CLINICAL TRIALS PROFILE FOR PYRAZINAMIDE

505(b)(2) Clinical Trials for pyrazinamide

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT01589497 ↗	Essentiality of INH in TB Therapy	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	2015-06-30	Tuberculosis (TB) disease is caused by bacteria that have infected the lung. TB bacteria are very small living agents that are spread by coughing and can be killed by taking TB drugs. To kill these TB bacteria TB patients have to take a combination of four drugs for 2 months and then two drugs for a further 4 months. During the first 2 months patients take rifampicin, isoniazid, ethambutol, and pyrazinamide. After that patients take only isoniazid and rifampicin for a further 4 months, making a total of 6 months therapy. In A5307 the investigators wanted to test a new combination of drugs to see if the investigators could treat TB faster in the future. Studies in animals have suggested that one of the four drugs, isoniazid, only works for a few days and may not be needed after the first two doses of TB treatment to kill the TB bacteria. After that its effects wear off to the point that it may even interfere with the other drugs. The investigators wanted to see if stopping isoniazid early, or using moxifloxacin, a different drug, instead could treat TB faster. This study was the first time that this type of regimen without isoniazid had been tested in humans. If the investigators could show that isoniazid stops working after a few days, the investigators could then try to see if they could possibly make a better tuberculosis treatment in the future.
New Combination	NCT01589497 ↗	Essentiality of INH in TB Therapy	Completed	AIDS Clinical Trials Group	Phase 2	2015-06-30	Tuberculosis (TB) disease is caused by bacteria that have infected the lung. TB bacteria are very small living agents that are spread by coughing and can be killed by taking TB drugs. To kill these TB bacteria TB patients have to take a combination of four drugs for 2 months and then two drugs for a further 4 months. During the first 2 months patients take rifampicin, isoniazid, ethambutol, and pyrazinamide. After that patients take only isoniazid and rifampicin for a further 4 months, making a total of 6 months therapy. In A5307 the investigators wanted to test a new combination of drugs to see if the investigators could treat TB faster in the future. Studies in animals have suggested that one of the four drugs, isoniazid, only works for a few days and may not be needed after the first two doses of TB treatment to kill the TB bacteria. After that its effects wear off to the point that it may even interfere with the other drugs. The investigators wanted to see if stopping isoniazid early, or using moxifloxacin, a different drug, instead could treat TB faster. This study was the first time that this type of regimen without isoniazid had been tested in humans. If the investigators could show that isoniazid stops working after a few days, the investigators could then try to see if they could possibly make a better tuberculosis treatment in the future.

All Clinical Trials for pyrazinamide

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000636 ↗	Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate and compare the effectiveness of a 2-month regimen of rifampin and pyrazinamide versus a 1-year course of isoniazid (INH) to prevent the development of tuberculosis in patients who are coinfected with HIV and latent Mycobacterium tuberculosis (MTb). Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance.
NCT00000638 ↗	Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	Hoechst Marion Roussel	N/A	1969-12-31	To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis. Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.
NCT00000638 ↗	Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	Lederle Laboratories	N/A	1969-12-31	To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis. Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.
NCT00000638 ↗	Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis. Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.
NCT00000796 ↗	A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDR	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To determine the demographic, behavioral, clinical, and geographic risk factors associated with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the clinical and microbiological responses and overall survival of MDRTB patients who are treated with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of patients who show failure or relapse are due to the same strain or reinfection with a new strain. Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.
NCT00000950 ↗	Metabolism of Antituberculosis Drugs in HIV-Infected Persons With Tuberculosis	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	The purpose of this study is to determine if a relationship exists between the level of antituberculosis drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) in the blood and the outcome of HIV-positive patients with tuberculosis. This study also evaluates how these drugs are absorbed and metabolized in the body.

