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Pretomanid in Adults With Hepatic Impairment

Primary Purpose

Tuberculosis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PA-824
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring Hepatic, impairment, PA-824, Pharmacokinetics, Safety, Tuberculosis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Inclusion Criteria for Patients with Hepatic Impairment (Groups 1-3):

  1. Subject is able to give voluntary written informed consent before any study related procedure is performed.
  2. 18-70 years of age, inclusive.
  3. Acceptable laboratory values* obtained at screening (within 21 days prior to admission to the confinement/hospital unit) and either at or within 72 hours of admission to the confinement/hospital unit.

    *Chemistry, complete blood count, AST, ALT, total bilirubin, alkaline phosphatase, albumin, and urinalysis deemed not clinically significant by the investigator.

  4. Hepatic impairment classified as Child-Pugh class A (mild), B (moderate), or C (severe) criteria at screening for Groups 1, 2, or 3, respectively, and documented evidence of hepatic cirrhosis*.

    *by biopsy, nuclear scan, CT, MRI, ultrasound, or other clinically acceptable methods

  5. If female, not of childbearing potential* or agrees to avoid becoming pregnant by using acceptable contraception** during the duration of the study.

    *Non-childbearing potential is defined as being post-menopausal for at least 2 years, status after bilateral oophorectomy or status after hysterectomy.

    • Females of childbearing potential must agree to use two acceptable methods of contraceptives: bilateral tubal ligation; barrier method (condom) by the male partner (even if vasectomized); hormonal contraceptives; intrauterine contraceptive devices; diaphragm in combination with contraceptive jelly, cream, foam, or spermicide; and abstinence from sexual intercourse with men.
  6. If subject is male and capable of reproduction, agrees to avoid fathering a child for three months after dosing by using an acceptable method of birth control*.

    *In addition to the use of a barrier method (condom) even if vasectomized, acceptable methods of birth control are restricted to a monogamous relationship with a woman who agrees to use acceptable contraception as outlined in inclusion criterion #5, and abstinence from sexual intercourse with women.

  7. If the subject is female, a negative serum pregnancy test at screening and a negative urine pregnancy test at admission to the confinement/hospital unit.
  8. Willingness to comply with all protocol requirements.

Inclusion Criteria for Non-Hepatically Impaired Controls (Group 4):

  1. Subject is able to give voluntary written informed consent before any study related procedure is performed.
  2. 18-70 years of age, inclusive.
  3. Subject is a healthy volunteer as determined by no clinically significant findings from medical history, physical examination, vital signs, and 12-lead ECG as determined by the Site Investigator.
  4. Acceptable laboratory values* obtained at screening (within 21 days prior to admission to the confinement/hospital unit) and either at or within 72 hours of admission to the confinement/hospital unit.

    *Chemistry, complete blood count, AST, ALT, total bilirubin, alkaline phosphatase, albumin, and urinalysis within the reference range for the test laboratory, unless deemed not clinically significant by the investigator.

  5. If female, not of childbearing potential* or agrees to avoid becoming pregnant by using acceptable contraception** during the duration of the study.

    *Non-childbearing potential is defined as being post-menopausal for at least 2 years, status after bilateral oophorectomy or status after hysterectomy.

    **Females of childbearing potential must agree to use two acceptable methods of contraceptives: bilateral tubal ligation; barrier method (condom) by the male partner (even if vasectomized); hormonal contraceptives; intrauterine contraceptive devices; diaphragm in combination with contraceptive jelly, cream, foam, or spermicide; and abstinence from sexual intercourse with men.

  6. If subject is male and capable of reproduction, agrees to avoid fathering a child for three months after dosing by using an acceptable method of birth control*.

    *In addition to the use of a barrier method (condom) even if vasectomized, acceptable methods of birth control are restricted to a monogamous relationship with a woman who agrees to use acceptable contraception as outlined in inclusion criterion #5, and abstinence from sexual intercourse with women.

  7. If the subject is female, a negative serum pregnancy test at screening and a negative urine pregnancy test at admission to the confinement/hospital unit.
  8. Willingness to comply with all protocol requirements.

