Trial Outcomes & Findings for Pretomanid in Adults With Hepatic Impairment (NCT NCT02422524)
NCT ID: NCT02422524
Last Updated: 2025-06-10
Results Overview
AUC(0-infinity) was calculated by noncompartmental analysis using the linear up log down method with the area extrapolated to infinity as Clast/Lambda\_z where Clast was the last observed concentration and Lambda\_z is the elimination rate constant.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
14 participants
Primary outcome timeframe
Day 1 to Day 5
Results posted on
2025-06-10
Participant Flow
Participants were hepatically impaired or non-hepatically impaired males and females, 18 to 70 years of age, inclusive, and met all eligibility criteria. Enrollment occurred between 29MAR2018 and 22AUG2023.
Participant milestones
| Measure |
Mild Hepatic Impairment
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
PA-824: Pretomanid (PA-824) is a nitroimidazooxazine.
|
Moderate Hepatic Impairment
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
PA-824: Pretomanid (PA-824) is a nitroimidazooxazine.
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
PA-824: Pretomanid (PA-824) is a nitroimidazooxazine.
|
Non-hepatically Impaired Controls
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
PA-824: Pretomanid (PA-824) is a nitroimidazooxazine.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
2
|
0
|
6
|
|
Overall Study
COMPLETED
|
6
|
2
|
0
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pretomanid in Adults With Hepatic Impairment
Baseline characteristics by cohort
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
62.8 years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
60.5 years
STANDARD_DEVIATION 3.5 • n=7 Participants
|
—
|
59 years
STANDARD_DEVIATION 7.1 • n=4 Participants
|
60.9 years
STANDARD_DEVIATION 5.5 • n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
—
|
6 participants
n=4 Participants
|
14 participants
n=21 Participants
|
|
BMI
|
31.3 kg/m^2
STANDARD_DEVIATION 8.0 • n=5 Participants
|
36.5 kg/m^2
STANDARD_DEVIATION 5.0 • n=7 Participants
|
—
|
27.9 kg/m^2
STANDARD_DEVIATION 4.4 • n=4 Participants
|
31.4 kg/m^2
STANDARD_DEVIATION 6.3 • n=21 Participants
|
|
Height
|
172.6 cm
STANDARD_DEVIATION 8.2 • n=5 Participants
|
166.4 cm
STANDARD_DEVIATION 12.6 • n=7 Participants
|
—
|
172.5 cm
STANDARD_DEVIATION 8.6 • n=4 Participants
|
171.7 cm
STANDARD_DEVIATION 8.34 • n=21 Participants
|
|
Weight
|
92.9 kg
STANDARD_DEVIATION 21.8 • n=5 Participants
|
102.4 kg
STANDARD_DEVIATION 29.2 • n=7 Participants
|
—
|
88.9 kg
STANDARD_DEVIATION 19.5 • n=4 Participants
|
92.5 kg
STANDARD_DEVIATION 20.4 • n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 5Population: The Pharmacokinetics Population consisted of participants in the safety population who had evaluable plasma PK samples for the estimation of Cmax or AUC (0-infinity).
AUC(0-infinity) was calculated by noncompartmental analysis using the linear up log down method with the area extrapolated to infinity as Clast/Lambda\_z where Clast was the last observed concentration and Lambda\_z is the elimination rate constant.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
AUC(0-infinity): Area Under the Concentration Time-curve Extrapolated to Infinity at Specified Pre-dose and Post-dose Time Points
|
34800 ng*hr/mL
Standard Deviation 10900
|
55900 ng*hr/mL
Standard Deviation 34100
|
—
|
30700 ng*hr/mL
Standard Deviation 6410
|
PRIMARY outcome
Timeframe: Day 1 to Day 5Population: The Pharmacokinetics Population consisted of participants in the safety population who had evaluable plasma PK samples for the estimation of Cmax or AUC (0-infinity).
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 was calculated by noncompartmental analysis using the linear up log down method.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
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
|
30800 ng*hr/mL
Standard Deviation 9860
|
47500 ng*hr/mL
Standard Deviation 26700
|
—
|
28400 ng*hr/mL
Standard Deviation 5130
|
PRIMARY outcome
Timeframe: Day 1 to Day 5Population: The Pharmacokinetics Population consisted of participants in the safety population who had evaluable plasma PK samples for the estimation of Cmax or AUC (0-infinity).
