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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-005107-26 | EudraCT Number |
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A phase 2, multicenter, uncontrolled, open-label trial in participants with Multi-drug Resistant Tuberculosis (MDR-TB). Only participants who completed Trial 242-07-204 (NCT00685360) were eligible. The trial was performed globally at 14 sites qualified to treat MDR-TB. All 434 participants who completed Trial 242-07-204 were eligible for this trial if there was still potential clinical benefit to them and all inclusion criteria and no exclusion criteria were met.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Delamanid 100 mg BID + OBR | Experimental | Participants received Delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) along with at least 4 additional anti-TB medications per optimized background regimen (OBR) from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. |
|
| Delamanid 200 mg BID + OBR | Experimental | Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Delamanid | Drug | Delamanid was administered orally twice daily as 50-mg tablets under fed conditions in the morning and evening. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinically Significant Abnormality in Vital Signs | Vital signs included weight (kg), body temperature (degree Celsius), heart rate [beats/minute (bpm)], systolic and diastolic blood pressure [millimetre of mercury (mm Hg)]. The criteria for clinically significant abnormal value for: weight was decrease or increase of >=5% in body weight, heart rate was <=60 bpm and decrease of >=15 bpm; >=120 bpm and Increase of >=15 bpm, systolic blood pressure (SBP) <=90 mm Hg and decrease of >=20 mm Hg; diastolic blood pressure (DBP) <=50 mm Hg and decrease of >=15 mm Hg, all vital signs relative to Baseline. Baseline is Study 204 completion visit (Day 84) for participants who complete the baseline visit within 7 days of completing Study 204. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported. | From first dose of study drug up to Week 26 |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values | 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. Only categories with data are reported. | From first dose of study drug up to Week 26 |
| Number of Participants With Clinical Significant Abnormality in Laboratory Test | Laboratory assessments included parameters for serum chemistry (alkaline phosphatase, alanine aminotransferase, alanine transaminase, total bilirubin, cholesterol, gamma-glutamyl transferase, glucose, lactic dehydrogenase, potassium, sodium, triglycerides, uric acid), hematology (white blood cell count eosinophils, absolute, hematocrit, hemoglobin, lymphocytes, absolute, mean corpuscular volume, neutrophil, bands, neutrophils, neutrophils, absolute, platelet count, red blood cell (RBC) count, reticulocyte count) and urinalysis (blood, epithelial cast, granular cast, hyaline cast, RBCs per high power field (RBC/HPF)). The participants were categorized based on the clinically significant laboratory values as per 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 |
|---|---|---|
| Percentage of Treatment Responders Using the Mycobacterial Growth Indicator Tube (MGIT) Culture System | Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with sputum culture conversion (SCC) at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis (MTB) at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Chest Hospital | Beijing | 101149 | China | |||
| North Estonian Medical Centre Foundation Center of Pulmonology |
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified 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/
The study consisted of a Pre-treatment, Treatment, and Follow-up Period. The Pre-treatment Period consisted of a screening and baseline visit. This was followed by a 26-week Treatment Period. There was also a Follow-up Period (28 to 32 days) for the collection of Adverse events (AEs).
Participants took part in the study at 14 investigative sites in the Philippines, Latvia, Estonia, South Korea, Peru, China, and Japan from 26 March 2009 to 27 October 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Delamanid 100 mg BID + OBR | Participants received Delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) along with at least 4 additional anti-TB medications per optimized background regimen (OBR) from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on World Health Organization (WHO) guidelines and clinical judgment. |
| FG001 | Delamanid 200 mg BID + OBR | Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population included all participants treated with at least one dose of Delamanid in this study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Delamanid 100 mg BID + OBR | Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. |
| BG001 |
| 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 | Number of Participants With Clinically Significant Abnormality in Vital Signs | Vital signs included weight (kg), body temperature (degree Celsius), heart rate [beats/minute (bpm)], systolic and diastolic blood pressure [millimetre of mercury (mm Hg)]. The criteria for clinically significant abnormal value for: weight was decrease or increase of >=5% in body weight, heart rate was <=60 bpm and decrease of >=15 bpm; >=120 bpm and Increase of >=15 bpm, systolic blood pressure (SBP) <=90 mm Hg and decrease of >=20 mm Hg; diastolic blood pressure (DBP) <=50 mm Hg and decrease of >=15 mm Hg, all vital signs relative to Baseline. Baseline is Study 204 completion visit (Day 84) for participants who complete the baseline visit within 7 days of completing Study 204. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported. | Safety Population included all participants treated with at least one dose of Delamanid in this study. Number analyzed is the number of participants with data available for analyses at the given time point. | Posted | Count of Participants | Participants | From first dose of study drug up to Week 26 |
From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
Safety Population included all participants treated with at least one dose of Delamanid in this study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Delamanid 100 mg BID + OBR | Participants received Delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) along with at least 4 additional anti-TB medications per optimized background regimen (OBR) from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right ventricular failure | Cardiac disorders | MedDra 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Development | Otsuka Pharmaceutical Development & Commercialization, Inc. | 1-609-524-6788 | clinicaltransparency@otsuka-us.com |
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| ID | Term |
|---|---|
| D018088 | Tuberculosis, Multidrug-Resistant |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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| ID | Term |
|---|---|
| C516022 | OPC-67683 |
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|
