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Trial details
Pharmacokinetics and Pharmacodynamics of Rifaximin Novel Formulations in Patients With Sickle Cell Disease
Current status:
Approved
|
Date registered:
09/01/2023
Trial version(s)
History: 27/07/2022
History: 27/07/2022
Current: 27/07/2022
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Main Information
Primary registry identifying number
LBCTR2022095104
Protocol number
RBSC2161
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
29/09/2022
Primary sponsor
Bausch Health LLC
Primary sponsor: Country of origin
United States of America
Public title
Pharmacokinetics and Pharmacodynamics of Rifaximin Novel Formulations in Patients With Sickle Cell Disease
Acronym
Scientific title
A Phase 2a Randomized, Double-Blind, Placebo-Controlled Study to Characterize the Pharmacokinetics and Pharmacodynamics of Rifaximin Novel Formulations in Patients With Sickle Cell Disease
Acronym
Brief summary of the study: English
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.
Brief summary of the study: Arabic
هذه دراسة عشوائية مزدوجة التعمية يتم التحكم فيها بالعلاج الوهمي في المشاركين في مرض الخلايا المنجلية الذين لديهم تاريخ من أزمات انسداد الأوعية الدموية (VOCs). سيتم تسجيل ما يقرب من 60 مشاركًا مصابًا بمرض الخلايا المنجلية وتوزيعهم عشوائيًا: 12 مشاركًا في كل من أربع مجموعات ريفاكسيمين ذات تركيبة جديدة نشطة و 6 مشاركين في كل مجموعة من مجموعتي العلاج الوهمي.
Health conditions/problem studied: Specify
Sickle Cell Disease patients with history of VOCs
Interventions: Specify
Subjects will be enrolled and randomized 2:2:1:2:2:1 to one of 6 parallel arms to receive oral treatment twice daily (BID) for approximately 29 days: • Group 1: 40 mg rifaximin ER, BID • Group 2: 40 mg rifaximin DER, BID • Group 3: Placebo for 40 mg rifaximin, BID • Group 4: 80 mg rifaximin ER, BID • Group 5: 80 mg rifaximin DER, BID • Group 6: Placebo for 80 mg rifaximin, BID
Key inclusion and exclusion criteria: Inclusion criteria
A subject will be eligible for inclusion in this study if he/she meets all the following criteria: 1. Subject must have the ability and willingness to sign a written informed consent form. 2. Subject is between the ages of 18 to 70 years old (inclusive) at the time of consent. 3. Subject has 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. 4. Subject must have experienced at least 2 VOCs within the 12 months prior to Screening. A VOC is defined as: a. The occurrence of appropriate symptoms consistent with a painful crisis, acute chest syndrome (ACS), or priapism (Section 2.2.3) , and b. Requires a visit to a medical facility and/or healthcare professional, and c. Receipt of either a parenteral or oral opioid or NSAID analgesia. 5. If subject is 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. 6. Subjects must have laboratory values at Screening as follows: a. Absolute Neutrophil Count (ANC) ≥1.0 x 109/L b. Platelets ≥ 75 x 109/L c. Hemoglobin (Hgb) ≥ 6.0 g/dL d. Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2 using the CKD-EPI formula e. Total bilirubin ≤ 15 mg/dL f. Alanine transaminase (ALT) ≤ 3.0 x ULN g. International Normalized Ratio (INR) ≤ 2.0 7. Eastern Cooperate Oncology Group (ECOG) performance status ≤ 2 8. 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.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
70
Key inclusion and exclusion criteria: Exclusion criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Subject is receiving concomitant treatment with voxelotor, crizanlizumab, or L-glutamine. 2. Subject has any history of stem cell transplant, is planning to begin or has received in past 30 days. 3. Subject experiences an acute VOC, requiring a visit to a medical facility and/or healthcare professional, ending within 7 days prior to Day 1 dosing. 4. Subject has received any blood products within 30 days prior to Day 1 dosing. 5. Subject has uncontrolled liver disease or renal impairment, ulcerative colitis, Crohn’s disease, or other chronic GI disorder. 6. Subject 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. 7. Subject 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. 8. Subject has a significant medical condition that required hospitalization (other than for a VOC) within 2 months prior to Screening. 9. Subject is planning on undergoing an exchange transfusion during the duration of the study or has completed one within 4 weeks prior to Day 1 dosing. 10. Subject has a hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any components of rifaximin ER and DER. 11. Subject is pregnant or a nursing woman. 12. Subject has a history of illicit drug use or abuse, either documented or in the opinion of the Investigator. 13. Subject is using any medication that is known to inhibit or induce CYP3A4, 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. 14. Subject 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). 15. Subject 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. 16. Subject has used bowel prep, laxative, or enema within 30 days prior to Day 1. 17. Subject has a 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. 18. Subject is planning to undergo a major surgical procedure during the duration of the study. 19. Subject has a positive test for human immunodeficiency virus (HIV)1 or HIV2. 20. Subject has an active Hepatitis B infection (HBsAg positive). Prior infection that is not active (i.e., HBsAg negative, HBcAb positive, and HBsAb positive) is permitted. 21. Subject has a positive test for Hepatitis C (HCV RNA). Prior infection with spontaneous resolution or sustained resolution for ≥ 24 weeks after cessation of antivirals is permitted. 