Evaluating the Pharmacokinetics of High-Dose Rifapentine When Given as a Single Dose or in Divided Doses to Healthy Adults

• Status: Completed
• Trial end date: 2013-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will evaluate two different ways to give rifapentine (RPT), a drug that may help shorten treatment duration for tuberculosis (TB) disease.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Rifampin; Rifapentine

Criteria

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 (β-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)