| OBR | Drug | Selection and administration of the treatment medications (i.e. OBRs) was based on World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study investigators could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results. |
|
| From first dose of study drug up to Week 26 |
| Number of Participants With Abnormality in Audiometry at Baseline | Audiometry assessments were done at Baseline. | Baseline |
| Number of Participants With Abnormality in Visual Acuity | From first dose of study drug up to Week 26 |
| Number of Participants With Abnormality in Neurological and Psychiatric Assessment Reported as Treatment-emergent Adverse Event (TEAE) | Participants with abnormal neurological and psychiatric assessments were reported. An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
| Number of Participants With Clinical Significant Abnormality in Thyroid Function Test Reported as TEAE | Participants with abnormal thyroid free T4 nanograms per deciliter (ng/dL) and thyroid-stimulating hormone (>=3 OR <=0.3 micro-international units per litre (uIU/mL). An AE is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
| Number of Participants With Any Concomitant Medication Usage | Concomitant medications are defined as medications that started on or after the first day of study treatment or were started prior to study treatment but were ongoing on the first day of study treatment. | From first dose of study drug up to Week 26 |
| Percentage of Participants With At Least One TEAEs and Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. An SAE is an AE that resulted in death, inpatient hospitalization/prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
| Number of Participants With Clinical Significant Abnormality in Coagulation (PT and aPTT) Reported as TEAE | Participants with clinically significant abnormal coagulation (prothrombin time (PT) >17.5 seconds and activated partial thromboplastin time (aPTT) >45 seconds) were reported. | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
| Number of Participants With Clinical Significant Abnormality in Cortisol | Participants with clinically significant cortisol >=26 micrograms/decilitre (ug/dL) were reported. | From first dose of study drug up to Week 26 |
| Week 26 |
| Percentage of Treatment Responders Using Solid Culture Medium | Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with SCC at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of MTB at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion) | Week 26 |
| Percentage of Treatment Non-responders Using the MGIT Culture System | Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. The total percentage of treatment non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion) | Week 26 |
| Percentage of Treatment Non-responders Using Solid Culture Medium | Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. Treatment Non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the Solid culture medium (ie, sputum culture conversion). | Week 26 |
| Percentage of Sustained Converters Using the MGIT Culture System | The total percentage of sustained converters was defined as the percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion) | Week 26 |
| Percentage of Sustained Converters Using Solid Culture Medium | The total percentage of sustained converters was defined as percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Determined by Solid culture medium. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion) | Week 26 |
| Percentage of New Converters Using the MGIT Culture System | The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). | Week 26 |
| Percentage of New Converters Using Solid Culture Medium | The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion). | Week 26 |
| Percentage of Non-converters Using the MGIT Culture System | The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). | Week 26 |
| Percentage of Non-converters Using Solid Culture Medium | The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion). | Week 26 |
| Percentage of Reverters Using the MGIT Culture System | The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). | Week 26 |
| Percentage of Reverters Using Solid Culture Medium | The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion). | Week 26 |
| Percentage of Participants Who Developed Resistance to Delamanid While on Treatment | Resistance was defined as mycobacterium tuberculosis (MTB) growth on the delamanid-containing medium of greater than 1% of that on the drug-free medium. The overall resistance to delamanid during the study was assessed. | Up to Week 26 |
| Tallinn |
| 13419 |
| Estonia |
| Tartu University Lung Hospital | Tartu | 51014 | Estonia |
| State Agency of Tuberculosis and Lung Disease | Riga | LV2118 | Latvia |
| Hospital Nacional Sergio E. Bernales | Lima | 41 | Peru |
| Tropical Disease Foundation | Makati City | 1229 | Philippines |
| Younsei University Medical Center | Seoul | 120-752 | South Korea |
| Asan Medical Center | Seoul | 138-736 | South Korea |
| Subject met Withdrawal Criteria |
|
| Subject was Withdrawn from Participation by the Investigator |
|
| Subject withdrew consent to participate |
|
| Protocol Deviation |
|
| Delamanid 200 mg BID + OBR |
Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Delamanid 100 mg BID + OBR | Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. |
| OG001 | Delamanid 200 mg BID + OBR | Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study. |
|
|
| Primary | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values | 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. Only categories with data are reported. | Safety Population included all participants treated with at least one dose of Delamanid in this study. | Posted | Count of Participants | Participants | From first dose of study drug up to Week 26 |
|
|
|
| Primary | Number of Participants With Clinical Significant Abnormality in Laboratory Test | Laboratory assessments included parameters for serum chemistry (alkaline phosphatase, alanine aminotransferase, alanine transaminase, total bilirubin, cholesterol, gamma-glutamyl transferase, glucose, lactic dehydrogenase, potassium, sodium, triglycerides, uric acid), hematology (white blood cell count eosinophils, absolute, hematocrit, hemoglobin, lymphocytes, absolute, mean corpuscular volume, neutrophil, bands, neutrophils, neutrophils, absolute, platelet count, red blood cell (RBC) count, reticulocyte count) and urinalysis (blood, epithelial cast, granular cast, hyaline cast, RBCs per high power field (RBC/HPF)). The participants were categorized based on the clinically significant laboratory values as per predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for laboratory assessments are reported. | Safety Population included all participants treated with at least one dose of Delamanid in this study. Number analyzed is the number of participants with at least one post-baseline result for the given test. | Posted | Count of Participants | Participants | From first dose of study drug up to Week 26 |
|
|
|
