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Pretomanid for Kidney Failure

No longer recruiting at 4 trial locations

Overseen ByWilliam B Smith

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: Active TB, Peptic ulcer, Cardiac abnormality, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Approved in 3 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study the effects of pretomanid (PA-824) on individuals with varying levels of kidney function. Researchers seek to understand how the drug behaves in the body and assess its safety for those with kidney issues, including severe kidney failure, compared to individuals with normal kidney function. Participants will take a single dose of the drug, and researchers will monitor its presence in the blood and urine. The trial suits individuals with different kidney problems who are not on dialysis and do not smoke heavily. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take strong or moderate CYP3A4 inducers or inhibitors within 14 days before admission and during the study, and you should avoid St. John's Wort and grapefruit products before and during the study.

Is there any evidence suggesting that pretomanid is likely to be safe for humans?

Research shows that the safety of pretomanid for people with kidney problems remains unknown. No studies have yet assessed its safety or effectiveness for those with kidney issues. As a result, there is no clear information on how the drug affects individuals with kidney failure or other kidney-related problems.

This is an early phase study, aimed at understanding pretomanid’s safety and its mechanism in the body. Early phase trials typically mark the first step in testing a new treatment in humans. They help researchers determine if the treatment is safe and identify any side effects.

Pretomanid is approved for other uses but not for kidney failure. It has been tested and found safe for other conditions, but its safety for kidney problems is still under investigation. Participants in the trial will be closely monitored to observe how their bodies respond to the treatment.¹ ² ³ ⁴ ⁵

Why do researchers think this study treatment might be promising for kidney failure?

Researchers are excited about pretomanid for kidney failure because it offers a potentially innovative approach compared to standard treatments like dialysis and kidney transplantation. Unlike these traditional methods, pretomanid is an oral medication, which could provide a less invasive and more convenient option for patients. Additionally, pretomanid might offer a new mechanism of action by targeting specific pathways involved in kidney function, potentially improving outcomes for those with renal impairment. This novel approach could lead to more effective management of kidney failure, providing hope for improved patient quality of life.

What evidence suggests that pretomanid might be an effective treatment for kidney failure?

Research shows that the effectiveness of pretomanid for people with kidney failure remains uncertain. Pretomanid treats certain types of tuberculosis, but its effects on individuals with varying kidney functions have not been extensively studied. This trial will explore its pharmacokinetics and safety across various treatment arms, including participants with mild, moderate, and severe renal impairment, as well as healthy participants for comparison. Clear information on its effectiveness or safety for those with kidney issues is lacking. As this is a new research area, the trials aim to understand how the drug moves and works in the bodies of people with kidney problems.¹ ² ⁴ ⁶ ⁷

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with varying degrees of kidney function, from normal to severe impairment, but not on dialysis. Participants must be non-smokers, have a healthy weight range (BMI 18-35), and a normal heart rhythm. Women should not be pregnant and must use birth control; men agree to prevent pregnancy during the study.

Inclusion Criteria

Subject Inclusion Criteria for Patients with Renal Impairment (Groups 2-4): Have the ability to understand the requirements of the study and have provided written informed consent before any study related procedure is performed. Agree to abide by the study restrictions. Are between the ages of 18 and 70, inclusive, at the time of enrollment. Must have mild, moderate, severe or end stage renal disease but are not on dialysis. Are free from tobacco/nicotine usage (30-day minimum from screening visit). Have QTc interval on electrocardiogram (ECG) < 500 msec. Have a body mass index of 18 to 35 kg/m^2. Women of childbearing potential must use an acceptable contraception method for the duration of the study. If subject is male and capable of reproduction, agrees to avoid fathering a child for the duration of the study by using an acceptable method of birth control. Women of childbearing potential must have a negative urine pregnancy test within 24 hours prior to receipt of study product

Subject Inclusion Criteria for Healthy Subjects (Groups 1A-1C): Have the ability to understand the requirements of the study and have provided written informed consent before any study related procedure is performed. Agree to abide by the study restrictions. Are healthy male or non-pregnant female, between the ages of 18 and 70, inclusive, with normal GFR > / = 90 at screening. Are free from tobacco/nicotine usage (30-day minimum from screening visit). Have a normal QTc interval < 500 msecs on electrocardiogram (ECG). Have a body mass index of 18 to 35 kg/m^2. Women of childbearing potential must use an acceptable contraception method for the duration of the study. If subject is male and capable of reproduction, agrees to avoid fathering a child for the duration of the study by using an acceptable method of birth control. Women of childbearing potential must have a negative urine pregnancy test within 24 hours prior to receipt of study product