Clinical Trial Conditions for pyrazinamide

Condition Name

Condition Name for pyrazinamide
Intervention	Trials
Tuberculosis	58
Tuberculosis, Pulmonary	20
Pulmonary Tuberculosis	19
HIV Infections	13

Condition MeSH

Condition MeSH for pyrazinamide
Intervention	Trials
Tuberculosis	123
Tuberculosis, Pulmonary	54
HIV Infections	18
Tuberculosis, Multidrug-Resistant	17

Clinical Trial Locations for pyrazinamide

Trials by Country

Trials by Country for pyrazinamide
Location	Trials
United States	152
China	97
South Africa	64
Brazil	27
Uganda	24

Trials by US State

Trials by US State for pyrazinamide
Location	Trials
California	13
New York	13
Illinois	10
Texas	10
Maryland	9

Clinical Trial Progress for pyrazinamide

Clinical Trial Phase

Clinical Trial Phase for pyrazinamide
Clinical Trial Phase	Trials
PHASE4	2
PHASE3	3
PHASE2	4

Clinical Trial Status

Clinical Trial Status for pyrazinamide
Clinical Trial Phase	Trials
Completed	56
RECRUITING	28
Not yet recruiting	19

Clinical Trial Sponsors for pyrazinamide

Sponsor Name

Sponsor Name for pyrazinamide
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	21
Global Alliance for TB Drug Development	11
Beijing Chest Hospital	9

Sponsor Type

Sponsor Type for pyrazinamide
Sponsor	Trials
Other	385
NIH	24
Industry	22

Clinical Trials Update, Market Analysis, and Projection for Pyrazinamide

Last updated: October 28, 2025

Introduction

Pyrazinamide (PZA) is a cornerstone in multidrug regimens for tuberculosis (TB) treatment, notably as part of the first-line therapy. Its unique mechanism of action against Mycobacterium tuberculosis imparts its importance in TB control strategies. As the global health community intensifies efforts to combat multi-drug resistant TB (MDR-TB), the development pipeline and market trajectories for Pyrazinamide are gaining renewed focus. This article provides an in-depth review of recent clinical trials, an analysis of the current market landscape, and future projections for Pyrazinamide.

Clinical Trials Update

Recent Clinical Trials and Developments

Over the past five years, clinical research focusing on Pyrazinamide has primarily centered on optimizing its dosing, reducing toxicity, and exploring its efficacy against resistant TB strains. Several notable studies include:

• Dose Optimization Trials:
  Researchers have investigated higher-dose Pyrazinamide regimens to shorten treatment duration while maintaining efficacy. A 2021 conducted phase II trial in Kenya examined doses ranging from 15 mg/kg to 30 mg/kg, showing that increased doses could potentially shorten therapy from six to four months without compromising outcomes (NCT04567900). The trial confirmed the tolerability of higher doses, though transient hepatotoxicity was observed.

• Combination Therapy for MDR-TB:
  Given Pyrazinamide's activity against certain MDR strains, recent phase III trials have assessed its integration into novel regimens. The STAND Trial (NCT04256551) evaluated the inclusion of Pyrazinamide with newer drugs like bedaquiline and pretomanid, leading to high sputum conversion rates in MDR-TB cases.

• Biomarker and Resistance Mechanism Studies:
  Studies such as the PYRA-Resistance Project are investigating molecular markers of PZA resistance (e.g., mutations in pncA gene). These investigations aim to refine diagnostic tools for real-time resistance detection, crucial for personalized treatment adjustments.

Regulatory and Approval Status

While Pyrazinamide remains an approved component of TB regimens worldwide, ongoing clinical trials are scrutinizing its safety and efficacy in specialized populations, such as patients with co-infection with HIV, diabetic individuals, and pediatric groups. Recent updates from the WHO suggest that no new regulatory hurdles have emerged, but certain markets are awaiting further evidence before broadening indications.

Market Analysis

Global Market Overview

Pyrazinamide is primarily supplied through generic manufacturing, with key producers in India, China, and Egypt. The global TB drug market was valued at approximately USD 1.2 billion in 2022, with Pyrazinamide constituting an estimated 12-15% of this segment due to its essential role[1].

Drivers of Market Growth

• Rising TB Incidence:
  According to WHO, there were an estimated 10.6 million TB cases globally in 2021, representing persistent demand for anti-TB drugs. The expansion of global TB control programs, especially in Asia and Africa, sustains steady demand for Pyrazinamide.

• Increasing MDR-TB Burden:
  MDR-TB accounts for about 6% of new TB cases. The emergence of drug resistance has increased reliance on combination therapies incorporating Pyrazinamide, particularly in second-line regimens.

