Tuberculosis Clinical Trial
Official title:
Phase I Clinical Trial of the Pharmacokinetics of High-dose Daily Rifapentine, Given as a Single Dose or in Divided Doses to Healthy Volunteers
Verified date | October 2015 |
Source | National Institute of Allergy and Infectious Diseases (NIAID) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study will evaluate two different ways to give rifapentine (RPT), a drug that may help shorten treatment duration for tuberculosis (TB) disease.
Status | Completed |
Enrollment | 44 |
Est. completion date | June 2013 |
Est. primary completion date | June 2013 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: - Weight of 50 to 100 kg, inclusive - Absence of HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit within 21 days prior to study entry. NOTE: The term "licensed" refers to a U.S. FDA-approved kit. - Females of reproductive potential (defined as women who have not been postmenopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, and do not have documentation of having undergone a sterilization procedure [e.g., hysterectomy or bilateral oophorectomy or salpingectomy]) must have a negative serum or urine beta-human choriogonadotropin (ß-HCG) pregnancy test performed within 48 hours prior to entry. The urine test must have a sensitivity of at least 25 mlU/mL and be performed at a laboratory with Clinical Laboratory Improvement Amendment (CLIA) certification or its equivalent. - If participating in sexual activity that could lead to pregnancy, females must agree to use at least one reliable form of contraceptive while receiving the protocol-specified medications and for 1 week after stopping study medications. At least one (but preferably two) of the following contraceptives MUST be used appropriately: - Condoms (male or female) with or without a spermicidal agent - Diaphragm or cervical cap with spermicide - Intrauterine device (IUD) - NOTE: Hormone-based contraceptives are contraindicated with RPT and therefore may not be used as a form of contraception during this study. - Ability and willingness of volunteer to provide written informed consent - Laboratory values obtained within 21 days prior to entry: - Serum alanine aminotransferase (ALT) less than or equal to 1.2 times the upper limit of normal (ULN) - Total bilirubin level less than or equal to 1.2 times the ULN - Serum creatinine less than or equal to 1.5 mg/dL - Hemoglobin greater than or equal to 12.0 g/dL for men, greater than or equal to 11.0 g/dL for women - Platelet count greater than or equal to 125,000/mm^3 - Absolute neutrophil count greater than or equal to 1,250/mm^3 - Serum albumin greater than or equal to 3.5 g/dL - Hepatitis C antibody negative Exclusion Criteria: - Breastfeeding - Within 30 days prior to entry, use of any prescription medication known to inhibit or induce cytochrome P (CYP)3A metabolizing enzymes (refer to the manufacturers' package inserts for individual drugs). See list posted on the A5311 protocol-specific webpage (PSWP). - Known intolerance of or allergy to chicken eggs - Use of rifamycin antibiotics within 60 days prior to entry - Planned use during the study of prescription medications, herbal supplements, nutritional supplements, or over-the-counter medications except as follows: multivitamins, acetaminophen (up to 650 mg every 6 hours as an analgesic), ibuprofen (up to 600 mg twice daily), naproxen (up to 500 mg twice daily for pain or headache), and Benadryl (diphenhydramine, up to 25 mg daily for insomnia or seasonal allergies) are permitted. The use of topical or locally-acting drugs (e.g., eye drops, IUDs, skin ointments) will be considered on a case-by-case basis. - Within 14 days prior to study entry, hospitalization for any reason or pharmacotherapy for serious illness - Within 14 days prior to study entry, use of any prescription medication(s) - Receipt of any investigational study drug within 21 days prior to study entry - Known allergy/sensitivity or any hypersensitivity to rifamycins, including rifampin, rifabutin, and rifapentine - Presence of any condition interfering with normal gastrointestinal anatomy or motility that could interfere with drug absorption or excretion (including cholecystectomy, peptic ulceration, inflammatory