| Primary | Number of Participants With Abnormality in Audiometry at Baseline | Audiometry assessments were done at Baseline. | Safety Population included all participants treated with at least one dose of Delamanid in this study. | Posted | Count of Participants | Participants | Baseline |
|
|
|
| Primary | Number of Participants With Abnormality in Visual Acuity | Safety Population included all participants treated with at least one dose of Delamanid in this study. | Posted | Count of Participants | Participants | From first dose of study drug up to Week 26 |
|
|
|
| Primary | Number of Participants With Abnormality in Neurological and Psychiatric Assessment Reported as Treatment-emergent Adverse Event (TEAE) | Participants with abnormal neurological and psychiatric assessments were reported. An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. | Safety Population included all participants treated with at least one dose of Delamanid in this study. | Posted | Count of Participants | Participants | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
|
|
|
| Primary | Number of Participants With Clinical Significant Abnormality in Thyroid Function Test Reported as TEAE | Participants with abnormal thyroid free T4 nanograms per deciliter (ng/dL) and thyroid-stimulating hormone (>=3 OR <=0.3 micro-international units per litre (uIU/mL). An AE is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. | Safety Population included all participants treated with at least one dose of Delamanid in this study. | Posted | Count of Participants | Participants | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
|
|
|
| Primary | Number of Participants With Any Concomitant Medication Usage | Concomitant medications are defined as medications that started on or after the first day of study treatment or were started prior to study treatment but were ongoing on the first day of study treatment. | Safety Population included all participants treated with at least one dose of Delamanid in this study. | Posted | Count of Participants | Participants | From first dose of study drug up to Week 26 |
|
|
|
| Primary | Percentage of Participants With At Least One TEAEs and Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. An SAE is an AE that resulted in death, inpatient hospitalization/prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. | Safety Population included all participants treated with at least one dose of Delamanid in this study. | Posted | Number | percentage of participants | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
|
|
|
| Primary | Number of Participants With Clinical Significant Abnormality in Coagulation (PT and aPTT) Reported as TEAE | Participants with clinically significant abnormal coagulation (prothrombin time (PT) >17.5 seconds and activated partial thromboplastin time (aPTT) >45 seconds) were reported. | Safety Population included all participants treated with at least one dose of Delamanid in this study. Number analyzed is the number of participants with at least one post-baseline result for the given test. | Posted | Count of Participants | Participants | From first dose through 28 days after last dose of study drug (up to approximately 30 weeks) |
|
|
|
| Primary | Number of Participants With Clinical Significant Abnormality in Cortisol | Participants with clinically significant cortisol >=26 micrograms/decilitre (ug/dL) were reported. | Safety Population included all participants treated with at least one dose of Delamanid in this study. Overall number of participants analyzed is the number of participants with at least one post-baseline result for the given test. | Posted | Count of Participants | Participants | From first dose of study drug up to Week 26 |
|
|
|
| Secondary | Percentage of Treatment Responders Using the Mycobacterial Growth Indicator Tube (MGIT) Culture System | Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with sputum culture conversion (SCC) at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis (MTB) at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Treatment Responders Using Solid Culture Medium | Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with SCC at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of MTB at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion) | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Treatment Non-responders Using the MGIT Culture System | Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. The total percentage of treatment non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion) | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Treatment Non-responders Using Solid Culture Medium | Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. Treatment Non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the Solid culture medium (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Sustained Converters Using the MGIT Culture System | The total percentage of sustained converters was defined as the percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion) | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Sustained Converters Using Solid Culture Medium | The total percentage of sustained converters was defined as percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Determined by Solid culture medium. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion) | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
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| Secondary | Percentage of New Converters Using the MGIT Culture System | The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
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| Secondary | Percentage of New Converters Using Solid Culture Medium | The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
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| Secondary | Percentage of Non-converters Using the MGIT Culture System | The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
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| Secondary | Percentage of Non-converters Using Solid Culture Medium | The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
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| Secondary | Percentage of Reverters Using the MGIT Culture System | The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
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| Secondary | Percentage of Reverters Using Solid Culture Medium | The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion). | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 26 |
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| Secondary | Percentage of Participants Who Developed Resistance to Delamanid While on Treatment | Resistance was defined as mycobacterium tuberculosis (MTB) growth on the delamanid-containing medium of greater than 1% of that on the drug-free medium. The overall resistance to delamanid during the study was assessed. | Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint. | Posted | Number | percentage of participants | Up to Week 26 |
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|