Exclusion Criteria:

Exclusion Criteria for Patients with Hepatic Impairment (Groups 1-3):

  1. Hypokalemia (< 3.5mEq/L), severe hypomagnesemia (< 1.1 mg/dL) or severe hypocalcemia (< 7.5 mg/dL).
  2. AST or ALT > 10 times the upper limit of normal.
  3. Creatinine clearance < 60 ml/min.
  4. Inability to swallow tablets.
  5. Presence of any condition or finding* which would jeopardize subject safety, impact study result validity, or diminish the subject's ability to undergo all study procedures and assessments**.

    *in the opinion of the site investigator

    **e.g., inability to draw PK samples

  6. History of fever or documented fever (oral temperature > / = 100.4 degrees F or > / = 38.0 degrees C) in the 48 hours prior to admission to the the confinement/hospital unit.
  7. Currently breastfeeding.
  8. History of chronic tobacco/nicotine use (> 10 cigarettes per day for 3 months minimum prior to admission).
  9. History of clinically significant allergy or severe side effects with nitroimidazoles (e.g., Metronidazole and related substances and azole antifungals or aromatase inhibitors).
  10. Receipt of an investigational drug, vaccine or biologic in a clinical trial within 30 days prior to screening.
  11. Use of any over the counter (OTC) medication* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results.

    *including vitamins and herbal supplements, cough and cold medications.

    **in the opinion of the site investigator

  12. Treatment with CYP450 enzyme altering drugs* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results.

    • except hormonal contraceptives

      • in the opinion of the site investigator NOTE: See list of CYP450 enzyme altering drugs under the concomitant medications section.
  13. A positive blood screen for HIV.
  14. A positive alcohol breath test (or other suitable test for alcohol) or a urine screen test for drugs of abuse* at screening and at admission to the confinement/hospital unit.

    *Amphetamines, barbiturates, cocaine metabolites, marijuana, opiates, phencyclidine (PCP).

    NOTE: Results of the urine screen test can be ignored if in the opinion of the PI the results can be explained by the concomitant medications history.

  15. Unwillingness to abstain from engaging in strenuous physical activity (e.g. running, bicycling, weightlifting, competitive sports) during the course of the study.
  16. Consumption of grapefruit juice in the 48 hours before admission to the confinement/hospital unit, or the inability to abstain from these until completion of Day 12.
  17. A QTcF interval > 450 msec (males) or > 450 msec (females) at screening (Visit 00A) or admission to the confinement/hospital unit (Visit 00B) or a history of prolonged QTc interval.
  18. A 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.

    *parents

    **due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women)

    ***such as known coronary artery disease, congestive heart failure, or terminal cancer

  19. Any clinically significant ECG abnormality, in the opinion of the site investigator, at screening and at admission to the confinement/hospital unit.
  20. Donation of > 500 mL blood within the 30 days prior to admission to the confinement/hospital unit.
  21. Plans to donate blood during the study or up to 14 days after dosing.
  22. Persons with a transjugular intrahepatic portosystemic shunt.

Exclusion Criteria for Non-Hepatically Impaired Controls (Group 4):

  1. Inability to swallow tablets.
  2. Presence of any condition or finding* which would jeopardize subject safety, impact study result validity, or diminish the subject's ability to undergo all study procedures and assessments**.

    *in the opinion of the site investigator

    **e.g., inability to collect PK samples

  3. History of fever or documented fever (oral temperature > / = 100.4 degrees F or > / = 38.0 degrees C) in the 48 hours prior to admission to the confinement/hospital unit.
  4. Currently breastfeeding.
  5. History of chronic tobacco/nicotine use (> 10 cigarettes per day for 3 months minimum prior to admission to the confinement/hospital unit).
  6. History of seizures (other than febrile seizures during childhood) or known or suspected CNS disorders that may predispose to seizures.
  7. History of clinically significant allergy or severe side effects with nitroimidazoles (e.g., Metronidazole and related substances and azole antifungals or aromatase inhibitors).
  8. Receipt of an investigational drug, vaccine or biologic in a clinical trial within 30 days prior to screening.
  9. Use of any over the counter (OTC) medication* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results.

    *including vitamins and herbal supplements, antacids, cough and cold medications.

    **in the opinion of the site investigator

  10. Use of prescription medication except hormonal contraceptives within 30 days prior to admission to the confinement/hospital unit, unless* the substance would not likely impact study result validity.