bowel disease, or pancreatitis) - History or evidence of clinically significant (as determined by site investigator) cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s) - Any medical condition that, in the opinion of the site investigator, would interfere with the participant's ability to participate in the study - Active illicit drug use or dependence or alcohol dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements - History of TB infection or site investigator suspicion of current active TB - Inability to abstain from grapefruit and grapefruit juice for the duration of the study - Inability to adhere to the dietary requirements of the study (e.g., low-fat meal or boiled egg prior to drug doses during the study drug administration periods) |
Country | Name | City | State |
---|---|---|---|
United States | Johns Hopkins University CRS | Baltimore | Maryland |
United States | Chapel Hill CRS | Chapel Hill | North Carolina |
United States | Vanderbilt Therapeutics (VT) CRS | Nashville | Tennessee |
United States | UCSD Antiviral Research Center CRS | San Diego | California |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Benator D, Bhattacharya M, Bozeman L, Burman W, Cantazaro A, Chaisson R, Gordin F, Horsburgh CR, Horton J, Khan A, Lahart C, Metchock B, Pachucki C, Stanton L, Vernon A, Villarino ME, Wang YC, Weiner M, Weis S; Tuberculosis Trials Consortium. Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial. Lancet. 2002 Aug 17;360(9332):528-34. — View Citation
Zvada SP, Van Der Walt JS, Smith PJ, Fourie PB, Roscigno G, Mitchison D, Simonsson US, McIlleron HM. Effects of four different meal types on the population pharmacokinetics of single-dose rifapentine in healthy male volunteers. Antimicrob Agents Chemother. 2010 Aug;54(8):3390-4. doi: 10.1128/AAC.00345-10. Epub 2010 Jun 1. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | RPT PK parameter: area under the curve over 24 hours (AUC 0 to 24h) | Measured in Group 1, when given at a dose of 20 mg/kg once daily (Arm 1B) and when given at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Primary | RPT PK parameter: AUC 0 to 24h | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Primary | Grade 2 or higher signs and symptoms observed while on study beginning with the first dose of study drug and continuing through the follow-up period | Measured through Day 84 | ||
Secondary | RPT PK parameter: maximum observed plasma concentrations (Cmax) | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | Cmin (trough) values | Measured at Days 1, 7, 14, 43, 49, 56, 64, and 70 | ||
Secondary | Metabolizer status of human genetic variants/polymorphisms in gene SLCO1B1 and possibly other genes that are thought to affect PK of RIF | Measured at Day 0 | ||
Secondary | RPT PK parameter: minimum observed plasma concentration (Cmin) | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT PK parameter: oral clearance (CL/F) | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT PK parameter: elimination half-life (T 1/2) | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desacetyl-rifapentine (desRPT) PK parameter: AUC 0 to 24h | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: Cmax | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: Cmin | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: CL/F | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: T1/2 | Measured in Group 1, when RPT is given at a dose of 20 mg/kg once daily (Arm 1B) and at a dose of 10 mg/kg twice daily (Arm 1A) | Measured at Days 14 and 56 | |
Secondary | RPT PK parameter: Cmax | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT PK parameter: Cmin | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT PK parameter: CL/F | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT PK parameter: T1/2 | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: AUC 0 to 24h | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: Cmax | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: Cmin | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: CL/F | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT metabolite desRPT PK parameter: T1/2 | Measured in Group 2, when RPT is given at a dose of 15 mg/kg once daily with a boiled egg (Arm 2A) and at a dose of 15 mg/kg once daily with a low-fat meal (Arm 2B) | Measured at Days 14 and 56 | |
