Health Condition 1: K729- Hepatic failure, unspecified
Conditions
Interventions
Intervention1: Nil: Nil
Intervention2: Pretomanid tablet 200 mg in patient with moderate hepatic impairment: Pretomanid 200 mg tablets Manufactured by Mylan Laboratories Limited, a viatris Company, In
Frequency: 1
Total duration of intervention: 13 days
Intervention6: Pretomanid tablet 200 mg in patient with severe hepatic impairment: Pretomanid 200 mg tablets Manufactured by Mylan Laboratories Limited, a viatr
Total duration of intervention: 13 days
Control Intervention1: Pretomanid 200 mg tablet: Pretomanid 200 mg tablets Manufactured by Mylan Laboratories Limited, a viatris Company, India
Control Interven
Total duration of intervention: 13 days
Sponsors
Mylan Laboratories Limited
Mylan Laboratories Limited
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Subjects with Moderate or Severe Hepatic Impairment Group 1 or 2 1 Males andor nonpregnant nonlactating females aged 18 to 70 years old inclusive 2 Each subject is required to weigh at least 50 kg and have a Body Mass Index BMI value less than or equal to 40 kg per m2 but greater than or equal to 18 kg per m2 3 Hepatically impaired subjects will be classified using Child Pugh System Subjects must have child Pugh B with the score of 7 to 9 moderate hepatic impairment or Child Pugh C with the score of 10 to 15 severe hepatic impairment with known medical history of liver disease with or without a known history of alcohol abuse and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique including laparoscopy computed tomography scan magnetic resonance imaging or ultrasonography associated with unambiguous medical history 4 Acceptable laboratory values obtained at screening within 21 days prior to admission to the clinical facility or study center and either at or within 72 hours of admission to the clinical facility or study center 5 A normal or non clinically significant physical examination skin head eyes ears nose and throat thyroid neurological chest and lungs cardiovascular abdomen liver and spleen lymph nodes musculoskeletal and extremities including vital signs sitting blood pressure mm Hg sitting heart rate beats per min and oral body temperature and 12lead ECG as determined by the clinical facility or study center Investigator 6 Adequate venous access in both arms for the collection of a number of blood samples during the study Inclusion Criteria for Non Hepatically Impaired Controls Group 3 1 Healthy Males and or nonpregnant nonlactating females aged 18 to 70 years old inclusive 2 Each subject is required to weigh at least 50 kg and have a Body Mass Index value less than or equal to 40 kg per m2 but greater than or equal to 18 kg per m2 Age 18 to 70 years old inclusive 3 The subjects will be matched to hepatic impaired subjects by age at screening The subject must meet age requirements at the time of signing the initial informed consent and the initial study medication administration 4 Subject is healthy as determined by no clinically significant findings from medical history physical examination skin head eyes ears nose and throat thyroid neurological chest and lungs cardiovascular abdomen liver and spleen lymph nodes musculoskeletal and extremities including vital signs sitting blood pressure mm Hg sitting heart rate beats min and oral body temperature and 12 lead ECG as determined by the clinical facility or study center Investigator 5 Acceptable laboratory values obtained at screening within 21 days prior to admission to the clinical facility or study center and either at or within 72 hours of admission to the clinical facility or study center 6 Adequate venous access in both arms for the collection of a number of blood samples during the study
Exclusion criteria
Exclusion criteria: Subject must not be enrolled in the study if they meet any of the following criteria Exclusion Criteria for Subjects with Moderate or Severe Hepatic Impairment Group 1 or 2 1 Institutionalized subjects 2 Subject with hypokalemia lesser than 3.5mEq per L severe hypomagnesemia lesser than 1.1 mg per dL or severe hypocalcemia lesser than 7.5 mg per dL 3 Aspartate aminotransferase AST or alanine transaminase ALT greater than 10 times the upper limit of normal 4 Creatinine clearance lesser than 60 ml per min per 1.73m2 5 Inability to swallow tablets 6 Any condition possibly affecting study drug absorption eg prior bariatric surgery gastrectomy ileal resection NOTE Participants who have undergone cholecystectomy and or appendectomy are eligible for this study as long as the surgery occurred more than 6 months prior to screening 7 Fluctuating or rapidly deteriorating hepatic function as indicated by widely varying or worsening of clinical and or laboratory signs of hepatic impairment 3 months prior to screening or within the screening period or the presence of any condition or finding which would jeopardize subject safety impact study result validity or diminish the subject ability to undergo all study procedures and assessment 8 History of fever or documented fever in the 48 hours prior to admission to the clinical facility or study center 9 History of clinically significant allergy or severe side effects with nitroimidazoles eg metronidazole and related substances and azole antifungals or aromatase inhibitors 10 Receipt of of a study drug vaccine or biologic in a clinical trial within 30 days prior to screening History of seizures other than febrile seizures during childhood or known or suspected CNS disorders that may predispose to seizures 11 Use of any over the counter OTCmedication within 7 days prior to admission to the clinical facility or study center unless the substance would not likely impact the validity of the study results 12 Treatment with CYP3A4 enzyme altering drugs within 7 days prior to admission to the clinical facility or study center unless the substance would not likely impact the validity of the study results 13 QTcF interval greater than 440 msec males or greater than 450 msec females at screening or admission to the clinical facility or study center or a history of prolonged QTc interval 14 History of seizures other than febrile seizures during childhood or known or suspected CNS disorders that may predispose to seizures 15 Family history of Long QT Syndrome premature cardiac death or sudden death without a preceding diagnosis of a condition that could be causative of sudden death 16 Any other clinically significant ECG abnormality in the opinion of the site investigator at screening and admission to the clinical facility or study center 17 Donated blood greater than 500 mL or significant blood loss within the 30 days prior to admission to the clinical facility or study center 18 Planning to donate blood during the study or up to 14 days after dosing 19 Persons with a transjugular intrahepatic portosystemic shunt 20 History of liver transplantation or subjects in the severe hepatic impairment group that are expecting a liver transplant during the study participation period 21 Medical history suggestive of hepatocellular carcinoma HCC with an alpha-fetoprot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the pharmacokinetics (PK) of pretomanid single dose in subjects with moderate and severe hepatic impairment (Child Pugh B and C, respectively) relative to matched control subjects with normal hepatic functionTimepoint: Blood samples (1 x 6 mL) will be collected in blood collection tubes containing K2EDTA before dosing (pre dose) and at the following times thereafter 1, 2, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of pretomanid in subjects with moderate and severe hepatic impairment relative to matched control subjects with normal hepatic function.Timepoint: Vital Signs and Safety will be obtained at screening, and on Day -1 to Day 12. | — |
Countries
India
Contacts
Public ContactDr Vasudev Shenoy
Ecron Acunova Limited
Outcome results
None listed