CLINICAL TRIALS PROFILE FOR PRETOMANID

All Clinical Trials for Pretomanid

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00042289 ↗	Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)		2003-03-01	The purpose of this study is to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study will also evaluate the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs will be evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.
NCT00042289 ↗	Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy	Completed	National Institute of Allergy and Infectious Diseases (NIAID)		2003-03-01	The purpose of this study is to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study will also evaluate the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs will be evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.
NCT02256696 ↗	Assessing PA-824 for Tuberculosis (the APT Trial)	Recruiting	University of Cape Town	Phase 2	2015-04-29	Assess the mycobactericidal activity of PA-824 (given at 200 mg daily) when added to first-line tuberculosis (TB) treatment (isoniazid, pyrazinamide, and a rifamycin antibiotic) over 12 weeks of treatment. Funding Source - FDA OOPD
NCT02256696 ↗	Assessing PA-824 for Tuberculosis (the APT Trial)	Recruiting	Johns Hopkins University	Phase 2	2015-04-29	Assess the mycobactericidal activity of PA-824 (given at 200 mg daily) when added to first-line tuberculosis (TB) treatment (isoniazid, pyrazinamide, and a rifamycin antibiotic) over 12 weeks of treatment. Funding Source - FDA OOPD
NCT02333799 ↗	A Phase 3 Study Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Drug Resistant Pulmonary Tuberculosis	Completed	Global Alliance for TB Drug Development	Phase 3	2015-03-01	The purpose of this study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of bedaquiline plus PA-824 plus linezolid after 6 months of treatment (option for 9 months for subjects who remain culture positive at month 4) in Subjects with either pulmonary extensively drug resistant tuberculosis (XDR-TB), treatment intolerant or non-responsive multi-drug resistant tuberculosis (MDR-TB).
NCT02422524 ↗	Pretomanid in Adults With Hepatic Impairment	Recruiting	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	2017-12-11	This is a Phase 1, single dose (200 mg), open-label, sequential group study comparing the pharmacokinetics and safety of Pretomanid in subjects with mild, moderate, and severe hepatic impairment to matched, non-hepatically impaired subjects. There will be approximately 36 total subjects, adult males and females, 18 to 70 years of age, inclusive. The study will be conducted at 2 sites, study duration is approximately 24 months, and subject participation duration is approximately 5 weeks (including screening). Primary objective: To evaluate the pharmacokinetics of a single oral dose of Pretomanid in subjects with mild, moderate, and severe hepatic impairment (as assessed by Child-Pugh score), relative to matched non-hepatically impaired subjects. Secondary objective: To evaluate the safety of a single oral dose of Pretomanid in subjects with mild, moderate, and severe hepatic impairment (as assessed by Child-Pugh score), relative to matched non-hepatically impaired subjects.

Clinical Trial Conditions for Pretomanid

Condition Name

Condition Name for Pretomanid
Intervention	Trials
Tuberculosis	7
Pulmonary Tuberculosis	7
Tuberculosis, Multidrug-Resistant	4
Tuberculosis, Pulmonary	4

Condition MeSH

Condition MeSH for Pretomanid
Intervention	Trials
Tuberculosis	18
Tuberculosis, Pulmonary	13
Tuberculosis, Multidrug-Resistant	9
Extensively Drug-Resistant Tuberculosis	6

Clinical Trial Locations for Pretomanid

Trials by Country

Trials by Country for Pretomanid
Location	Trials
South Africa	31
United States	24
Thailand	6
Uzbekistan	6
Brazil	6

Trials by US State

Trials by US State for Pretomanid
Location	Trials
Missouri	3
Texas	2
North Carolina	2
Maryland	1
Louisiana	1

Clinical Trial Progress for Pretomanid

Clinical Trial Phase

Clinical Trial Phase for Pretomanid
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	3
Phase 2/Phase 3	6

Clinical Trial Status

Clinical Trial Status for Pretomanid
Clinical Trial Phase	Trials
Recruiting	10
Active, not recruiting	4
Not yet recruiting	4

Clinical Trial Sponsors for Pretomanid

Sponsor Name

Sponsor Name for Pretomanid
Sponsor	Trials
Global Alliance for TB Drug Development	10
National Institute of Allergy and Infectious Diseases (NIAID)	5
Wits Health Consortium (Pty) Ltd	5

Sponsor Type

Sponsor Type for Pretomanid
Sponsor	Trials
Other	129
NIH	8
Industry	8

Pretomanid: A Breakthrough in Tuberculosis Treatment

Introduction to Pretomanid

Pretomanid, a novel antibiotic, has been a significant advancement in the treatment of tuberculosis (TB), particularly for patients with drug-resistant forms of the disease. Developed by the TB Alliance, pretomanid has undergone extensive clinical trials and has shown promising results.

Clinical Trials Overview

Trial Design and Participants

Pretomanid was evaluated in a single, uncontrolled, multicenter trial that enrolled 109 adult patients with either pulmonary extensively drug-resistant tuberculosis (XDR-TB) or treatment-intolerant/nonresponsive multidrug-resistant tuberculosis (TI/NR MDR-TB)[1][4].

• The trial was conducted at three sites in South Africa and included patients aged 17-60 years.
• All patients received pretomanid as part of a three-drug combination regimen with bedaquiline and linezolid, taken orally once daily for six months[1].

Efficacy Results

The primary endpoint of the trial was treatment failure, defined as the incidence of bacteriologic failure, bacteriologic relapse, or clinical failure six months after the end of treatment.

• The trial showed that 95 out of 107 patients (89%) had no TB bacteria in the sputum six months after completing the treatment, indicating a high efficacy rate[1][4].

Demographics of Trial Participants

The demographics of the safety population in the trial were as follows:

• Sex: 57 men (52.3%) and 52 women (47.7%)[1].
• Race: 83 Black (76.1%), 25 Mixed (22.9%), and 1 White (0.9%)[1].
• Age Group: 34 patients were under 30 years old, and 75 were over 30 years old[1].

Ongoing and Future Clinical Trials

PAN-TB Collaboration

The Project to Accelerate New Treatments for Tuberculosis (PAN-TB) collaboration has launched a phase 2b/c clinical trial to evaluate two novel drug regimens that include pretomanid, along with bedaquiline, delamanid, quabodepistat, and sutezolid. This trial aims to identify a candidate regimen capable of treating all forms of active pulmonary TB, including drug-sensitive TB (DS-TB), with shorter treatment durations and without the need for accompanying drug-resistance testing[3].

ZeNix and Nix-TB Trials

• The ZeNix trial has demonstrated the maintained efficacy of the BPaL regimen (bedaquiline, pretomanid, and linezolid) with reduced dosing of linezolid, further optimizing the treatment[4].
• The Nix-TB trial, which has been presented at several conferences, has shown that the BPaL regimen cured 89% of the first 75 XDR-TB patients after six months of treatment and six months of post-treatment follow-up[4].

Market Analysis and Projections

Global TB Drugs Market

The global tuberculosis drugs market is expected to grow significantly due to several factors:

• Rising Prevalence of MDR-TB: The increasing incidence of multidrug-resistant tuberculosis and HIV-TB co-infection is driving the market growth[5].
• Development of New Treatments: The development of shorter-regimen drug treatments, such as the combination of pretomanid, linezolid, and bedaquiline, is expected to boost the market[5].

Market Size and Growth

• The global TB drugs market is projected to reach USD 1.38 billion by 2025, growing at a CAGR of 5.2% during the forecast period[5].

Pricing and Access

• There is a strong consensus on the need for affordable pricing for TB drugs. For pretomanid, a medium-term target price of $130 has been suggested, although issues with market entry and supply chain complexities need to be addressed[2].
• Efforts by organizations like the TB Alliance and the Stop TB Partnership are focused on ensuring access to these drugs, including working with manufacturers to optimize pricing and supply chain management[2].

Regulatory Approvals

FDA Approval

Pretomanid was approved by the U.S. Food and Drug Administration (FDA) under the Limited Population Pathway for Antibacterial and Antifungal Drugs, which allows for the approval of antibacterial and antifungal drugs to treat serious or life-threatening infections in a limited population of patients with unmet need[1].

WHO Prequalification and Other Approvals

• Pretomanid has been listed by the World Health Organization (WHO) as a Prequalified Medicinal Product.
• It has received EU marketing authorization in combination with bedaquiline and linezolid for treating highly drug-resistant TB.
• Pretomanid also received approval from the Drug Controller General of India (DCGI) for conditional access under the National Tuberculosis Elimination Program (NTEP)[4].

Key Takeaways

• High Efficacy: Pretomanid, in combination with bedaquiline and linezolid, has shown a high efficacy rate in treating drug-resistant TB.
• Ongoing Trials: Ongoing and future clinical trials, such as the PAN-TB collaboration, are aimed at optimizing treatment regimens and expanding access.
• Market Growth: The global TB drugs market is expected to grow significantly, driven by the need for effective treatments for drug-resistant TB.
• Regulatory Approvals: Pretomanid has received significant regulatory approvals, including FDA approval and WHO prequalification.

FAQs

What is pretomanid used for?

Pretomanid is used for the treatment of highly drug-resistant forms of tuberculosis, including extensively drug-resistant tuberculosis (XDR-TB) and treatment-intolerant/nonresponsive multidrug-resistant tuberculosis (TI/NR MDR-TB)[1].

How is pretomanid administered?

Pretomanid is administered orally as part of a three-drug combination regimen with bedaquiline and linezolid, taken once daily for six months[1].

What are the efficacy results of pretomanid clinical trials?

The clinical trials have shown that 95 out of 107 patients (89%) had no TB bacteria in the sputum six months after completing the treatment[1][4].

What are the ongoing clinical trials involving pretomanid?

The PAN-TB collaboration is conducting a phase 2b/c clinical trial to evaluate novel regimens that include pretomanid, and other trials like ZeNix and Nix-TB are optimizing the BPaL regimen[3][4].

What is the projected market size for TB drugs by 2025?

The global TB drugs market is expected to reach USD 1.38 billion by 2025, growing at a CAGR of 5.2% during the forecast period[5].

What are the regulatory approvals for pretomanid?

Pretomanid has been approved by the FDA, received EU marketing authorization, and has been listed by the WHO as a Prequalified Medicinal Product. It also received approval from the Drug Controller General of India (DCGI)[4].

Sources

1. FDA: Drug Trials Snapshots: PRETOMANID - FDA
2. Stop TB Partnership: Background and Introduction Day 1 - Stop TB Partnership
3. PR Newswire: PAN-TB Collaboration Announces the Start of a Phase 2 Clinical Trial
4. TB Alliance: The Pathway to Potential New TB Treatments
5. Grand View Research: TB Drugs Market Size Worth $1.38 Billion by 2025 | CAGR: 5.2%