| 1 |
| 137 |
| 19 |
| 137 |
| 126 |
| 137 |
| EG001 | Delamanid 200 mg BID + OBR | Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study. | 0 | 76 | 6 | 76 | 73 | 76 |
| Hepatitis acute | Hepatobiliary disorders | MedDra 13.1 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDra 13.1 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDra 13.1 | Systematic Assessment |
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| Lung infection | Infections and infestations | MedDra 13.1 | Systematic Assessment |
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| Pulmonary tuberculoma | Infections and infestations | MedDra 13.1 | Systematic Assessment |
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| Tuberculosis | Infections and infestations | MedDra 13.1 | Systematic Assessment |
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| Gun shot wound | Injury, poisoning and procedural complications | MedDra 13.1 | Systematic Assessment |
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| Intentional overdose | Injury, poisoning and procedural complications | MedDra 13.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDra 13.1 | Systematic Assessment |
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| Electrocardiogram Qt prolonged | Investigations | MedDra 13.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDra 13.1 | Systematic Assessment |
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| Lip and/or oral cavity cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 13.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDra 13.1 | Systematic Assessment |
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| Polyneuropathy | Nervous system disorders | MedDra 13.1 | Systematic Assessment |
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| Abortion incomplete | Pregnancy, puerperium and perinatal conditions | MedDra 13.1 | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDra 13.1 | Systematic Assessment |
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| Suicide attempt | Psychiatric disorders | MedDra 13.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDra 13.1 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDra 13.1 | Systematic Assessment |
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| Hydropneumothorax | Respiratory, thoracic and mediastinal disorders | MedDra 13.1 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDra 13.1 | Systematic Assessment |
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| Transaminases increased | Investigations | MedDra 13.1 | Systematic Assessment |
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| Tinnitus | Ear and labyrinth disorders | MedDRA 13.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
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| Folliculitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Lung infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Tracheobronchitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Blood cortisol increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Alcohol abuse | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 13.1 | 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.
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| QTcB Interval, New Onset (>450 msec) |
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| QTcB Interval, New Onset (>480 msec) |
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| QTcB Interval, New Onset (>500 msec) |
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| QTcB Interval, Increase from Baseline >=30 msec and <=60 msec |
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| QTcB Interval, Increase from Baseline >60 msec |
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| QTcF Interval, New Onset (>450 msec) |
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| QTcF Interval, New Onset (>480 msec) |
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| QTcF Interval, New Onset (>500 msec) |
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| QTcF Interval, Increase from Baseline >=30 msec and <=60 msec |
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| QTcF Interval, Increase from Baseline >60 msec |
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| Ventricular Rate Notable Changes, <50 bpm and Decrease from Baseline of >=25% |
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| Ventricular Rate Notable Changes, >100 bpm and Increase from Baseline of >=25% |
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| New Abnormal U Waves |
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| New ST Segment Changes |
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| New T Waves Changes |
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| New Abnormal Rhythm |
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| New Conduction |
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| Alanine Aminotransferase (SGPT) |
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| Aspartate Aminotransferase (SGOT) |
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| Total Bilirubin |
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| Cholesterol |
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| GAMMA-Glutamyl Transferase |
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| Glucose |
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| Lactic Dehydrogenase |
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| Potassium |
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| Sodium |
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| Triglycerides |
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| Uric Acid |
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| Eosinophils, Absolute |
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| Hematocrit |
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| Hemoglobin |
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| Lymphocytes, Absolute |
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| Mean Corpuscular Volume |
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| Neutrophil, Bands |
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| Neutrophils |
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| Neutrophils, Absolute |
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| Platelet Count |
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| Red Blood Cell Count |
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| Reticulocyte Count |
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| White Blood Count |
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| Blood Urine Present |
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| Epithelial Cast in Urine |
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| Granular Cast in Urine |
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| Hyaline Cast in Urine |
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| RBC/HPF in Urine |
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| Prothrombin Time |
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