    *in the opinion of the site investigator

  11. Treatment with CYP450 enzyme altering drugs* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results.

    *except hormonal contraceptives

    **in the opinion of the site investigator NOTE: See list of CYP450 enzyme altering drugs under the concomitant medications section.

  12. A positive blood screen for HIV.
  13. A positive blood screen for hepatitis B surface antigen (HBsAg), or hepatitis C antibody.
  14. A positive alcohol breath test (or other suitable test for alcohol) or a urine screen test for drugs of abuse* at screening and at admission to the confinement/hospital unit.

    *Amphetamines, barbiturates, benzodiazepines, cocaine metabolites, marijuana, opiates, phencyclidine (PCP).

  15. A history of alcohol abuse or dependence within the past 1 month prior to admission to the confinement/hospital unit.
  16. Unwillingness to abstain from engaging in strenuous physical activity (e.g. running, bicycling, weightlifting, competitive sports) during the course of the study.
  17. Consumption of grapefruit juice in the 48 hours before admission to the confinement/hospital unit, or the inability to abstain from these until completion of Day 12.
  18. A QTcF interval > 450 msec (males) or > 450 msec (females) at screening (Visit 00A) or admission to the confinement/hospital unit (Visit 00B) or a history of prolonged QTc interval.
  19. A 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.

    *parents

    **due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women)

    ***such as known coronary artery disease, congestive heart failure, or terminal cancer

  20. Any clinically significant ECG abnormality, in the opinion of the site investigator, at screening and at admission to the confinement/hospital unit.
  21. Donation of > 500 mL of blood within the 30 days prior to admission to the confinement/hospital unit.
  22. Plans to donate blood during the study or up to 14 days after dosing.
  23. Persons with a transjugular intrahepatic portosystemic shunt.

Sites / Locations

  • Saint Louis University Center for Vaccine DevelopmentRecruiting
  • Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research UnitRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Child-Pugh A (Mild hepatic impairment)

Child-Pugh B (Moderate hepatic impairment)

Child-Pugh C (Severe hepatic impairment)

Non-hepatically impaired controls

Arm Description

6 Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1

6 Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1

6 Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1

18 matched Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1

Outcomes

Primary Outcome Measures

AUC(0-infinity): Area under the concentration time-curve extrapolated to infinity at specified pre-dose and post-dose time points
AUC(0-last): Area under the concentration time-curve to the last concentration above the lower limit of quantitation at specified pre-dose and post-dose time points
CL/F: Apparent oral clearance calculated from Dose/AUC(0-infinifty) at specified pre-dose and post-dose time points
Cmax: Maximum Pretomanid concentration at specified pre-dose and post-dose time points
t(1/2): Apparent terminal elimination half-life at specified pre-dose and post-dose time points
Tmax: Time of maximum Pretomanid concentration at specified pre-dose and post-dose time points
Vd/F: Apparent Volume of Distribution at specified pre-dose and post-dose time points

Secondary Outcome Measures

Incidence of related adverse events
Incidence of serious adverse events
Severity of related adverse events
Severity of serious adverse events
Summary of ECG data
Summary of physical examination findings (height at baseline, and weight at serial time points)
Summary of safety laboratory parameters
Summary of vital signs at serial time points