22. Subject has an active COVID-19 infection or complication(s) related to COVID-19 infection that are unresolved or, in the opinion of the Investigator, may affect evaluation of the study drug or place the subject at undue risk. 23. Subjects has received a vaccine (including COVID-19 vaccine) within 2 weeks prior to Screening. If subject has received their first of two COVID-19 vaccination doses, as applicable, they must wait for at least 2 weeks after receiving the second dose, and be symptom-free, prior to beginning Screening. Subject must not be planning for COVID-19 or other vaccinations while on study. 24. Subject has a malignant disease. Exceptions include malignancies that were treated curatively and have not recurred within 2 years prior to study treatment, completely resected basal cell and squamous cell skin cancers, and any completely resected carcinoma in situ. 25. Subjects has prolonged QT interval as assessed by ECG history within the past 3 months. For subjects with no historical ECG information, subject has a resting QTcF ≥ 460 msec for males and ≥ 470 msec for females at Screening. 26. Subject has any unstable cardiac condition that, in the opinion of the Investigator, may worsen during the study or interfere with successful evaluation of the study treatment. 27. Subject has a serious mental or physical illness which, in the opinion of the Investigator, would compromise participation in the study. 28. Subject has any condition which, in the opinion of the Investigator, is likely to interfere with the successful collection of the measurements required for the study. 29. Subject is unable to understand or comply with study instructions and requirements.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Other
Trial scope: Specify scope
Pharmacokinetics, Pharmacodynamics
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
Yes, Lebanon and Worldwide
IMP has market authorization: Specify the countries
USA
Name of IMP
Rifaximin
Year of authorization
2004
Month of authorization
5
Type of IMP
Others
Type of IMP: Specify
Antibiotic
Pharmaceutical class
Non-aminoglycoside, semi-synthetic antibiotic derived from rifamycin that has antimicrobial activity of varying levels against Gram-positive, Gram-negative, aerobic, and anaerobic enteric bacteria.
Therapeutic indication
Sickle Cell Disease
Therapeutic benefit
Reduction of circulating aged neutrophils (CANs), significantly elevated during a VOC, in Sickle Cell Disease patients with history of VOCs
Biospecimen retention
None retained
Biospecimen description
N/A
Target sample size
9
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
01/12/2022
Date of study closure: Type
Anticipated
Date of study closure: Date
30/04/2023
Recruitment status
Pending
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
N/A
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
ClinicalTrials.gov
NCT05098028
Sources of Monetary or Material Support
Name
Bausch Health Americas, Inc.
Secondary Sponsors
Name
N/A
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Nadine
El Khoury
Beirut
Lebanon
+961 76 097 092
nadine.khoury@iqvia.com
IQVIA
Scientific
Sandra
Narain
400 Somerset Corporate Blvd. Bridgewater, NJ, 08807
United States of America
+1 908-242-8287
Sandra.Narain@bauschhealth.com
Salix Pharmaceuticals, Inc. a division of Bausch Health US, LLC
Scientific
Varsha
Bhatt
400 Somerset Corporate Blvd. Bridgewater, NJ, 08807
Uruguay
-
Varsha.Bhatt@bauschhealth.com
Salix Pharmaceuticals, Inc. a division of Bausch Health US, LLC
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Nini Hospital
Dr. Adlette Inati
Hematology
Approved
American University of Beirut Medical Center
Dr. Miguel Abboud
Hematology
Pending
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Nini Hospital
07/07/2022
Dr. Elias Bitar
-
+9616431400
Countries of Recruitment
Name
Lebanon
United States of America
Canada
Health Conditions or Problems Studied
Condition
Code
Keyword
Sickle Cell Disease
Sickle-cell disorders (D57)
Anemia, Hemolytic, Congenital, Hematologic Diseases,
Interventions
Intervention
Description
Keyword
Drug
Low Dose Rifaximin Extended Release Twice Daily
Rifaximin
Drug
Low Dose Rifaximin Delayed Extended Release Twice Daily
Rifaximin
Drug
High Dose Rifaximin Extended Release Twice Daily
Rifaximin
Drug
High Dose Rifaximin Delayed Extended Release Twice Daily
Rifaximin
Drug
Placebo Twice Daily
Placebo
Primary Outcomes
Name
Time points
Measure
Plasma concentration of rifaximin and 25-desacetyl rifaximin for PK profiles
Day 1 and Day 29
Blood samples for PK analysis
Cmax and Ctrough
Days 8, 15, and 29
Blood samples for PK analysis
PD biomarkers
Day 1, 8, 15, 29, 31, 43 and during medical facility visit for VOC, when possible
Collection of PD biomarkers (ANC, CANs, serum CD62L, hsCRP, the gut permeability biomarkers serum iFABP and LPS, and the gut bacteria biomarker urine 3-indoxyl sulfate)
Key Secondary Outcomes
Name
Time points
Measure
Safety
throughout the duration of the study
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Safety
throughout the duration of the study
Clinically significant changes from Baseline in clinical laboratory results (chemistry, coagulation, hematology, urinalysis, and high sensitivity C-reactive protein (hsCRP), physical examinations, and electrocardiograms (ECGs))
Safety
throughout the duration of the study
Changes from Baseline in vital signs (systolic and diastolic blood pressure, heart rate, oral body temperature, and oxygen saturation)
Safety
throughout the duration of the study
Information on any potential VOCs occurence
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial