifaximin ER DRUG

Low Dose Rifaximin Extended Release Twice Daily

Low Dose Rifaximin ER

Low Dose Rifaximin DER DRUG

Low Dose Rifaximin Delayed Extended Release Twice Daily

Low Dose Rifaximin DER

High Dose Rifaximin ER DRUG

High Dose Rifaximin Extended Release Twice Daily

High Dose Rifaximin ER

High Dose Rifaximin DER DRUG

High Dose Rifaximin Delayed Extended Release Twice Daily

High Dose Rifaximin DER

Placebo DRUG

Placebo Twice Daily

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ability and willingness to sign a written informed consent form.
• between the ages of 18 to 70 years old (inclusive) at the time of consent.
• SCD of any genotype (HbSS, HbSC, HbS β-thalassemia). If the subject's genotype has not been previously documented, genotyping will be performed during Screening using high-performance liquid chromatography (HPLC)/electrophoresis.
• least 2 VOCs within the 12 months prior to Screening.
• if receiving hydroxyurea (HU)/hydroxycarbamide (HC), subject must have been receiving the treatment for at least 6 months prior to Screening and must agree to maintain the same dose and schedule for the duration of the study.
• must have laboratory values at Screening as follows:
• Absolute Neutrophil Count ≥1.0 x 109/L
• Platelets ≥ 75 x 109/L
• Hemoglobin (Hgb) ≥ 6.0 g/dL
• Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2 using the CKD-EPI formula
• Total bilirubin ≤ 15 mg/dL
• Alanine transaminase (ALT) ≤ 3.0 x ULN
• International Normalized Ratio (INR) ≤ 2.0
• Eastern Cooperate Oncology Group (ECOG) performance status ≤ 2
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test at Screening and agree to use standard prevention methods for the duration of the study.

You may not qualify if:

• receiving concomitant treatment with voxelotor, crizanlizumab, or L-glutamine.
• any history of stem cell transplant, is planning to begin or has received in past 30 days.
• acute VOC, requiring a visit to a medical facility and/or healthcare professional, ending within 7 days prior to Day 1 dosing.
• has received any blood products within 30 days prior to Day 1 dosing.
• uncontrolled liver disease or renal impairment, ulcerative colitis, Crohn's disease, or other chronic GI disorder.
• has received active treatment in another investigational trial within 30 days or 5 half-lives of the last dose of the investigational agent, whichever is greater, prior to Screening.
• has received penicillin prophylaxis or antibiotics for treatment of infection within 30 days or 5 half-lives of the treatment, whichever is greater, prior to Screening.
• significant medical condition that required hospitalization (other than for a VOC) within 2 months prior to Screening.
• planning on undergoing an exchange transfusion during the duration of the study or has completed one within 4 weeks prior to Day 1 dosing.
• hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any components of rifaximin ER and DER.
• pregnant or a nursing woman.
• history of illicit drug use or abuse, either documented or in the opinion of the Investigator.
• using any medication that is known to inhibit or induce CYP3A4, or P-gp and OATP1B1/B3 within 30 days or 5 half-lives, whichever is longer, prior to Day 1 dosing, or in the opinion of the Investigator, may affect the evaluation of the study product or place the subject at undue risk.
• has had any prior gastrointestinal surgery which has altered the anatomy of the esophagus, stomach, or small/large intestine (with the exception of appendectomy, cholecystectomy, and fundoplication).
• has had a colonoscopy or sigmoidoscopy within 30 days prior to Day 1 or plans to undergo such a procedure during the duration of the study.

Sponsors & Collaborators

• Bausch Health Americas, Inc.: lead

Study Sites (8)

Bausch Site 105

Orange, California, 92868, United States

Location

Bausch Site 103

Denver, Colorado, 80220, United States

Location

Bausch Site 104

Atlanta, Georgia, 30329, United States

Location

Bausch Site 101

Syracuse, New York, 13210, United States

Location

Bausch Site 102

Greenville, North Carolina, 27834, United States

Location

Bausch Site 201

Montreal, Quebec, H2X 3E4, Canada

Location

Bausch Site 501

Eldoret, 30100, Kenya

Location

Bausch Site 502

Kisumu, 40100, Kenya

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Varsha Bhatt
• Organization: Bausch Health Americas, Inc

varsha.bhatt@bauschhealth.com

7072301712

Study Officials

• Varsha Bhatt

  Bausch Health

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: October 28, 2021
• Study Start: March 22, 2022
• Primary Completion: September 4, 2023
• Study Completion: September 4, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); KE (2); US (5)