Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2009-014944-13 | EudraCT Number |
Not provided
Not provided
Not provided
The study was terminated early due to lack of efficacy after 10 participants enrolled.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is:
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Delamanid 250 mg BID+ OBR | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Delamanid | Drug | OPC-67683 film-coated tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs | 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. | Up to approximately 40 weeks |
| Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results | 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. | Up to approximately 40 weeks |
| Percentage of Participants With Potentially Clinically Significant Laboratory Values | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites | The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Infectology Center of Latvia - Clinic of Tuberculosis and Lung Diseases | Ogre | LV 5015 | Latvia | |||
| Hospital for Tuberculosis and Lung Diseases |
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims prespecified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
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.
Participants took part in the study at 3 investigative sites in Latvia and Lithuania from 19 February 2010 to 12 May 2011.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-treat (ITT) Population included all participants who took at least one dose of investigational medicinal product (IMP).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Delamanid 250 mg BID + OBR | 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. |
| BG001 | Delamanid 300 mg BID + OBR |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs | 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. | 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. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Delamanid 250 mg BID + OBR | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDra 11.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDra 11.1 | Systematic Assessment |
The trial was terminated per protocol for lack of efficacy and not for dose limiting toxicity (DLT).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Development | Otsuka Pharmaceutical Development & Commercialization, Inc. | 1-609-524-6788 | clinicaltransparency@otsuka-us.com |
Not provided
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D018088 | Tuberculosis, Multidrug-Resistant |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C516022 | OPC-67683 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Optimized Background Regimen (OBR) | Drug | OBR was selected at the discretion of the study investigator and included at least 2 anti-TB medications based on World Health Organization (WHO's) guidelines for the programmatic management of drug-resistant TB. Study investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results. |
|
| Up to approximately 40 weeks |
| Percentage of Participants With Abnormal Audiometry Assessment Values | Up to approximately 40 weeks |
| Percentage of Participants With Abnormal Visual Acuity Assessment Values | Up to approximately 40 weeks |
| Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial | Up to approximately 40 weeks |
| Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial | Up to approximately 40 weeks |
| Percentage of Participants With Adverse Events (AEs) | 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. | Up to approximately 40 weeks |
| Percentage of Participants With Immediately Reportable Events (IREs) | 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. | Up to approximately 40 weeks |
| Cmax: Maximal Peak Plasma Concentration for Delamanid | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid | AUC0-24h was calculated as 2×AUC0-12h. | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid | Ratio of accumulation for Cmax was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1. | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| Rac (AUC): Ratio of Accumulation for AUC of Delamanid | Ratio of accumulation for AUC was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1. | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. |
| At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites | The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| Rac (Cmax): Ratios of Accumulation for Cmax for Delamanid Metabolites | 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. | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| Rac (AUC): Ratios of Accumulation for AUC for Delamanid Metabolites | 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. | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
| Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168 | 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. | Day 168 (Week 24) |
| Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168 | 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. | Day 168 (Week 24) |
| Mean Change From Baseline in Time to Culture Positivity Using MGIT | 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. | Baseline and Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280 |
| Šiauliai |
| LT-76231 |
| Lithuania |
| National Tuberculosis and Infectious Diseases University Hospital | Vilnius | LT-10214 | Lithuania |
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.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
| Primary | Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results | 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. | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Percentage of Participants With Potentially Clinically Significant Laboratory Values | 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. | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Percentage of Participants With Abnormal Audiometry Assessment Values | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Percentage of Participants With Abnormal Visual Acuity Assessment Values | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Percentage of Participants With Adverse Events (AEs) | 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. | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Percentage of Participants With Immediately Reportable Events (IREs) | 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. | Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. | Posted | Number | percentage of participants | Up to approximately 40 weeks |
|
|
|
| Primary | Cmax: Maximal Peak Plasma Concentration for Delamanid | 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. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Primary | Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid | 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. | Posted | Median | Full Range | hours | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Primary | AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid | AUC0-24h was calculated as 2×AUC0-12h. | 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. | Posted | Mean | Standard Deviation | hour*nanograms per milliliter (h*ng/mL) | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Primary | Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid | Ratio of accumulation for Cmax was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1. | 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. | Posted | Mean | Standard Deviation | ratio | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Primary | Rac (AUC): Ratio of Accumulation for AUC of Delamanid | Ratio of accumulation for AUC was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1. | 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. | Posted | Mean | Standard Deviation | ratio | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Secondary | Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites | The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. | 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. | Posted | Mean | Standard Deviation | ng/mL | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Secondary | Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites | The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. | 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. | Posted | Median | Full Range | hours | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Secondary | AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites | The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. | 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. | Posted | Mean | Standard Deviation | h*ng/mL | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