Secondary | RPT and its metabolite desRPT PK parameter AUC 0 to 24h at steady state when given at a dose of 20 mg/kg once daily (Group 1) and at a dose of 15 mg/kg once daily (Group 2 ) | Measured at Days 1, 14, 43, 56, and 70 | ||
Secondary | RPT and its metabolite desRPT PK parameter Cmax at steady state when given at a dose of 20 mg/kg once daily (Group 1) and at a dose of 15 mg/kg once daily (Group 2 ) | Measured at Days 1, 14, 43, 56, and 70 | ||
Secondary | RPT and its metabolite desRPT PK parameter Cmin at steady state when given at a dose of 20 mg/kg once daily (Group 1) and at a dose of 15 mg/kg once daily (Group 2 ) | Measured at Days 1, 14, 43, 56, and 70 | ||
Secondary | RPT and its metabolite desRPT PK parameter CL/F at steady state when given at a dose of 20 mg/kg once daily (Group 1) and at a dose of 15 mg/kg once daily (Group 2 ) | Measured at Days 1, 14, 43, 56, and 70 | ||
Secondary | RPT and its metabolite desRPT PK parameter T1/2 at steady state when given at a dose of 20 mg/kg once daily (Group 1) and at a dose of 15 mg/kg once daily (Group 2 ) | Measured at Days 1, 14, 43, 56, and 70 | ||
Secondary | RPT and its metabolite desRPT PK parameter area under the curve extrapolated to infinity (AUC 0 to inf) | Measured after single dose on Days 1 and 43 | ||
Secondary | RPT and its metabolite desRPT PK parameter CL/F | Measured after single dose on Days 1 and 43 | ||
Secondary | RPT and its metabolite desRPT PK parameter T1/2 | Measured after single dose on Days 1 and 43 | ||
Secondary | RPT and its metabolite desRPT PK parameter AUC 0 to 24h | Measured after multiple dose on Days 14 and 56 | ||
Secondary | RPT and its metabolite desRPT PK parameter CL/F | Measured after multiple dose on Days 14 and 56 | ||
Secondary | RPT and its metabolite desRPT PK parameter T1/2 | Measured after multiple dose on Days 14 and 56 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05738681 -
Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
|
Phase 2/Phase 3 | |
Recruiting |
NCT05526885 -
Tuberculosis Diagnostic Trial of CAD4TB Screening Alone Compared to CAD4TB Screening Combined With a CRP Triage Test, Both Followed by Confirmatory Xpert MTB/RIF Ultra in Communities of Lesotho and South Africa
|
N/A | |
Completed |
NCT04369326 -
Community Initiated Preventive Therapy for TB
|
N/A | |
Recruiting |
NCT04568967 -
TB-CAPT EXULTANT - HIV
|
N/A | |
Completed |
NCT02337270 -
Phase 1 Clinical Trial of the Safety and Immunogenicity of an Adenovirus-based TB Vaccine Administered by Aerosol
|
Phase 1 | |
Not yet recruiting |
NCT06253715 -
Shortened Regimen for Drug-susceptible TB in Children
|
Phase 3 | |
Recruiting |
NCT04271397 -
Immunological Biomarkers in Tuberculosis Management
|
N/A | |
Withdrawn |
NCT03639038 -
Tuberculosis Diagnosis by Flow Cytometry
|
||
Completed |
NCT03199313 -
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid
|
Phase 1 | |
Recruiting |
NCT04975178 -
Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa
|
Phase 3 | |
Completed |
NCT04463680 -
Rifampin and the Contraceptive Implant
|
Phase 4 | |
Completed |
NCT03973970 -
Assessing the Ability of the T-SPOT®.TB Test (IQ)
|
||
Recruiting |
NCT04230395 -
Alcohol Reduction Among People With TB and HIV in India
|
N/A | |
Completed |
NCT04874948 -
Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment
|
Phase 1 | |
Active, not recruiting |
NCT02906007 -
Evaluating the Pharmacokinetics, Safety, and Tolerability of Bedaquiline in Infants, Children, and Adolescents With Multidrug-Resistant Tuberculosis, Living With or Without HIV
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT05917210 -
Peer-led Implementation of TB-HIV Education and Adherence Counseling in Uganda
|
N/A | |
Not yet recruiting |
NCT06017843 -
Impact Evaluation of Use of MATCH AI Predictive Modelling for Identification of Hotspots for TB Active Case Finding
|
N/A | |
Not yet recruiting |
NCT05845112 -
Start Taking Action For TB Diagnosis
|
||
Active, not recruiting |
NCT02715271 -
Study of TB Lesions Obtained in Therapeutical Surgery
|
||
Completed |
NCT02781909 -
Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis
|
Phase 2 |