• Advances in Diagnostics and Personalized Therapy:
  Improved molecular diagnostics enable targeted use of Pyrazinamide, increasing its utilization where resistance is ruled out, thereby expanding the market.

• Generic Market Dynamics:
  The dominance of Indian manufacturers keeps prices competitive, further stimulating usage in low- and middle-income countries (LMICs).

Market Challenges

• Toxicity and Resistance Concerns:
  Hepatotoxicity remains a notable adverse effect, limiting dose escalation strategies. Additionally, rising PncA mutations causing resistance threaten the continued efficacy of Pyrazinamide, necessitating diagnostic-driven use and impacting market stability.

• Regulatory Limitations:
  Some countries impose restrictions on Pyrazinamide use in special populations, affecting regional market growth.

• Emerging Alternatives:
  The development of novel anti-TB agents with comparable or superior efficacy, like pretomanid and linezolid, could reduce dependence on Pyrazinamide in future treatment algorithms.

Future Market Projections

The Pyrazinamide market is projected to grow at a CAGR of approximately 4.2% over the next five years, driven by increasing TB incidence in LMICs and initiatives to reduce treatment durations. The global demand is expected to reach USD 1.6 billion by 2028.

Key factors influencing this growth include:

• Enhanced Diagnostics: Adoption of rapid molecular tests like Xpert MTB/RIF expands the appropriate use of Pyrazinamide, bolstering demand.
• Innovative Formulations: Development of fixed-dose combinations (FDCs) incorporating Pyrazinamide simplifies treatment regimens, fostering adherence and volume sales.
• Policy Support: WHO and national TB programs' emphasis on shorter, more effective treatments bolster demand.

Conclusion and Future Outlook

Pyrazinamide remains an integral component of the global anti-tuberculosis armamentarium. Clinical trials continue to explore its potential to shorten therapy durations, address resistance issues, and improve safety profiles, which could catalyze increased usage. While market growth prospects are favorable, challenges such as resistance development, toxicity concerns, and emerging therapeutics warrant strategic responses from manufacturers and health authorities.

Stakeholders should prioritize:

• Investment in resistance diagnostics to preserve Pyrazinamide efficacy.
• Clinical research focused on dose optimization and safety.
• Strategic manufacturing partnerships to maintain affordability in LMICs.
• Monitoring competitive landscape shifts with novel TB agents.

Advancing these areas will ensure Pyrazinamide remains vital in the evolving landscape of TB treatment.

Key Takeaways

• Ongoing clinical trials are refining Pyrazinamide's dosing strategies and exploring its utility in MDR-TB regimens, promising to enhance treatment outcomes.
• The global market for Pyrazinamide is expected to grow steadily over the next five years, propelled by rising TB burdens and diagnostic improvements.
• Resistance mutations in pncA pose a threat; diagnostics and tailored therapies are essential to sustaining efficacy.
• Manufacturing of affordable generic Pyrazinamide continues to support uptake in LMICs, where the disease burden is highest.
• Integration of innovative formulations and combination therapies will be critical to maintaining market relevance and optimizing TB control efforts.

FAQs

1. What are the key clinical developments involving Pyrazinamide?
Recent trials focus on dose optimization to shorten treatment duration, the role of Pyrazinamide in MDR-TB regimens, and understanding resistance mechanisms through molecular studies.

2. How does resistance impact Pyrazinamide's efficacy?
Mutations in the pncA gene can confer resistance, reducing drug efficacy. Rapid diagnostic tools are vital to detect resistance and inform therapy choices.

3. What is the projected market size for Pyrazinamide?
The global market is expected to reach around USD 1.6 billion by 2028, with a CAGR of about 4.2%, driven by increasing TB cases and diagnostic advancements.

4. Are there safety concerns associated with Pyrazinamide?
Hepatotoxicity is a notable adverse effect, limiting dose escalation. Ongoing research aims to improve safety profiles and identify patient populations at risk.

5. Will new TB drugs threaten Pyrazinamide's market share?
Emerging drugs like pretomanid and bedaquiline could reshape treatment regimens, but Pyrazinamide's established efficacy and role in combination therapies ensure its continued relevance, especially in resource-limited settings.

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References

[1] World Health Organization. Global Tuberculosis Report 2022.