|
| Secondary | Rac (Cmax): Ratios of Accumulation for Cmax for Delamanid Metabolites | 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. | Due to limited metabolite exposure on Day 1, the Rac for metabolites was not estimated and hence data was not collected for this endpoint. | Posted | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
| Secondary | Rac (AUC): Ratios of Accumulation for AUC for Delamanid Metabolites | 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. | Due to limited metabolite exposure on Day 1, the Rac for metabolites was not estimated and hence data was not collected for this endpoint. | Posted | At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196 |
|
|
| Secondary | Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168 | 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. | ITT Population included all participants who took at least one dose of IMP. | Posted | Number | percentage of participants | Day 168 (Week 24) |
|
|
|
| Secondary | Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168 | 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. | ITT Population included all participants who took at least one dose of IMP. | Posted | Number | percentage of participants | Day 168 (Week 24) |
|
|
|
| Secondary | Mean Change From Baseline in Time to Culture Positivity Using MGIT | 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. | 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. | Posted | Mean | Standard Deviation | days | Baseline and Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280 |
|
|
|
| 0 |
| 5 |
| 2 |
| 5 |
| 5 |
| 5 |
| EG001 | 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. | 1 | 5 | 2 | 5 | 5 | 5 |
| Acute myocardial infarction | Cardiac disorders | MedDra 11.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDra 11.1 | Systematic Assessment |
|
| Coronary artery disease | Cardiac disorders | MedDra 11.1 | Systematic Assessment |
|
| Tuberculosis | Infections and infestations | MedDra 11.1 | Systematic Assessment |
|
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDra 11.1 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDra 11.1 | Systematic Assessment |
|
| Alcohol abuse | Psychiatric disorders | MedDra 11.1 | Systematic Assessment |
|
| Lung lobectomy | Surgical and medical procedures | MedDra 11.1 | Systematic Assessment |
|
| Pneumonectomy | Surgical and medical procedures | MedDra 11.1 | Systematic Assessment |
|
| Atrioventricular block first degree | Cardiac disorders | MedDra 11.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDra 11.1 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDra 11.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDra 11.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDra 11.1 | Systematic Assessment |
|
| Feeling cold | General disorders | MedDra 11.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDra 11.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDra 11.1 | Systematic Assessment |
|
| Ulcer | General disorders | MedDra 11.1 | Systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDra 11.1 | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDra 11.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDra 11.1 | Systematic Assessment |
|
| Otitis media chronic | Infections and infestations | MedDra 11.1 | Systematic Assessment |
|
| Tuberculosis | Infections and infestations | MedDra 11.1 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDra 11.1 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDra 11.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDra 11.1 | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDra 11.1 | Systematic Assessment |
|
| Electrocardiogram ST-T change | Investigations | MedDra 11.1 | Systematic Assessment |
|
| Reticulocyte count increased | Investigations | MedDra 11.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDra 11.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDra 11.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDra 11.1 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDra 11.1 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDra 11.1 | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDra 11.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDra 11.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDra 11.1 | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDra 11.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDra 11.1 | Systematic Assessment |
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| Intercostal neuralgia | Nervous system disorders | MedDra 11.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDra 11.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDra 11.1 | Systematic Assessment |
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| Alcoholism | Psychiatric disorders | MedDra 11.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDra 11.1 | Systematic Assessment |
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| Hallucination | Psychiatric disorders | MedDra 11.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDra 11.1 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDra 11.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDra 11.1 | Systematic Assessment |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDra 11.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDra 11.1 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDra 11.1 | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDra 11.1 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDra 11.1 | Systematic Assessment |
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| Peripheral coldness | Vascular disorders | MedDra 11.1 | Systematic Assessment |
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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.
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| QTcB: New Onset (>500 msec) |
|
| QTcB: New Onset (>480 msec) |
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| QTcB: New Onset (>450 msec) |
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| QTcB: Change >=30, <=60 msec |
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| QTcF: New Onset (>500 msec) |
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| QTcF: New Onset (>480 msec) |
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| QTcF: New Onset (>450 msec) |
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| QTcF: Change >=30, <=60 msec |
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| ST Segment: New ST Segment Changes |
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| T Waves: New T Wave Changes |
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| Rhythm: New Abnormal Rhythm |
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| Conduction: New Conduction Changes |
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| Sodium (mEq/L) |
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| Triglycerides [milligrams per deciliter (mg/dL)] |
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| Uric acid (mg/dL) |
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| Lymphocytes [percentage (%)] |
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| Lymphocytes, Absolute [thousand cells per microliter (thous/µL)] |
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| Mean Corpuscular Volume [femtoliter (fL)] |
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| Neutrophils, Absolute (thous/µL) |
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| Platelet Count (thous/µL) |
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| Prothrombin Time [seconds (sec)] |
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| Red Blood Cell Count [million cells per microliter (mill/µL)] |
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| Reticulocyte Count (%) |
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| Participants Taking Antimycobacterials |
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| Participants Taking Analgesics |
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| Participants Taking Antidiarrheals, Intestinal Antiinflammatory |
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| Participants Taking Antiepileptics |
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| Participants Taking Antigout Preparations |
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| Participants Taking Antihemorrhagics |
