Back to resultsA Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683
Primary Purpose
Tuberculosis, Multidrug-Resistant
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Delamanid
OBR
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis, Multidrug-Resistant
Eligibility Criteria
Inclusion Criteria:
- Provide written, informed consent prior to all trial-related procedures
- Male or female participants aged between 18 and 64 years, inclusive, at the time of enrollment into the 242-07-204 trial. Participants who were 64 years at the time of 204 enrollment and who are now 65 years, are eligible for this trial.
- Participants who have completed trial 242-07-204
- Participants judged by the investigator to have the potential for clinical benefit from OPC-67683 exposure
- Able to produce sputum for mycobacterial culture or able to obtain sputum produced through induction
- Female participants of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control throughout the participation in the trial and for 22 weeks after last dose.
- Male participants must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30 weeks after last dose.
Exclusion Criteria:
- Greater than 30 days has elapsed from the participant's date of completion in the 242-07-204 trial or greater than 30 days has elapsed since the patient's trial investigator's site was initiated in this trial, whichever is later.
- A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time.
- Use of the medications in Section 5.4.7 including: use of amiodarone at any time during the previous 12 months, use of other anti-arrhythmics for the previous 30 days, and use of certain other medications, including certain anti-depressants, anti-histamines, and macrolides, for the previous 14 days.
- Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels ≥265 moles per liter (mol/L) or hepatic impairment characterized by Alanine aminotransferase (ALT) and/or aspartate transferase (AST) levels 3 times the upper limit of the laboratory reference range from the screening lab results.
- Current clinically relevant changes in the electrocardiogram (ECG) (between Trial 242-07-204 Day 56 assessment and baseline) such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 milliseconds (msec) (in both male and female participants), or the corrected QT interval using Fridericia's method (QTcF) interval over 450 msec in male participants and 470 msec in female participants.
- Current clinically relevant cardiovascular disorders such as heart failure, coronary artery disease, uncontrolled or poorly controlled hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction.
- Any participants with known or reported significant psychiatric history.
- For participants with human immunodeficiency virus (HIV) infection, CD4 cell count less than 350/cubic millimeter (mm^3) or on treatment with antiretroviral medication for HIV infection.
- Karnofsky score under 50 percent (%) while hospitalized and less than 60% while not hospitalized.
- Any current diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated.
- Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
- Known or suspected alcohol abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the participants in the opinion of the investigator.
- Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 other than OPC-67683 given as IMP in trial 242-07-204.
- Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form.
- Recent use of methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, tetrahydrocannabinol, barbiturates, and opiates as determined by a urine drug screen, unless evidence is provided that the positive drug screen is the result of authorized medications or products prescribed by a physician for a non-abuse related indication.
- Any disorder that in the judgment of the investigator makes the participant not a good candidate for the trial or may prevent the participant from reliably participating in the entire course of the trial.
Sites / Locations
- Beijing Chest Hospital
- North Estonian Medical Centre Foundation Center of Pulmonology
- Tartu University Lung Hospital
- Younsei University Medical Center
- Asan Medical Center
- State Agency of Tuberculosis and Lung Disease
- Hospital Nacional Sergio E. Bernales
- Tropical Disease Foundation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Delamanid 100 mg BID + OBR
Delamanid 200 mg BID + OBR
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
Number of Participants With Abnormality in Audiometry at Baseline
Audiometry assessments were done at Baseline.
Number of Participants With Abnormality in Visual Acuity
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.
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.
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.
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.
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.
Number of Participants With Clinical Significant Abnormality in Cortisol
Participants with clinically significant cortisol >=26 micrograms/decilitre (ug/dL) were reported.
Secondary Outcome Measures
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).
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)
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)
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).
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)
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)
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).
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).
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).
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).
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).
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).
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.
Full Information
NCT ID
NCT02573350
First Posted
September 29, 2015
Last Updated
September 30, 2021
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02573350
Brief Title
A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683
Official Title
A Phase 2, Multi-center, Uncontrolled, Open-label Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683 as 100 mg BID With Optional Titration to 200 mg BID for up to Six Months Exposure in Patients With Pulmonary Multi-drug Resistant Tuberculosis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
March 26, 2009 (Actual)
Primary Completion Date
October 27, 2011 (Actual)
Study Completion Date
October 27, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Multidrug-Resistant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
213 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Delamanid 100 mg BID + OBR
Arm Type
Experimental
Arm Description
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.
