# Safety and tolerability of new and repurposed drugs for MDR-TB treatment

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $196,727

## Abstract

Project Summary/Abstract
The candidate, Gustavo E. Velasquez, MD, MPH, is an infectious disease physician at Brigham and Women’s
Hospital and an instructor at Harvard Medical School. This K08 career development award will prepare the
candidate for an independent investigative career in tuberculosis clinical trials research. Dr. Velasquez’s career
goal is to establish himself as a clinical trialist with specific expertise in the evaluation of drug toxicity in
complex multidrug regimens for the treatment of tuberculosis. Dr. Velasquez proposes a five-year program
during which he will conduct clinical research that enhances our understanding of the safety and tolerability of
new and repurposed drugs to treat multidrug-resistant tuberculosis (MDR-TB), using observational,
experimental, and pharmacokinetic data. Dr. Velasquez will engage in an intensive mentored research
experience with [1] Carole D. Mitnick, ScD, a tuberculosis epidemiologist and an international expert in
tuberculosis clinical trials whose career has been dedicated to optimizing treatment for tuberculosis; [2]
professor Helen M. McIlleron, MBChB, PhD, a clinical pharmacologist and an international expert in
antituberculous and antiretroviral drug pharmacometrics; and [3] professor Daniel R. Kuritzkes, MD, an
internationally recognized expert in HIV antiretroviral therapy. Two new drugs, bedaquiline and delamanid, and
two repurposed drugs, clofazimine and linezolid, were recently recommended for MDR-TB treatment. A
growing body of data is emerging from clinical trials of novel MDR-TB regimens using these drugs, yet high-
quality evidence on their safety and tolerability—informed by pharmacokinetics—is sorely lacking. Dr.
Velasquez will leverage his unique access to existing and forthcoming data from four clinical trials and two
observational studies of tuberculosis patients to address this problem. He will [1] examine the safety and
tolerability of bedaquiline and delamanid within conventional MDR-TB regimens; [2] estimate the effect of
linezolid-dose reduction strategies on the safety and tolerability of MDR-TB treatment and the
pharmacokinetics of linezolid; and [3] estimate the effect of plasma drug exposure on the safety and tolerability
of combinations of new and repurposed drugs in a Phase III trial. His proposal strives to transform the
evidence base for clinical decision-making around averting and managing toxicity during MDR-TB treatment.
This project will apply novel methods to rich and rigorously collected datasets to develop an understanding of
the relationship between combination regimens for MDR-TB, plasma concentration of the drugs, and
treatment-emergent toxicity. The Division of Infectious Diseases at Brigham and Women’s Hospital and the
Department of Global Health and Social Medicine at Harvard Medical School are an ideal setting to conduct
the candidate’s proposed activities, due to the breadth and scope of multi-disciplinary collaborations in the
control of tuberc...

## Key facts

- **NIH application ID:** 9858265
- **Project number:** 5K08AI141740-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Gustavo Eduardo Velasquez
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,727
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858265

## Citation

> US National Institutes of Health, RePORTER application 9858265, Safety and tolerability of new and repurposed drugs for MDR-TB treatment (5K08AI141740-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858265. Licensed CC0.

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