Full Information

First Posted
April 16, 2015
Last Updated
September 7, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT02422524
Brief Title
Pretomanid in Adults With Hepatic Impairment
Official Title
A Phase I, Single Dose, Open-Label Study Comparing the Pharmacokinetics and Safety of Pretomanid in Subjects With Mild, Moderate, and Severe Hepatic Impairment to Matched, Non-Hepatically Impaired Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 11, 2017 (Actual)
Primary Completion Date
August 31, 2023 (Anticipated)
Study Completion Date
August 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
This is a Phase 1, single dose (200 mg), open-label 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.
Detailed Description
This is a Phase 1, single dose (200 mg), open-label study comparing the pharmacokinetics and safety of Pretomanid in subjects with mild, moderate, and severe hepatic impairment to matched, non-hepatically impaired subjects. This study will enroll approximately 6 subjects with mild hepatic impairment (Child-Pugh A), approximately 6 subjects with moderate hepatic impairment (Child-Pugh B), approximately 6 subjects with severe hepatic impairment (Child-Pugh C), and approximately 18 matched non-hepatically impaired subjects. Non-hepatically impaired subjects in the control group will be matched to subjects with hepatic impairment based on age (+/- 10 years) and body weight (+/- 20 percent) as measured at screening (Visit 00A). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Hepatic, impairment, PA-824, Pharmacokinetics, Safety, Tuberculosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Child-Pugh A (Mild hepatic impairment)
Arm Type
Experimental
Arm Description
6 Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1
Arm Title
Child-Pugh B (Moderate hepatic impairment)
Arm Type
Experimental
Arm Description
6 Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1
Arm Title
Child-Pugh C (Severe hepatic impairment)
Arm Type
Experimental
Arm Description
6 Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1
Arm Title
Non-hepatically impaired controls
Arm Type
Experimental
Arm Description
18 matched Subjects will receive a single oral dose of 200mg Pretomanid tablets on day 1
Intervention Type
Drug
Intervention Name(s)
PA-824
Intervention Description
Pretomanid (PA-824) is a nitroimidazooxazine. All subjects will receive a single oral dose of 200 mg Pretomanid on day 1.
Primary Outcome Measure Information:
Title
AUC(0-infinity): Area under the concentration time-curve extrapolated to infinity at specified pre-dose and post-dose time points
Time Frame
Day 1 to Day 5
Title
AUC(0-last): Area under the concentration time-curve to the last concentration above the lower limit of quantitation at specified pre-dose and post-dose time points
Time Frame
Day 1 to Day 5
Title
CL/F: Apparent oral clearance calculated from Dose/AUC(0-infinifty) at specified pre-dose and post-dose time points
Time Frame
Day 1 to Day 5
Title
Cmax: Maximum Pretomanid concentration at specified pre-dose and post-dose time points
Time Frame
Day 1 to Day 5
Title
t(1/2): Apparent terminal elimination half-life at specified pre-dose and post-dose time points
Time Frame
Day 1 to Day 5
Title
Tmax: Time of maximum Pretomanid concentration at specified pre-dose and post-dose time points
Time Frame
Day 1 to Day 5
Title
Vd/F: Apparent Volume of Distribution at specified pre-dose and post-dose time points
Time Frame
Day 1 to Day 5
Secondary Outcome Measure Information:
Title
Incidence of related adverse events
Time Frame
Day 1 to Day 12
Title
Incidence of serious adverse events
Time Frame
Day 1 to Day 12
Title
Severity of related adverse events
Time Frame
Day 1 to Day 12
Title
Severity of serious adverse events
Time Frame
Day 1 to Day 12
Title
Summary of ECG data
Time Frame
Day -1 and Day 12
Title
Summary of physical examination findings (height at baseline, and weight at serial time points)
Time Frame
Day -1 to Day 12
Title
Summary of safety laboratory parameters
Time Frame
Day -1, 2, 5, and 12
Title
Summary of vital signs at serial time points
Time Frame
Day -1 to Day 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Inclusion Criteria for Patients with Hepatic Impairment (Groups 1-3): Subject is able to give voluntary written informed consent before any study related procedure is performed. 18-70 years of age, inclusive. Acceptable laboratory values* obtained at screening (within 21 days prior to admission to the confinement/hospital unit) and either at or within 72 hours of admission to the confinement/hospital unit. *Chemistry, complete blood count, AST, ALT, total bilirubin, alkaline phosphatase, albumin, and urinalysis deemed not clinically significant by the investigator. Hepatic impairment classified as Child-Pugh class A (mild), B (moderate), or C (severe) criteria at screening for Groups 1, 2, or 3, respectively, and documented evidence of hepatic cirrhosis*. *by biopsy, nuclear scan, CT, MRI, ultrasound, or other clinically acceptable methods If female, not of childbearing potential* or agrees to avoid becoming pregnant by using acceptable contraception** during the duration of the study. *Non-childbearing potential is defined as being post-menopausal for at least 2 years, status after bilateral oophorectomy or status after