Apparent oral clearance was calculated by noncompartmental analysis using the formula Dose/AUC(0-infinity).
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
CL/F: Apparent Oral Clearance Calculated From Dose/AUC(0-infinifty) at Specified Pre-dose and Post-dose Time Points
|
6.6 L/hr
Standard Deviation 3.3
|
4.4 L/hr
Standard Deviation 2.7
|
—
|
6.8 L/hr
Standard Deviation 1.6
|
PRIMARY outcome
Timeframe: Day 1 to Day 5Population: The Pharmacokinetics Population consisted of participants in the safety population who had evaluable plasma PK samples for the estimation of Cmax or AUC (0-infinity).
Maximum Pretomanid concentration is the maximum observed drug concentration in blood plasma at specified pre-dose and post-dose timepoints.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Cmax: Maximum Pretomanid Concentration at Specified Pre-dose and Post-dose Time Points
|
866 ng/mL
Standard Deviation 391
|
1070 ng/mL
Standard Deviation 475
|
—
|
786 ng/mL
Standard Deviation 151
|
PRIMARY outcome
Timeframe: Day 1 to Day 5Population: The Pharmacokinetics Population consisted of participants in the safety population who had evaluable plasma PK samples for the estimation of Cmax or AUC (0-infinity).
Apparent terminal half-life at specified pre-dose and post-dose timepoints was estimated by ln(2)/Lambda\_z, where Lambda\_z is the elimination rate constant.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
t(1/2): Apparent Terminal Elimination Half-life at Specified Pre-dose and Post-dose Time Points
|
29.9 hr
Standard Deviation 8.1
|
33.6 hr
Standard Deviation 8.1
|
—
|
23.6 hr
Standard Deviation 8.2
|
PRIMARY outcome
Timeframe: Day 1 to Day 5Population: The Pharmacokinetics Population consisted of participants in the safety population who had evaluable plasma PK samples for the estimation of Cmax or AUC (0-infinity).
Time of maximum Pretomanid concentration (Tmax) at specified pre-dose and post-dose timepoints.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Tmax: Time of Maximum Pretomanid Concentration at Specified Pre-dose and Post-dose Time Points
|
3.2 hr
Standard Deviation 1.3
|
7.0 hr
Standard Deviation 7.1
|
—
|
5.7 hr
Standard Deviation 2.3
|
PRIMARY outcome
Timeframe: Day 1 to Day 5Population: The Pharmacokinetics Population consisted of participants in the safety population who had evaluable plasma PK samples for the estimation of Cmax or AUC (0-infinity).
Apparent Volume of Distribution at specified pre-dose and post-dose timepoints is the volume that the total amount of administered drug would occupy to provide the same concentration as it currently is in blood plasma divided by the bioavailability. It is calculated by Dose/\[Lambda\_z x AUC(0-infinity)\]
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Vd/F: Apparent Volume of Distribution at Specified Pre-dose and Post-dose Time Points
|
280.7 L
Standard Deviation 142.8
|
197.3 L
Standard Deviation 78.5
|
—
|
222.2 L
Standard Deviation 58.6
|
SECONDARY outcome
Timeframe: Day 1 to Day 12Population: The Safety Population included all participants who received study product.
Events were determined to be related if there was a reasonable possibility that the study product caused the adverse event (AE); that is, there was evidence to suggest a causal relationship between the study product and the AE. Each event was graded as mild, moderate or severe. Participants are counted according to their maximum severity of the event reported.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Incidence and Severity of Related Adverse Events
Mild
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Incidence and Severity of Related Adverse Events
Moderate
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Incidence and Severity of Related Adverse Events
Severe
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 12Population: The Safety Population included all participants who received study product.
A serious adverse event (SAE) is any adverse event occurring at any dose and regardless of causality that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, is a congenital anomaly or birth defect in an offspring of a subject taking study drug, or is an important medical event.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Incidence and Severity of Serious Adverse Events
Mild
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
|
Incidence and Severity of Serious Adverse Events
Moderate
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
|
Incidence and Severity of Serious Adverse Events
Severe
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 12Population: The Safety Population included all participants who received study product.
