A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683

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.

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.

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.

Audiometry assessments were done at Baseline.

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.

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.

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.

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.

Participants with clinically significant abnormal coagulation (prothrombin time (PT) >17.5 seconds and activated partial thromboplastin time (aPTT) >45 seconds) were reported.

Participants with clinically significant cortisol >=26 micrograms/decilitre (ug/dL) were reported.

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).

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)

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)

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).

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)

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)

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).

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).

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).

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).

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).

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).

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.