hysterectomy. Females of childbearing potential must agree to use two acceptable methods of contraceptives: bilateral tubal ligation; barrier method (condom) by the male partner (even if vasectomized); hormonal contraceptives; intrauterine contraceptive devices; diaphragm in combination with contraceptive jelly, cream, foam, or spermicide; and abstinence from sexual intercourse with men. If subject is male and capable of reproduction, agrees to avoid fathering a child for three months after dosing by using an acceptable method of birth control*. *In addition to the use of a barrier method (condom) even if vasectomized, acceptable methods of birth control are restricted to a monogamous relationship with a woman who agrees to use acceptable contraception as outlined in inclusion criterion #5, and abstinence from sexual intercourse with women. If the subject is female, a negative serum pregnancy test at screening and a negative urine pregnancy test at admission to the confinement/hospital unit. Willingness to comply with all protocol requirements. Inclusion Criteria for Non-Hepatically Impaired Controls (Group 4): Subject is able to give voluntary written informed consent before any study related procedure is performed. 18-70 years of age, inclusive. Subject is a healthy volunteer as determined by no clinically significant findings from medical history, physical examination, vital signs, and 12-lead ECG as determined by the Site Investigator. Acceptable laboratory values* obtained at screening (within 21 days prior to admission to the confinement/hospital unit) and either at or within 72 hours of admission to the confinement/hospital unit. *Chemistry, complete blood count, AST, ALT, total bilirubin, alkaline phosphatase, albumin, and urinalysis within the reference range for the test laboratory, unless deemed not clinically significant by the investigator. If female, not of childbearing potential* or agrees to avoid becoming pregnant by using acceptable contraception** during the duration of the study. *Non-childbearing potential is defined as being post-menopausal for at least 2 years, status after bilateral oophorectomy or status after hysterectomy. **Females of childbearing potential must agree to use two acceptable methods of contraceptives: bilateral tubal ligation; barrier method (condom) by the male partner (even if vasectomized); hormonal contraceptives; intrauterine contraceptive devices; diaphragm in combination with contraceptive jelly, cream, foam, or spermicide; and abstinence from sexual intercourse with men. If subject is male and capable of reproduction, agrees to avoid fathering a child for three months after dosing by using an acceptable method of birth control*. *In addition to the use of a barrier method (condom) even if vasectomized, acceptable methods of birth control are restricted to a monogamous relationship with a woman who agrees to use acceptable contraception as outlined in inclusion criterion #5, and abstinence from sexual intercourse with women. If the subject is female, a negative serum pregnancy test at screening and a negative urine pregnancy test at admission to the confinement/hospital unit. Willingness to comply with all protocol requirements. Exclusion Criteria: Exclusion Criteria for Patients with Hepatic Impairment (Groups 1-3): Hypokalemia (< 3.5mEq/L), severe hypomagnesemia (< 1.1 mg/dL) or severe hypocalcemia (< 7.5 mg/dL). AST or ALT > 10 times the upper limit of normal. Creatinine clearance < 60 ml/min. Inability to swallow tablets. Presence of any condition or finding* which would jeopardize subject safety, impact study result validity, or diminish the subject's ability to undergo all study procedures and assessments**. *in the opinion of the site investigator **e.g., inability to draw PK samples History of fever or documented fever (oral temperature > / = 100.4 degrees F or > / = 38.0 degrees C) in the 48 hours prior to admission to the the confinement/hospital unit. Currently breastfeeding. History of chronic tobacco/nicotine use (> 10 cigarettes per day for 3 months minimum prior to admission). History of clinically significant allergy or severe side effects with nitroimidazoles (e.g., Metronidazole and related substances and azole antifungals or aromatase inhibitors). Receipt of an investigational drug, vaccine or biologic in a clinical trial within 30 days prior to screening. Use of any over the counter (OTC) medication* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results. *including vitamins and herbal supplements, cough and cold medications. **in the opinion of the site investigator Treatment with CYP450 enzyme altering drugs* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results. except hormonal contraceptives in the opinion of the site investigator NOTE: See list of CYP450 enzyme altering drugs under the concomitant medications section. A positive blood screen for HIV. A positive alcohol breath test (or other suitable test for alcohol) or a urine screen test for drugs of abuse* at screening and at admission to the confinement/hospital unit. *Amphetamines, barbiturates, cocaine metabolites, marijuana, opiates, phencyclidine (PCP). NOTE: Results of the urine screen test can be ignored if in the opinion of the PI the results can be explained by the concomitant medications