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

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• has used bowel prep, laxative, or enema within 30 days prior to Day 1.
• bleeding disorder including, but not limited to, acquired or congenital platelet function defects, disseminated intravascular coagulation (DIC), bleeding factor deficiencies, hemophilia, idiopathic thrombocytopenia purpura (ITP), or von Willebrand's disease.
• planning to undergo a major surgical procedure during the duration of the study.
• positive test for human immunodeficiency virus (HIV)1 or HIV2.
• active Hepatitis B infection (HBsAg positive). Prior infection that is not active (i.e., HBsAg negative, HBcAb positive, and HBsAb po