Exclusion Criteria

The exclusion criteria for healthy subjects are: - History of active tuberculosis - History of peptic ulcer disease - Allergy to pretomanid or any of its components - Uncontrolled heart problems - Abnormal heart rhythm - Family history of Long-QT Syndrome or sudden death - Difficulty swallowing tablets - Recent fever - Resting pulse rate too low or too high - High or low blood pressure - Abnormal heart rhythm history - Low potassium or magnesium levels - Positive urine drug screen or blood alcohol screen - Significant history of drug and/or food allergies - Pregnancy, breastfeeding, or planning to conceive during the study - Inability to use nitromidazoles or previously treated with pretomanid or delamanid - Use of certain medications within 7 days prior to admission - Use of St. John's Wort or grapefruit products within specific timeframes - Recent blood donation - Recent participation in another clinical trial - Low hemoglobin levels - Positive screening test for HCV, HBV, or HIV - Renal transplant - Any condition that could affect safety or study results - Semen donation during the study - Abnormal liver function tests

Criterion: You cannot participate if you have a history of active tuberculosis, peptic ulcer disease, allergy to the study drug, uncontrolled heart problems, abnormal heart readings, swallowing difficulties, recent fever, abnormal pulse rate, low potassium or magnesium levels, recent alcohol or drug use, strong drug interactions, use of certain herbal supplements or grapefruit products, recent blood donation, recent participation in another clinical trial, low hemoglobin levels, positive test for hepatitis or HIV, kidney transplant, or any condition that could affect your safety or the study results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A - Reduced PK Study

Participants receive a single oral dose of 200 mg pretomanid to evaluate pharmacokinetics and safety in severe renal impairment and matched healthy controls

Up to 96 hours

1 visit (in-person)

Part B - Full PK Study

Participants with mild and moderate renal impairment receive a single oral dose of 200 mg pretomanid after review of Part A results

Up to 96 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

PA-824

Trial Overview The study tests how a single dose of Pretomanid (PA-824) behaves in the body (its pharmacokinetics) in people with different levels of kidney health compared to those with normal kidneys. It involves taking one oral dose and monitoring its presence in blood and urine over three months.

How Is the Trial Designed?

6Treatment groups

Experimental Treatment

Active Control

Group I: Part B Group 4Experimental Treatment1 Intervention

6 participants with moderate renal impairment: Stage 3, Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR = 30-59 mL/min) matched to Group 1C will receive a single oral dose of 200 mg pretomanid after the PK and safety of subjects enrolled in Part A have been reviewed

Group II: Part B Group 3Experimental Treatment1 Intervention

6 participants with mild renal impairment: Stage 2, Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR 60-89 mL/min) matched to Group 1B will receive a single oral dose of 200 mg pretomanid after the PK and safety of subjects enrolled in Part A have been reviewed

Group III: Part A Group 2Experimental Treatment1 Intervention

6 participants with severe renal impairment: Stage 4, Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR 15-29 mL/min), and End Stage Renal Disease (ESRD) not on dialysis: Stage 5, Modification of Diet in Renal Disease (MDRD) with estimated Glomerular Filtration Rate (eGFR \< 15 mL/min) matched to Group 1A will receive a single oral dose of 200 mg pretomanid

Group IV: Part A Group 1AActive Control1 Intervention

6 healthy participants with normal renal function: Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR \> / = 90 mL/min) matched to Group 2 by race, gender, age (+/- 10 years, but between 18 to 85 years of age) and body mass index (BMI) (18 to 40 kg/m\^2) will receive a single oral dose of 200 mg pretomanid

Group V: Part B Group 1BActive Control1 Intervention

6 healthy participants with Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR of \> / = 90 mL/min) matched to Group 3 by race, gender, age (+/- 10 years, but between 18 to 85 years of age) and body mass index (BMI) (18 to 40 kg/m\^2) will receive a single oral dose of 200 mg pretomanid after the PK and safety of subjects enrolled in Part A have been reviewed

Group VI: Part B Group 1CActive Control1 Intervention

6 healthy participants: with Modification of Diet in Renal Disease (MDRD) estimated Glomerular Filtration Rate (eGFR \> / = 90 mL/min) matched to Group 4 by race, gender, age (+/- 10 years, but between 18 to 85 years of age) and body mass index (BMI) (18 to 40 kg/m\^2) will receive a single oral dose of 200 mg pretomanid after the PK and safety of subjects enrolled in Part A have been reviewed

PA-824 is already approved in United States, European Union, India for the following indications:

Approved in United States as Pretomanid for:

Multidrug-resistant tuberculosis
Extensively drug-resistant tuberculosis

Approved in European Union as Pretomanid for:

Multidrug-resistant tuberculosis
Extensively drug-resistant tuberculosis

Approved in India as Pretomanid for:

Multidrug-resistant tuberculosis
Extensively drug-resistant tuberculosis

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Doripenem, at a concentration of 5 mg/mL, demonstrated stability for up to 12 hours in 0.9% sodium chloride at room temperature, making it suitable for extended infusions.

The study confirmed that doripenem retains its potency and safety profile when prepared and stored properly, allowing for effective treatment of complicated infections within a practical time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of doripenem in vitro in representative infusion solutions and infusion bags.Psathas, PA., Kuzmission, A., Ikeda, K., et al.[2018]

Direct oral anticoagulants (DOACs) can be beneficial for patients with mild to moderate chronic kidney disease (CKD), especially those who cannot tolerate vitamin K antagonists, but their use in patients with severe renal impairment remains challenging due to limited data.

DOACs are not approved for patients with end-stage renal disease (ESRD) or those on dialysis, and careful monitoring of renal function is crucial for patients with CKD to avoid complications, particularly in high-risk groups like the elderly and diabetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DOAC use in patients with chronic kidney disease.Kcükköylü, S., Rump, LC.[2019]

Direct oral anticoagulants (DOACs) can be safely used in patients with chronic kidney disease (CKD) who have an estimated glomerular filtration rate (eGFR) above 60 mL/min, offering greater efficacy and safety compared to vitamin K antagonists (VKAs).

In patients with CKD stage 3, DOACs are as effective as VKAs but have a lower risk of bleeding; however, their use should be avoided in patients with an eGFR below 30 mL/min due to increased bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations.Lutz, J., Jurk, K., Schinzel, H.[2022]

Citations

1.accessdata.fda.govaccessdata.fda.gov/drugsatfda_docs/label/2019/212862s000lbl.pdf

pretomanid tablets - accessdata.fda.govRenal Impairment. 8.7. The effect of renal impairment on the safety, effectiveness, and pharmacokinetics of pretomanid is not known. OVERDOSAGE. 10. There is no ...

2.ema.europa.euema.europa.eu/en/documents/product-information/dovprela-epar-product-information_en.pdf

Dovprela, INN-pretomanid - European Medicines AgencyRenal impairment The safety and efficacy of pretomanid in populations with renal impairment have not been established. No data are available. Use in patients ...

3.accessdata.fda.govaccessdata.fda.gov/drugsatfda_docs/label/2024/212862s008lbl.pdf

pretomanid tablets - accessdata.fda.gov8.7 Renal Impairment. The effect of renal impairment on the safety, effectiveness, and pharmacokinetics of pretomanid is not known. 10. OVERDOSAGE. There is no ...

4.extranet.who.intextranet.who.int/prequal/sites/default/files/whopar_files/tb397part4v1.pdf

WHO-PQ RECOMMENDED SUMMARY OF PRODUCT ...The safety and efficacy of pretomanid in patients with renal impairment have not been established.

5.clinicaltrials.govclinicaltrials.gov/study/NCT07126639

NCT07126639 | A Study on the Short-course Treatment ...Under the guidance of rapid molecular drug susceptibility test results, the experimental group will be treated with bedaquiline, pretomanid, ...

6.withpower.comwithpower.com/trial/phase-1-renal-insufficiency-7-2019-ceeb9?condition=tuberculosis&overallStatus=Recruiting&hasNoPlacebo=false

Pretomanid for Kidney Failure · Info for ParticipantsWhat safety data exists for Pretomanid in treating kidney failure? The provided research does not contain safety data for Pretomanid (also known as PA-824 ...

7.efda.gov.etefda.gov.et/wp-content/uploads/2022/10/Summary-of-product-characteristics-for-DOVPRELA-Pretomanid-Tablets-200-mg.pdf

SUMMARY OF PRODUCT CHARACTERISTICSRenal Impairment. The effect of renal impairment on the safety, effectiveness, and pharmacokinetics of pretomanid is not known. Assessments ...

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Pretomanid for Kidney Failure

What You Need to Know Before You Apply

Are You a Good Fit for This Trial?

Timeline for a Trial Participant

What Are the Treatments Tested in This Trial?

Find a Clinic Near You

Who Is Running the Clinical Trial?

Published Research Related to This Trial

Citations

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