history. Unwillingness to abstain from engaging in strenuous physical activity (e.g. running, bicycling, weightlifting, competitive sports) during the course of the study. Consumption of grapefruit juice in the 48 hours before admission to the confinement/hospital unit, or the inability to abstain from these until completion of Day 12. A QTcF interval > 450 msec (males) or > 450 msec (females) at screening (Visit 00A) or admission to the confinement/hospital unit (Visit 00B) or a history of prolonged QTc interval. A 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. *parents **due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women) ***such as known coronary artery disease, congestive heart failure, or terminal cancer Any clinically significant ECG abnormality, in the opinion of the site investigator, at screening and at admission to the confinement/hospital unit. Donation of > 500 mL blood within the 30 days prior to admission to the confinement/hospital unit. Plans to donate blood during the study or up to 14 days after dosing. Persons with a transjugular intrahepatic portosystemic shunt. Exclusion Criteria for Non-Hepatically Impaired Controls (Group 4): Inability to swallow tablets. Presence of any condition or finding* which would jeopardize subject safety, impact study result validity, or diminish the subject's ability to undergo all study procedures and assessments**. *in the opinion of the site investigator **e.g., inability to collect PK samples History of fever or documented fever (oral temperature > / = 100.4 degrees F or > / = 38.0 degrees C) in the 48 hours prior to admission to the confinement/hospital unit. Currently breastfeeding. History of chronic tobacco/nicotine use (> 10 cigarettes per day for 3 months minimum prior to admission to the confinement/hospital unit). History of seizures (other than febrile seizures during childhood) or known or suspected CNS disorders that may predispose to seizures. History of clinically significant allergy or severe side effects with nitroimidazoles (e.g., Metronidazole and related substances and azole antifungals or aromatase inhibitors). Receipt of an investigational drug, vaccine or biologic in a clinical trial within 30 days prior to screening. Use of any over the counter (OTC) medication* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results. *including vitamins and herbal supplements, antacids, cough and cold medications. **in the opinion of the site investigator Use of prescription medication except hormonal contraceptives within 30 days prior to admission to the confinement/hospital unit, unless* the substance would not likely impact study result validity. *in the opinion of the site investigator Treatment with CYP450 enzyme altering drugs* within 7 days prior to admission to the confinement/hospital unit, unless** the substance would not likely impact the validity of the study results. *except hormonal contraceptives **in the opinion of the site investigator NOTE: See list of CYP450 enzyme altering drugs under the concomitant medications section. A positive blood screen for HIV. A positive blood screen for hepatitis B surface antigen (HBsAg), or hepatitis C antibody. A positive alcohol breath test (or other suitable test for alcohol) or a urine screen test for drugs of abuse* at screening and at admission to the confinement/hospital unit. *Amphetamines, barbiturates, benzodiazepines, cocaine metabolites, marijuana, opiates, phencyclidine (PCP). A history of alcohol abuse or dependence within the past 1 month prior to admission to the confinement/hospital unit. Unwillingness to abstain from engaging in strenuous physical activity (e.g. running, bicycling, weightlifting, competitive sports) during the course of the study. Consumption of grapefruit juice in the 48 hours before admission to the confinement/hospital unit, or the inability to abstain from these until completion of Day 12. A QTcF interval > 450 msec (males) or > 450 msec (females) at screening (Visit 00A) or admission to the confinement/hospital unit (Visit 00B) or a history of prolonged QTc interval. A 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. *parents **due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women) ***such as known coronary artery disease, congestive heart failure, or terminal cancer Any clinically significant ECG abnormality, in the opinion of the site investigator, at screening and at admission to the confinement/hospital unit. Donation of > 500 mL of blood within the 30 days prior to admission to the confinement/hospital unit. Plans to donate blood during the study or up to 14 days after dosing. Persons with a transjugular intrahepatic portosystemic shunt.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julius Wilder
Phone
19196848111
Email
julius.wilder@dm.duke.edu
Facility Information:
Facility Name
Saint Louis University Center for Vaccine Development
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104-1015
Country
United States
Individual Site Status
Recruiting
Facility Name
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710-4000
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

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Pretomanid in Adults With Hepatic Impairment

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