Trial Outcomes & Findings for Safety and Pharmacokinetics (PK) in Multidrug-Resistant (MDR) Refractive Tuberculosis (NCT NCT01131351)
NCT ID: NCT01131351
Last Updated: 2021-11-11
Results Overview
Vital signs included body weight \[kilogram (kg)\], body temperature \[degree Celsius (°C)\], heart rate \[beats per minute (BPM)\], respiratory rate (breaths/minute), systolic and diastolic blood pressure \[millimeter of mercury (mmHg)\]. The criteria for clinically significant abnormal value were: body weight (kg): increase \>=5% or decrease \>=5%; body temperature (°C): \>=38.5°C and increase of \>=1.1°C; heart rate (BPM): \>=120 bpm and increase of \>=15 bpm, or \<=60 bpm and decrease of \>=15 bpm; systolic blood pressure (mmHg): \>=160 mmHg and increase of \>=20 mmHg, or \<=90 mmHg and decrease of \>=20 mmHg; diastolic blood pressure (mmHg): \>=105 mmHg and increase of \>=15 mmHg, or \<=50 mmHg and decrease of \>=15 mmHg; respiration rate (breaths per minute) \>30 breaths per minute. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
Up to approximately 40 weeks
Results posted on
2021-11-11
Participant Flow
Participants took part in the study at 3 investigative sites in Latvia and Lithuania from 19 February 2010 to 12 May 2011.
A total of 10 participants received at least one dose of delamanid (5 participants in delamanid 250 mg BID+ OBR group and 5 participants in delamanid 300 mg BID+ OBR group). Of which, 7 participants completed the study.
Participant milestones
| Measure |
Delamanid 250 mg BID + OBR
Participants received delamanid five 50 milligrams (mg) (250 mg) tablets, twice a day (BID), along with at least 2 additional anti-TB medications per optimized background regimen (OBR) for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
|
Overall Study
COMPLETED
|
5
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Delamanid 250 mg BID + OBR
Participants received delamanid five 50 milligrams (mg) (250 mg) tablets, twice a day (BID), along with at least 2 additional anti-TB medications per optimized background regimen (OBR) for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Protocol Deviation
|
0
|
1
|
Baseline Characteristics
Safety and Pharmacokinetics (PK) in Multidrug-Resistant (MDR) Refractive Tuberculosis
Baseline characteristics by cohort
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.6 years
STANDARD_DEVIATION 10.8 • n=93 Participants
|
34.0 years
STANDARD_DEVIATION 12.5 • n=4 Participants
|
40.3 years
STANDARD_DEVIATION 12.9 • n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. Number analyzed is the number of participants who had at least one post-baseline numerical result for the given test. Baseline was defined as the last measurements prior to the first dosing of study medication.
Vital signs included body weight \[kilogram (kg)\], body temperature \[degree Celsius (°C)\], heart rate \[beats per minute (BPM)\], respiratory rate (breaths/minute), systolic and diastolic blood pressure \[millimeter of mercury (mmHg)\]. The criteria for clinically significant abnormal value were: body weight (kg): increase \>=5% or decrease \>=5%; body temperature (°C): \>=38.5°C and increase of \>=1.1°C; heart rate (BPM): \>=120 bpm and increase of \>=15 bpm, or \<=60 bpm and decrease of \>=15 bpm; systolic blood pressure (mmHg): \>=160 mmHg and increase of \>=20 mmHg, or \<=90 mmHg and decrease of \>=20 mmHg; diastolic blood pressure (mmHg): \>=105 mmHg and increase of \>=15 mmHg, or \<=50 mmHg and decrease of \>=15 mmHg; respiration rate (breaths per minute) \>30 breaths per minute. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Heart Rate: <=60 bpm + Decrease of >=15 bpm
|
40.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Weight: Decrease of >=5% in Body Weight
|
60.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Weight: Increase of >=5% in Body Weight
|
20.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Systolic Blood Pressure: <= 90 mmHg + Decrease of >=20 mmHg
|
40.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Respiration Rate: >30 Breaths Per Minute
|
20.0 percentage of participants
|
0.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
