Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers

2014-08-27 03:18:47 | BioPortfolio


Common treatments for tuberculosis (TB) can interfere with certain antiretroviral (ARV) medications used to treat HIV. People whose immune systems are weakened by HIV infection are susceptible to TB, so it is important to find treatments for both that can be given in combination. This study will test the safety of combining a new medication for TB with an already approved HIV medication in healthy adults.


Tuberculosis (TB) is the second most deadly infectious disease after HIV. Multidrug-resistant TB (MDR-TB) has emerged as a worldwide epidemic, limiting treatment options. HIV infected people with suppressed immune systems are particularly susceptible to TB, and TB is the leading cause of death among people with HIV. Treating people infected with both HIV and TB is particularly problematic because rifamycins, the drug class usually used to treat TB, lower the effectiveness of certain anti-HIV medications. Studies of pharmacokinetics (PK), the interactions between drugs and body, are needed to determine which anti-TB and anti-HIV medications can be safely and effectively combined. This study will examine TMC207, a new anti-TB medication with the potential to shorten TB treatment time, combined with efavirenz (EFV), an antiretroviral (ARV) medication used in many first-line treatment regimens for HIV. The study will test PK and safety of this combination in healthy volunteers.

Participation in this study will last 49 days. At entry, participants will complete basic assessments, including taking a medical history and completing a physical exam, an eye exam, an electrocardiogram (ECG) to measure heartbeat, a pregnancy test, and a blood test. Certain behaviors and substances will be prohibited during the study, including consuming grapefruit, alcohol, or caffeine (on PK visit days); taking nutritional supplements, over-the-counter herbal medicines, and certain medicines and drugs from other studies; and excessive smoking. Participants will also be asked to keep a medication diary to record all medications they take during the study.

All participants will receive study medications on the same schedule: a single dose of TMC207 on Days 1 and 29, and daily dosing of EFV on Days 15 to 43.

Participants will complete two PK visits, one from Days 1 to 3, and one from Days 28 to 31. During PK visits, participants will have their vital signs checked and undergo an ECG, and they may also complete a limited physical exam, give a medication history, and report on symptoms. They will have multiple blood samples taken via a catheter left in place for the 3-day visit. Blood samples will be taken before receiving TMC207; 1, 2, 3, 4, 5, 6, 8, and 12 hours after receiving TMC207; and again on the mornings of Days 2 and 3.

Participants will complete six outpatient visits over the 11 days following each PK visit and one outpatient visit on Day 21, between PK visits. At outpatient visits participants will complete a blood draw and may complete a limited physical exam and medical history, record symptoms, and review their medication diaries.

On Day 49 participants will complete their last study visit, repeating many of the assessments from baseline testing. In the case of side effects or abnormal blood tests, participants may be monitored longer for safety reasons.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment




Efavirenz (EFV), TMC207


Johns Hopkins Adult AIDS CRS
United States




National Institute of Allergy and Infectious Diseases (NIAID)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:18:47-0400

Clinical Trials [507 Associated Clinical Trials listed on BioPortfolio]

TMC207-C202: Study to Evaluate Bactericidal Activity of Multiple Oral Doses of TMC207 in Subjects With Sputum-Smear Positive Tuberculosis

The purpose of this study is to assess the effects of 3 different oral doses of TMC207 administered over a 7 day period on the organism that causes tuberculosis

TMC207-TiDP13-C111: Trial With Healthy Volunteers to Determine the Levels of TMC207 in Blood After a Single Orale Dose of TMC207

The purpose of this study is to evaluate the levels of TMC207 and its active metabolite (degradation product) called M2 in the blood circulation of healthy volunteers after oral administra...

TMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Patients With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).

The objective of this study is to demonstrate that the antibacterial activity of TMC207 is better than placebo when added to a standardized Background Regimen (BR) for treatment of multi-d...

TMC207-TiDP13-C110: Interaction Study With Lopinavir/Ritonavir in Healthy Volunteer

The purpose of this Phase I, open-label, randomized crossover trial is to investigate the pharmacokinetic interaction between steady-state lopinavir/ritonavir and single-dose TMC207 in hea...

Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB co-Infected Patients (ANRS 12146 CARINEMO)

The purpose of this study is to determine whether the use of Nevirapine in HIV patients already treated against tuberculosis by Rifampicin is as efficient and as well tolerated as Efaviren...

PubMed Articles [938 Associated PubMed Articles listed on BioPortfolio]

The Use of Efavirenz During Pregnancy is Associated with Suicidal Ideation in Postpartum Women in Rural South Africa.

Efavirenz is used for the management of HIV infection during pregnancy in South Africa (SA), but it is contraindicated in patients with history of depression due to possible suicidal ideation. This st...

Anatomic and Cellular Niches for Mycobacterium tuberculosis in Latent Tuberculosis Infection.

Latent tuberculosis has been recognized for over a century, but discovery of new niches, where Mycobacterium tuberculosis resides, continues. We evaluated literature on M.tuberculosis locations during...

Extended cell and plasma drug levels after one dose of a 3-in-1 nanosuspension containing lopinavir, efavirenz, and tenofovir in non-human primates.

To characterize a drug-combination nanoparticle (DcNP) containing water-insoluble lopinavir (LPV) and efavirenz (EFV), and water-soluble tenofovir (TFV), for its potential as a long-acting combination...

Latent tuberculosis infection and tuberculosis in children and adolescents.

To describe the characteristics of patients diagnosed with tuberculosis and latent tuberculosis infection.

Novel M. tuberculosis specific IL-2 ELISpot assay discriminates adult patients with active or latent tuberculosis.

Tuberculosis (TB) still is a major worldwide health problem, with 10.4 million new cases in 2016. Only 5-15% of people infected with M. tuberculosis develop TB disease while others remain latently inf...

Medical and Biotech [MESH] Definitions

The dormant form of TUBERCULOSIS where the person shows no obvious symptoms and no sign of the causative agent (Mycobacterium tuberculosis) in the SPUTUM despite being positive for tuberculosis infection skin test.

Tuberculosis of the brain, spinal cord, or meninges (TUBERCULOSIS, MENINGEAL), most often caused by MYCOBACTERIUM TUBERCULOSIS and rarely by MYCOBACTERIUM BOVIS. The infection may be limited to the nervous system or coexist in other organs (e.g., TUBERCULOSIS, PULMONARY). The organism tends to seed the meninges causing a diffuse meningitis and leads to the formation of TUBERCULOMA, which may occur within the brain, spinal cord, or perimeningeal spaces. Tuberculous involvement of the vertebral column (TUBERCULOSIS, SPINAL) may result in nerve root or spinal cord compression. (From Adams et al., Principles of Neurology, 6th ed, pp717-20)

Pathological conditions of the CARDIOVASCULAR SYSTEM caused by infection of MYCOBACTERIUM TUBERCULOSIS. Tuberculosis involvement may include the HEART; the BLOOD VESSELS; or the PERICARDIUM.

TUBERCULOSIS that involves any region of the GASTROINTESTINAL TRACT, mostly in the distal ILEUM and the CECUM. In most cases, MYCOBACTERIUM TUBERCULOSIS is the pathogen. Clinical features include ABDOMINAL PAIN; FEVER; and palpable mass in the ileocecal area.

Tuberculosis of the mouth, tongue, and salivary glands.

More From BioPortfolio on "Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers"

Quick Search


Relevant Topics

Tuberculosis TB
Tuberculosis (TB) is an infectious disease caused by bacteria belonging to the Mycobacterium tuberculosis complex. Over nine million new cases of TB, and nearly two million deaths from TB, are estimated to occur around the world every year, and new inf...

AIDS; Acquired Immune Deficiency Syndrome. HIV; Human Immunodeficiency Virus HIV infection causes AIDS. HIV infection also causes the production of anti-HIV antibodies, which forms the test for HIV in patients. People who have the HIV antibodies are ...

Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...

Searches Linking to this Trial