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| Participants Taking Antihypertensives |
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| Participants Taking Antiinflammatory and Antirheumatic Products |
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| Participants Taking Antimycotics for Systemic Use |
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| Participants Taking Blood Substitutes and Perfusion Solutions |
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| Participants Taking Cardiac Therapy |
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| Participants Taking Corticosteroids for Systemic Use |
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| Participants Taking Cough and Cold Preparations |
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| Participants Taking Digestives, Including Enzymes |
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| Participants Taking Diuretics |
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| Participants Taking Drugs for Acid Related Disorders |
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| Participants Taking Drugs for Functional Gastrointestinal Disorders |
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| Participants Taking Drugs for Obstructive Airway Diseases |
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| Participants Taking Nasal Preparations |
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| Participants Taking Otologicals |
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| Participants Taking Psycholeptics |
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| Participants Taking Unspecified Herbal and Traditional Medicine |
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| Participants Taking Vasoprotectives |
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| Participants Taking Vitamins |
|
| Day 14 |
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| Day 28 |
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| Day 56 |
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| Day 112 |
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| Day 196 |
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| Day 14 |
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| Day 28 |
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| Day 56 |
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| Day 112 |
|
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| Day 196 |
|
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| Day 14 |
|
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| Day 28 |
|
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| Day 56 |
|
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| Day 112 |
|
|
| Day 196 |
|
|
|
| Day 28 |
|
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| Day 56 |
|
|
| Day 112 |
|
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| Day 196 |
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|
|
| Day 28 |
|
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| Day 56 |
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| Day 112 |
|
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| Day 196 |
|
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| DM-6704: Cmax at Day 14 |
|
|
| DM-6704: Cmax at Day 28 |
|
|
| DM-6704: Cmax at Day 56 |
|
|
| DM-6704: Cmax at Day 112 |
|
|
| DM-6704: Cmax at Day 196 |
|
|
| DM-6705: Cmax at Day 1 |
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| DM-6705: Cmax at Day 14 |
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| DM-6705: Cmax at Day 28 |
|
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| DM-6705: Cmax at Day 56 |
|
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| DM-6705: Cmax at Day 112 |
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|
| DM-6705: Cmax at Day 196 |
|
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| DM-6706: Cmax at Day 1 |
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| DM-6706: Cmax at Day 14 |
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| DM-6706: Cmax at Day 28 |
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| DM-6706: Cmax at Day 56 |
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| DM-6706: Cmax at Day 112 |
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| DM-6706: Cmax at Day 196 |
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| DM-6704: Tmax at Day 14 |
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| DM-6704: Tmax at Day 28 |
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| DM-6704: Tmax at Day 56 |
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| DM-6704: Tmax at Day 112 |
|
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| DM-6704: Tmax at Day 196 |
|
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| DM-6705: Tmax at Day 1 |
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| DM-6705: Tmax at Day 14 |
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| DM-6705: Tmax at Day 28 |
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| DM-6705: Tmax at Day 56 |
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| DM-6705: Tmax at Day 112 |
|
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| DM-6705: Tmax at Day 196 |
|
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| DM-6706: Tmax at Day 1 |
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| DM-6706: Tmax at Day 14 |
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| DM-6706: Tmax at Day 28 |
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| DM-6706: Tmax at Day 56 |
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| DM-6706: Tmax at Day 112 |
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| DM-6706: Tmax at Day 196 |
|
|
| DM-6704: AUC0-24h at Day 14 |
|
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| DM-6704: AUC0-24h at Day 28 |
|
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| DM-6704: AUC0-24h at Day 56 |
|
|
| DM-6704: AUC0-24h at Day 112 |
|
|
| DM-6704: AUC0-24h at Day 196 |
|
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| DM-6705: AUC0-24h at Day 1 |
|
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| DM-6705: AUC0-24h at Day 14 |
|
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| DM-6705: AUC0-24h at Day 28 |
|
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| DM-6705: AUC0-24h at Day 56 |
|
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| DM-6705: AUC0-24h at Day 112 |
|
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| DM-6705: AUC0-24h at Day 196 |
|
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| DM-6706: AUC0-24h at Day 1 |
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| DM-6706: AUC0-24h at Day 14 |
|
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| DM-6706: AUC0-24h at Day 28 |
|
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| DM-6706: AUC0-24h at Day 56 |
|
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| DM-6706: AUC0-24h at Day 112 |
|
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| DM-6706: AUC0-24h at Day 196 |
|
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| Change from Baseline at Day 7 |
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| Change from Baseline at Day 14 |
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| Change from Baseline at Day 21 |
|
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| Change from Baseline at Day 28 |
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| Change from Baseline at Day 35 |
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| Change from Baseline at Day 42 |
|
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| Change from Baseline at Day 49 |
|
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| Change from Baseline at Day 56 |
|
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| Change from Baseline at Day 70 |
|
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| Change from Baseline at Day 84 |
|
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| Change from Baseline at Day 98 |
|
|
| Change from Baseline at Day 112 |
|
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| Change from Baseline at Day 126 |
|
|
| Change from Baseline at Day 140 |
|
|
| Change from Baseline at Day 154 |
|
|
| Change from Baseline at Day 168 |
|
|
| Change from Baseline at Day 182 |
|
|
| Change from Baseline at Day 196 |
|
|
| Change from Baseline at Day 224 |
|
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| Change from Baseline at Day 252 |
|
|
| Change from Baseline at Day 280 |
|
|