The criteria for clinically significant abnormal ECG values were- ventricular rate outlier (\<50 bpm and decrease of \>=25%, \>100 bpm and increase of \>=25%), PR outlier \[increase of \>=25% when PR \>200 milliseconds (ms)\], QRS outlier (increase of \>=25% when QRS \>100 ms), QT (new onset (in treatment period but not at Baseline) \[\>500 ms\]), QT interval corrected by Bazett's formula (QTcB) (new onset \[\>450, \>480, \>500 ms\], increase of \>=30 ms and \<= 60 ms or increase of \>60 ms), QT interval corrected by Fridericia's formula (QTcF) (new onset \[\>450, \>480, \>500 ms\], increase of \>=30 ms and \<= 60 ms or increase of \>60 ms), new abnormal U waves, new ST segment changes, new T wave changes, new abnormal rhythm, new conduction abnormality were reported as categories. Baseline was defined as the average of the ECGs taken at Day -1. Only categories with data for potentially clinically significant abnormal ECG values are reported.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
Vent Rate Outliers: Notable Decreases
|
40.00 percentage of participants
|
0.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
Vent Rate Outliers: Notable Increases
|
40.00 percentage of participants
|
0.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcB: New Onset (>500 msec)
|
0.00 percentage of participants
|
20.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcB: New Onset (>480 msec)
|
0.00 percentage of participants
|
40.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcB: New Onset (>450 msec)
|
40.00 percentage of participants
|
40.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcB: Change >=30, <=60 msec
|
40.00 percentage of participants
|
80.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcF: New Onset (>500 msec)
|
0.00 percentage of participants
|
20.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcF: New Onset (>480 msec)
|
0.00 percentage of participants
|
20.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcF: New Onset (>450 msec)
|
0.00 percentage of participants
|
40.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
QTcF: Change >=30, <=60 msec
|
60.00 percentage of participants
|
80.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
ST Segment: New ST Segment Changes
|
0.00 percentage of participants
|
20.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
T Waves: New T Wave Changes
|
20.00 percentage of participants
|
20.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
Rhythm: New Abnormal Rhythm
|
60.00 percentage of participants
|
80.00 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
Conduction: New Conduction Changes
|
0.00 percentage of participants
|
40.00 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
Clinical laboratory tests included hematology, coagulation, chemistry, and urinalysis. The participants were categorized based on the clinically significant laboratory values as per protocol predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for laboratory assessments are reported.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Lactic Dehydrogenase [units per liter (U/L)]
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Potassium [milliequivalents per liter (mEq/L)]
|
60.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Sodium (mEq/L)
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Triglycerides [milligrams per deciliter (mg/dL)]
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Uric acid (mg/dL)
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Lymphocytes [percentage (%)]
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Lymphocytes, Absolute [thousand cells per microliter (thous/µL)]
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Mean Corpuscular Volume [femtoliter (fL)]
|
20.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Neutrophils, Absolute (thous/µL)
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Platelet Count (thous/µL)
|
20.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Prothrombin Time [seconds (sec)]
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Red Blood Cell Count [million cells per microliter (mill/µL)]
|
20.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant Laboratory Values
Reticulocyte Count (%)
|
60.0 percentage of participants
|
60.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Abnormal Audiometry Assessment Values
|
100.0 percentage of participants
|
80.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Abnormal Visual Acuity Assessment Values
|
40.0 percentage of participants
|
20.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial
Total Participants Using One or More Medications
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial
Participants Taking Antibacterials for Systemic Use
|
80.0 percentage of participants
|
80.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial
Participants Taking Antimycobacterials
|
100.0 percentage of participants
|
100.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Diuretics
|