ECG data was collected, including PR interval, QRS duration, QT Interval, QTc interval, RR interval, and Ventricular rate. Abnormal ECG data was evaluated for clinical significance.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Number of Participants With Abnormal ECG Data
Clinically Significant
|
0 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal ECG Data
Not Clinically Significant
|
2 participants
|
0 participants
|
—
|
2 participants
|
|
Number of Participants With Abnormal ECG Data
No Events Reported
|
4 participants
|
0 participants
|
—
|
4 participants
|
SECONDARY outcome
Timeframe: Day 3, 4, 5 and 12Population: The Safety Population included all participants who received study product.
Summary of physical examination findings were obtained from a comprehensive physical examination including the following body system assessments: skin; head, eyes, ears, nose, and throat; thyroid; neurological; chest and lungs; cardiovascular; abdomen (liver and spleen); lymph nodes; musculoskeletal, and extremities.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Physical Exam Findings
Extremities
|
0 participants
|
1 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Pulmonary
|
1 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Skin
|
2 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Thyroid
|
0 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Neurological
|
0 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Chest and Lungs
|
0 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Cardiovascular
|
0 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Abdomen (liver and spleen)
|
0 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Lymph Nodes
|
0 participants
|
0 participants
|
—
|
0 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Head, Eyes, Ears, Nose, Throat
|
0 participants
|
0 participants
|
—
|
1 participants
|
|
Number of Participants With Abnormal Physical Exam Findings
Musculoskeletal
|
1 participants
|
0 participants
|
—
|
0 participants
|
SECONDARY outcome
Timeframe: Day 2, 5, and 12Population: The Safety Population included all participants who received study product.
Summary of abnormal laboratory parameters were collected following dose of study product through day 12. Abnormal findings were evaluated based on relationship to study product and clinical significance.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Albumin · No Events
|
6 Participants
|
1 Participants
|
0 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Aspartate Aminotransferase · No Events
|
6 Participants
|
2 Participants
|
0 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Blood Urea Nitrogen · Related, Not Clinically Significant
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Albumin · Related, Not Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Albumin · Not Related, Clinically Significant
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Aspartate Aminotransferase · Related, Not Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Aspartate Aminotransferase · Not Related, Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Blood Urea Nitrogen · Not Related, Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Blood Urea Nitrogen · No Events
|
5 Participants
|
2 Participants
|
0 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Calcium · Related, Not Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Calcium · Not Related, Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Calcium · No Events
|
6 Participants
|
2 Participants
|
0 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Creatinine · Related, Not Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Creatinine · Not Related, Clinically Significant
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Safety Laboratory Parameters
Creatinine · No Events
|
6 Participants
|
1 Participants
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, and 12Population: The Safety Population included all participants who received study product.
Vital signs were collected at each study visit following study product administration. Abnormal vital signs were graded as mild, moderate or severe.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 Participants
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 Participants
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs
Systolic Blood Pressure · Mild
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs
Pulse Rate · Severe
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs
Pulse Rate · None
|
5 Participants
|
2 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Vital Signs
Systolic Blood Pressure · Moderate
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs
Systolic Blood Pressure · Severe
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs
Systolic Blood Pressure · None
|
4 Participants
|
2 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Vital Signs
Diastolic Blood Pressure · Mild
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs
Diastolic Blood Pressure · Moderate
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs
Diastolic Blood Pressure · Severe
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs
Diastolic Blood Pressure · None
|
4 Participants
|
2 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Vital Signs
Pulse Rate · Mild
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Vital Signs
Pulse Rate · Moderate
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Severe Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Non-hepatically Impaired Controls
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Mild Hepatic Impairment
n=6 participants at risk
Participants with mild hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Moderate Hepatic Impairment
n=2 participants at risk
Participants with moderate hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
Non-hepatically Impaired Controls
n=6 participants at risk
Participants with no hepatic impairment received a single oral dose of 200mg Pretomanid tablets on day 1
|
|---|---|---|---|---|
|
Investigations
Blood pressure systolic decreased
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
Vascular disorders
Diastolic hypertension
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
Vascular disorders
Hypertension
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
General disorders
Infusion site bruising
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
50.0%
1/2 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
Cardiac disorders
Sinus bradycardia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
Vascular disorders
Systolic hypertension
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
|
General disorders
Vessel puncture site bruise
|
33.3%
2/6 • Number of events 2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/2 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
—
0/0 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
0.00%
0/6 • Adverse events were collected from the time of first dose of study drug until the final study visit on Day 12.
Within the severe hepatic impairment group, no participants were enrolled prior to study completion.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60