Evaluating the Safety and Drug Interaction of PA-824, an Investigational Tuberculosis Medication, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin

Tuberculosis Clinical Trial

Official title: A Phase I, Three-Arm Safety, Tolerability, and Pharmacokinetic Interaction Study of PA-824, an Investigational Nitroimidazole for the Treatment of Tuberculosis, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin

Status Completed

Clinical Trial Summary

Tuberculosis (TB) is a global public health concern and developing new treatment regimens is an important research priority. PA-824 is an experimental TB medication. This study will evaluate the safety and tolerability of PA-824 when combined with efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r), which are medications used to treat HIV infection, or rifampin (RIF), which is a medication used to treat TB. Study researchers will examine the safety and tolerability of these drug combinations and how the medications affect the levels of PA-824 in the blood.

Clinical Trial Description

TB is a global public health threat. In 2009, there were an estimated 9.4 million cases of TB and 1.8 million deaths from the disease. TB treatment regimens are often lengthy and complex, and multidrug-resistant (MDR) TB is emerging as a worldwide epidemic. TB is also one of the most common causes of death among people infected with HIV. PA-824 is an experimental drug developed for the treatment of TB. This study will evaluate the safety, tolerability, and pharmacokinetic (PK) drug interactions between PA-824 and EFV, LPV/r, or RIF. This study will enroll healthy adults who are not infected with HIV or TB. Participants will be enrolled into one of three arms, with Arms 1 and 2 each consisting of two groups. Participants in Arm 1 will be randomly assigned to receive PA-824 alone or EFV alone followed by EFV plus PA-824 in one of two sequences. Participants in Arm 2 will be randomly assigned to receive PA-824 alone or LPV/r alone followed by LPV/r plus PA-824 in one of two sequences. For participants in Arms 1 and 2, there will be a 14-day washout period between treatments, where participants will not receive any medication. Participants in Arm 3 will receive PA-824 alone, followed by RIF alone, and then RIF plus PA-824. Participants in Arms 1 and 2 will attend outpatient study visits at study entry and either Days 3, 22, and 29 or Days 7, 36, and 39, depending on which group they are in. Participants in Arm 3 will attend outpatient study visits at study entry and Days 3, 10, and 15. At most study visits, participants will undergo a physical examination, vital sign measurements, medication and medical history review, and blood collection. Participants will complete a medication and symptom diary throughout the study. All participants also will be admitted to an inpatient clinical research unit two or three times during the study, depending on which arm they are enrolled in. Each inpatient visit will last 1 or 2 days. During the inpatient visits, participants will undergo several blood collections throughout the day; select visits also will include an electrocardiogram (ECG). Participants in Arms 1 and 2 will receive the last dose of their assigned medication on Day 42. Participants in Arm 3 will receive the last dose of their assigned medication on Day 21. A final study visit will occur for all participants 1 to 2 weeks later. ;

Related Conditions & MeSH terms

• Tuberculosis

• NCT number: NCT01571414
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Completed
• Phase: Phase 1
• Start date: May 2012
• Completion date: May 2013