40.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Total Participants Using One or More Medications
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Agents Acting on the Renin-Angiotensin System
|
20.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Analgesics
|
40.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Antidiarrheals, Intestinal Antiinflammatory
|
20.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Antiepileptics
|
20.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Antigout Preparations
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Antihemorrhagics
|
20.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Antihypertensives
|
20.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Antiinflammatory and Antirheumatic Products
|
60.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Antimycotics for Systemic Use
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Blood Substitutes and Perfusion Solutions
|
40.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Cardiac Therapy
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Corticosteroids for Systemic Use
|
0.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Cough and Cold Preparations
|
60.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Digestives, Including Enzymes
|
80.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Drugs for Acid Related Disorders
|
80.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Drugs for Functional Gastrointestinal Disorders
|
60.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Drugs for Obstructive Airway Diseases
|
40.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Nasal Preparations
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Otologicals
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Psycholeptics
|
60.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Unspecified Herbal and Traditional Medicine
|
40.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Vasoprotectives
|
20.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial
Participants Taking Vitamins
|
0.0 percentage of participants
|
60.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the investigator.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
|
100.0 percentage of participants
|
100.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to approximately 40 weeksPopulation: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-participant hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above. The following were considered as IREs- serious adverse events (SAEs), pregnancies in trial participants or their partners, and all events involving overdose, misuse and abuse.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Immediately Reportable Events (IREs)
|
40.0 percentage of participants
|
40.0 percentage of participants
|
PRIMARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: Intent-to-treat (ITT) Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid
Day 1
|
142 nanograms per milliliter (ng/mL)
Standard Deviation 68.2
|
192 nanograms per milliliter (ng/mL)
Standard Deviation 93.5
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid
Day 14
|
521 nanograms per milliliter (ng/mL)
Standard Deviation 132
|
514 nanograms per milliliter (ng/mL)
Standard Deviation 99.3
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid
Day 28
|
558 nanograms per milliliter (ng/mL)
Standard Deviation 113
|
573 nanograms per milliliter (ng/mL)
Standard Deviation 117
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid
Day 56
|
558 nanograms per milliliter (ng/mL)
Standard Deviation 239
|
503 nanograms per milliliter (ng/mL)
Standard Deviation 126
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid
Day 112
|
441 nanograms per milliliter (ng/mL)
Standard Deviation 286
|
427 nanograms per milliliter (ng/mL)
Standard Deviation 114
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid
Day 196
|
494 nanograms per milliliter (ng/mL)
Standard Deviation 129
|
499 nanograms per milliliter (ng/mL)
Standard Deviation 241
|
PRIMARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid
Day 196
|
2.95 hours
Interval 0.0 to 8.95
|
3.00 hours
Interval 3.0 to 3.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid
Day 1
|
2.95 hours
Interval 2.95 to 12.15
|
3.20 hours
Interval 3.0 to 11.88
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid
Day 14
|
2.95 hours
Interval 0.0 to 3.27
|
3.02 hours
Interval 2.53 to 3.05
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid
Day 28
|
2.95 hours
Interval 2.95 to 3.0
|
3.03 hours
Interval 3.0 to 8.92
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid
Day 56
|
2.95 hours
Interval 0.0 to 8.95
|
3.00 hours
Interval 3.0 to 8.97
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid
Day 112
|
2.95 hours
Interval 0.0 to 3.0
|
3.03 hours
Interval 3.0 to 3.05
|
PRIMARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
AUC0-24h was calculated as 2×AUC0-12h.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid
Day 1
|
2020 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 708
|
2650 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 1280
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid
Day 14
|
9580 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 2790
|
10400 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 1950
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid
Day 28
|
9840 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 3090
|
11200 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 2450
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid
Day 56
|
10500 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 4490
|
9720 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 2400
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid
Day 112
|
8020 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 5470
|
8470 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 3080
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid
Day 196
|
9420 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 2340
|
8640 hour*nanograms per milliliter (h*ng/mL)
Standard Deviation 2890
|
PRIMARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
Ratio of accumulation for Cmax was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid
Day 196
|
3.80 ratio
Standard Deviation 1.25
|
1.93 ratio
Standard Deviation 0.418
|
|
Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid
Day 14
|
4.01 ratio
Standard Deviation 1.22
|
3.76 ratio
Standard Deviation 3.13
|
|
Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid
Day 28
|
4.33 ratio
Standard Deviation 1.31
|
4.01 ratio
Standard Deviation 2.84
|
|
Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid
Day 56
|
4.04 ratio
Standard Deviation 0.657
|
3.24 ratio
Standard Deviation 1.71
|
|
Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid
Day 112
|
3.07 ratio
Standard Deviation 1.25
|
1.89 ratio
Standard Deviation 0.485
|
PRIMARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
Ratio of accumulation for AUC was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Rac (AUC): Ratio of Accumulation for AUC of Delamanid
Day 14
|
4.85 ratio
Standard Deviation 0.938
|
5.45 ratio
Standard Deviation 4.38
|
|
Rac (AUC): Ratio of Accumulation for AUC of Delamanid
Day 28
|
4.92 ratio
Standard Deviation 0.699
|
5.66 ratio
Standard Deviation 4.18
|
|
Rac (AUC): Ratio of Accumulation for AUC of Delamanid
Day 56
|
5.13 ratio
Standard Deviation 0.762
|
4.55 ratio
Standard Deviation 2.45
|
|
Rac (AUC): Ratio of Accumulation for AUC of Delamanid
Day 112
|
3.74 ratio
Standard Deviation 1.47
|
2.85 ratio
Standard Deviation 1.27
|
|
Rac (AUC): Ratio of Accumulation for AUC of Delamanid
Day 196
|
4.79 ratio
Standard Deviation 0.800
|
2.29 ratio
Standard Deviation 0.367
|
SECONDARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Cmax at Day 1
|
1.33 ng/mL
Standard Deviation 0.257
|
2.53 ng/mL
Standard Deviation 1.59
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Cmax at Day 14
|
43.1 ng/mL
Standard Deviation 25.2
|
82.7 ng/mL
Standard Deviation 32.8
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Cmax at Day 28
|
52.5 ng/mL
Standard Deviation 12.8
|
95.9 ng/mL
Standard Deviation 31.5
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Cmax at Day 56
|
59.9 ng/mL
Standard Deviation 22.4
|
119 ng/mL
Standard Deviation 79.6
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Cmax at Day 112
|
58.5 ng/mL
Standard Deviation 33.8
|
88.8 ng/mL
Standard Deviation 67.3
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Cmax at Day 196
|
71.2 ng/mL
Standard Deviation 8.85
|
99.3 ng/mL
Standard Deviation 104
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Cmax at Day 1
|
2.88 ng/mL
Standard Deviation 1.41
|
3.75 ng/mL
Standard Deviation 1.79
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Cmax at Day 14
|
76.6 ng/mL
Standard Deviation 25.4
|
95.4 ng/mL
Standard Deviation 30.1
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Cmax at Day 28
|
114 ng/mL
Standard Deviation 47.8
|
146 ng/mL
Standard Deviation 58.8
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Cmax at Day 56
|
140 ng/mL
Standard Deviation 64.2
|
142 ng/mL
Standard Deviation 50.1
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Cmax at Day 112
|
128 ng/mL
Standard Deviation 85.0
|
126 ng/mL
Standard Deviation 80.2
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Cmax at Day 196
|
135 ng/mL
Standard Deviation 62.9
|
154 ng/mL
Standard Deviation 128
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Cmax at Day 14
|
44.6 ng/mL
Standard Deviation 24.1
|
71.9 ng/mL
Standard Deviation 23.1
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Cmax at Day 28
|
64.0 ng/mL
Standard Deviation 27.9
|
97.7 ng/mL
Standard Deviation 23.0
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Cmax at Day 56
|
77.6 ng/mL
Standard Deviation 28.4
|
103 ng/mL
Standard Deviation 72.2
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Cmax at Day 112
|
75.2 ng/mL
Standard Deviation 36.5
|
83.1 ng/mL
Standard Deviation 54.7
|
|
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Cmax at Day 196
|
81.7 ng/mL
Standard Deviation 6.38
|
94.9 ng/mL
Standard Deviation 92.1
|
SECONDARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Tmax at Day 1
|
11.95 hours
Interval 8.95 to 12.15
|
12.00 hours
Interval 11.88 to 12.25
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Tmax at Day 14
|
2.95 hours
Interval 0.0 to 12.12
|
3.02 hours
Interval 0.0 to 12.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Tmax at Day 28
|
2.95 hours
Interval 0.0 to 2.95
|
3.00 hours
Interval 0.0 to 8.92
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Tmax at Day 56
|
5.95 hours
Interval 0.0 to 8.95
|
3.00 hours
Interval 0.0 to 9.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Tmax at Day 112
|
0.00 hours
Interval 0.0 to 11.95
|
0.00 hours
Interval 0.0 to 9.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6704: Tmax at Day 196
|
2.95 hours
Interval 0.0 to 8.95
|
3.00 hours
Interval 3.0 to 3.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Tmax at Day 1
|
5.95 hours
Interval 2.95 to 12.15
|
5.92 hours
Interval 3.0 to 12.25
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Tmax at Day 14
|
5.95 hours
Interval 0.0 to 11.95
|
9.00 hours
Interval 3.02 to 11.53
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Tmax at Day 28
|
2.95 hours
Interval 2.95 to 5.95
|
6.00 hours
Interval 3.03 to 8.92
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Tmax at Day 56
|
5.95 hours
Interval 2.95 to 9.0
|
8.97 hours
Interval 0.0 to 12.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Tmax at Day 112
|
2.95 hours
Interval 0.0 to 8.95
|
3.00 hours
Interval 0.0 to 6.03
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6705: Tmax at Day 196
|
5.95 hours
Interval 2.95 to 12.0
|
7.49 hours
Interval 6.0 to 8.98
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Tmax at Day 14
|
8.95 hours
Interval 0.0 to 12.12
|
0.00 hours
Interval 0.0 to 5.97
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Tmax at Day 28
|
2.95 hours
Interval 2.95 to 12.0
|
3.00 hours
Interval 0.0 to 8.92
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Tmax at Day 56
|
5.95 hours
Interval 0.0 to 8.95
|
0.00 hours
Interval 0.0 to 9.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Tmax at Day 112
|
0.00 hours
Interval 0.0 to 0.0
|
0.00 hours
Interval 0.0 to 12.0
|
|
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites
DM-6706: Tmax at Day 196
|
8.95 hours
Interval 2.95 to 8.98
|
6.01 hours
Interval 3.0 to 9.02
|
SECONDARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6704: AUC0-24h at Day 1
|
11.1 h*ng/mL
Standard Deviation NA
The standard deviation was not estimable due to fewer number of participants with data available for analysis.
|
19.2 h*ng/mL
Standard Deviation NA
The standard deviation was not estimable due to fewer number of participants with data available for analysis.
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6704: AUC0-24h at Day 14
|
928 h*ng/mL
Standard Deviation 567
|
1830 h*ng/mL
Standard Deviation 705
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6704: AUC0-24h at Day 28
|
1140 h*ng/mL
Standard Deviation 357
|
2100 h*ng/mL
Standard Deviation 666
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6704: AUC0-24h at Day 56
|
1280 h*ng/mL
Standard Deviation 499
|
2610 h*ng/mL
Standard Deviation 1760
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6704: AUC0-24h at Day 112
|
1220 h*ng/mL
Standard Deviation 711
|
1820 h*ng/mL
Standard Deviation 1250
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6704: AUC0-24h at Day 196
|
1550 h*ng/mL
Standard Deviation 176
|
2130 h*ng/mL
Standard Deviation 2230
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6705: AUC0-24h at Day 1
|
45.5 h*ng/mL
Standard Deviation 13.6
|
64.8 h*ng/mL
Standard Deviation 11.5
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6705: AUC0-24h at Day 14
|
1650 h*ng/mL
Standard Deviation 543
|
2070 h*ng/mL
Standard Deviation 593
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6705: AUC0-24h at Day 28
|
2500 h*ng/mL
Standard Deviation 1110
|
3140 h*ng/mL
Standard Deviation 1140
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6705: AUC0-24h at Day 56
|
3100 h*ng/mL
Standard Deviation 1480
|
3150 h*ng/mL
Standard Deviation 1130
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6705: AUC0-24h at Day 112
|
2790 h*ng/mL
Standard Deviation 1800
|
2710 h*ng/mL
Standard Deviation 1500
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6705: AUC0-24h at Day 196
|
3060 h*ng/mL
Standard Deviation 1410
|
3440 h*ng/mL
Standard Deviation 2890
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6706: AUC0-24h at Day 14
|
966 h*ng/mL
Standard Deviation 531
|
1590 h*ng/mL
Standard Deviation 496
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6706: AUC0-24h at Day 28
|
1430 h*ng/mL
Standard Deviation 668
|
2190 h*ng/mL
Standard Deviation 498
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6706: AUC0-24h at Day 56
|
1670 h*ng/mL
Standard Deviation 608
|
2290 h*ng/mL
Standard Deviation 1650
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6706: AUC0-24h at Day 112
|
1630 h*ng/mL
Standard Deviation 815
|
1760 h*ng/mL
Standard Deviation 1050
|
|
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites
DM-6706: AUC0-24h at Day 196
|
1820 h*ng/mL
Standard Deviation 188
|
2060 h*ng/mL
Standard Deviation 2060
|
SECONDARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: Due to limited metabolite exposure on Day 1, the Rac for metabolites was not estimated and hence data was not collected for this endpoint.
The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. Ratio of accumulation for Cmax was planned to be assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196Population: Due to limited metabolite exposure on Day 1, the Rac for metabolites was not estimated and hence data was not collected for this endpoint.
The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. Ratio of accumulation for AUC was planned to be assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1. Limited metabolite exposure on Day 1 did not allow for estimation of Rac for metabolites.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 168 (Week 24)Population: ITT Population included all participants who took at least one dose of IMP.
Sputum culture conversion was evaluated using the MGIT culture system. A participant was classified as demonstrating a sputum culture conversion if he/she achieved two consecutive sputum cultures negative for growth of Mycobacterium tuberculosis at least 28 days apart after his/her last sputum culture positive for growth and not followed by any sputum specimens positive for growth.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168
|
0.0 percentage of participants
|
20.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 168 (Week 24)Population: ITT Population included all participants who took at least one dose of IMP.
Sputum culture status was determined using solid mycobacterial culture media and measuring colony counts per milliliter of sputum. The unit for colony counts: log10 colony-forming unit (CFU)/mL. A participant was classified as demonstrating a sputum culture conversion if he/she achieved two consecutive sputum cultures negative for growth of Mycobacterium tuberculosis at least 28 days apart after his/her last sputum culture positive for growth and not followed by any sputum specimens positive for growth.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168
|
0.0 percentage of participants
|
20.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.
The value for time to positivity was defined (in days) as the time interval from inoculation until a positive signal was detected for MTB on sputum culture in the MGIT system during the routine 42 day incubation period. Time to positivity analysis was based on the corresponding qualitative sputum results of positive and negative sputum cultures in days of the initial positive signal for a culture from the MGIT system. Mean is reported for Baseline and mean change from baseline is reported for Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280. Baseline is Day -2 and -1. Mean time to culture positivity at Baseline was defined as the average of Day -2 and Day -1 values, if the cultures on both days were positive; and if only one culture was positive, the value for the positive culture was used as baseline.
Outcome measures
| Measure |
Delamanid 250 mg BID + OBR
n=5 Participants
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 Participants
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Baseline
|
7.7 days
Standard Deviation 3.7
|
6.8 days
Standard Deviation 1.6
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 7
|
6.8 days
Standard Deviation 12.2
|
3.5 days
Standard Deviation 2.9
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 14
|
0.7 days
Standard Deviation 1.0
|
1.7 days
Standard Deviation 1.4
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 21
|
2.6 days
Standard Deviation 0.9
|
2.1 days
Standard Deviation 2.0
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 28
|
0.9 days
Standard Deviation 2.7
|
2.1 days
Standard Deviation 2.5
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 35
|
8.8 days
Standard Deviation 11.1
|
11.1 days
Standard Deviation 15.1
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 42
|
6.4 days
Standard Deviation 8.7
|
6.3 days
Standard Deviation 9.9
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 49
|
0.8 days
Standard Deviation 2.6
|
9.1 days
Standard Deviation 16.4
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 56
|
7.3 days
Standard Deviation 11.9
|
5.8 days
Standard Deviation 7.6
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 70
|
7.7 days
Standard Deviation 11.9
|
16.4 days
Standard Deviation 16.9
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 84
|
10.5 days
Standard Deviation 12.4
|
12.1 days
Standard Deviation 16.2
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 98
|
3.4 days
Standard Deviation 3.9
|
9.8 days
Standard Deviation 16.5
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 112
|
3.8 days
Standard Deviation 7.0
|
10.7 days
Standard Deviation 20.0
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 126
|
-0.8 days
Standard Deviation 2.9
|
0.1 days
Standard Deviation 1.9
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 140
|
1.5 days
Standard Deviation 5.4
|
17.3 days
Standard Deviation 25.2
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 154
|
0.8 days
Standard Deviation 2.1
|
8.3 days
Standard Deviation 17.0
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 168
|
-0.8 days
Standard Deviation 4.5
|
17.3 days
Standard Deviation 23.2
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 182
|
-2.5 days
Standard Deviation 3.0
|
16.5 days
Standard Deviation 24.4
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 196
|
-0.6 days
Standard Deviation 3.9
|
20.9 days
Standard Deviation 18.1
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 224
|
1.6 days
Standard Deviation 4.6
|
16.2 days
Standard Deviation 24.8
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 252
|
9.1 days
Standard Deviation 12.0
|
16.5 days
Standard Deviation 24.4
|
|
Mean Change From Baseline in Time to Culture Positivity Using MGIT
Change from Baseline at Day 280
|
20.3 days
Standard Deviation 19.0
|
16.6 days
Standard Deviation 24.2
|
Adverse Events
Delamanid 250 mg BID + OBR
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Delamanid 300 mg BID + OBR
Serious events: 2 serious events
Other events: 5 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Delamanid 250 mg BID + OBR
n=5 participants at risk
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 participants at risk
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Infections and infestations
Tuberculosis
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Psychiatric disorders
Alcohol abuse
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Surgical and medical procedures
Lung lobectomy
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Surgical and medical procedures
Pneumonectomy
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
Other adverse events
| Measure |
Delamanid 250 mg BID + OBR
n=5 participants at risk
Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
Delamanid 300 mg BID + OBR
n=5 participants at risk
Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Abdominal distension
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Dyspepsia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Nausea
|
60.0%
3/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Toothache
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Gastrointestinal disorders
Vomiting
|
60.0%
3/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
General disorders
Chest pain
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
General disorders
Feeling cold
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
General disorders
Oedema peripheral
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
General disorders
Pyrexia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
General disorders
Ulcer
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Hepatobiliary disorders
Hepatic pain
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Hepatobiliary disorders
Hepatomegaly
|
60.0%
3/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Infections and infestations
Otitis media chronic
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Infections and infestations
Tuberculosis
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
60.0%
3/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Infections and infestations
Viral infection
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
60.0%
3/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Investigations
Blood potassium increased
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Investigations
Electrocardiogram ST-T change
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Investigations
Reticulocyte count increased
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Investigations
Weight decreased
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
60.0%
3/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
80.0%
4/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Nervous system disorders
Headache
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Nervous system disorders
Intercostal neuralgia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Nervous system disorders
Paraesthesia
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Nervous system disorders
Syncope
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Psychiatric disorders
Alcoholism
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Psychiatric disorders
Anxiety
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Psychiatric disorders
Hallucination
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Psychiatric disorders
Insomnia
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Renal and urinary disorders
Proteinuria
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
40.0%
2/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
60.0%
3/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Skin and subcutaneous tissue disorders
Acne
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
|
Vascular disorders
Peripheral coldness
|
20.0%
1/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
0.00%
0/5 • From first dose of study drug through end of study (Up to approximately 40 weeks)
Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 1-609-524-6788
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
- Publication restrictions are in place
Restriction type: OTHER