Arm Title
Delamanid 200 mg BID + OBR
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Delamanid
Other Intervention Name(s)
OPC-67683, Deltyba
Intervention Description
Delamanid was administered orally twice daily as 50-mg tablets under fed conditions in the morning and evening.
Intervention Type
Drug
Intervention Name(s)
OBR
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Clinically Significant Abnormality in Vital Signs
Description
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.
Time Frame
From first dose of study drug up to Week 26
Title
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values
Description
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.
Time Frame
From first dose of study drug up to Week 26
Title
Number of Participants With Clinical Significant Abnormality in Laboratory Test
Description
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.
Time Frame
From first dose of study drug up to Week 26
Title
Number of Participants With Abnormality in Audiometry at Baseline
Description
Audiometry assessments were done at Baseline.
Time Frame
Baseline
Title
Number of Participants With Abnormality in Visual Acuity
Time Frame
From first dose of study drug up to Week 26
Title
Number of Participants With Abnormality in Neurological and Psychiatric Assessment Reported as Treatment-emergent Adverse Event (TEAE)
Description
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.
Time Frame
From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
Title
Number of Participants With Clinical Significant Abnormality in Thyroid Function Test Reported as TEAE
Description
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.
Time Frame
From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
Title
Number of Participants With Any Concomitant Medication Usage
Description
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.
Time Frame
From first dose of study drug up to Week 26
Title
Percentage of Participants With At Least One TEAEs and Serious Adverse Events (SAEs)
Description
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.
Time Frame
From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
Title
Number of Participants With Clinical Significant Abnormality in Coagulation (PT and aPTT) Reported as TEAE
Description
Participants with clinically significant abnormal coagulation (prothrombin time (PT) >17.5 seconds and activated partial thromboplastin time (aPTT) >45 seconds) were reported.
Time Frame
From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
Title
Number of Participants With Clinical Significant Abnormality in Cortisol
Description
Participants with clinically significant cortisol >=26 micrograms/decilitre (ug/dL) were reported.
Time Frame
From first dose of study drug up to Week 26
Secondary Outcome Measure Information:
Title
Percentage of Treatment Responders Using the Mycobacterial Growth Indicator Tube (MGIT) Culture System
Description
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).
Time Frame
Week 26
Title
Percentage of Treatment Responders Using Solid Culture Medium
Description
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)
Time Frame
Week 26
Title
Percentage of Treatment Non-responders Using the MGIT Culture System
Description
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)
Time Frame
Week 26
Title
Percentage of Treatment Non-responders Using Solid Culture Medium
Description
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).
Time Frame
Week 26
Title
Percentage of Sustained Converters Using the MGIT Culture System
Description
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)
Time Frame
Week 26
Title
Percentage of Sustained Converters Using Solid Culture Medium
Description
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)
Time Frame
Week 26
Title
Percentage of New Converters Using the MGIT Culture System
Description
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).
Time Frame
Week 26
Title
Percentage of New Converters Using Solid Culture Medium
Description
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).
Time Frame
Week 26
Title
Percentage of Non-converters Using the MGIT Culture System
Description
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).
Time Frame
Week 26
Title
Percentage of Non-converters Using Solid Culture Medium
Description
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).
Time Frame
Week 26
Title
Percentage of Reverters Using the MGIT Culture System
Description
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).
Time Frame
Week 26
Title
Percentage of Reverters Using Solid Culture Medium
Description
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).
Time Frame
Week 26
Title
Percentage of Participants Who Developed Resistance to Delamanid While on Treatment
Description
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.
Time Frame
Up to Week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provide written, informed consent prior to all trial-related procedures
Male or female participants aged between 18 and 64 years, inclusive, at the time of enrollment into the 242-07-204 trial. Participants who were 64 years at the time of 204 enrollment and who are now 65 years, are eligible for this trial.
Participants who have completed trial 242-07-204
Participants judged by the investigator to have the potential for clinical benefit from OPC-67683 exposure
Able to produce sputum for mycobacterial culture or able to obtain sputum produced through induction
Female participants of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control throughout the participation in the trial and for 22 weeks after last dose.
Male participants must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30 weeks after last dose.
Exclusion Criteria:
Greater than 30 days has elapsed from the participant's date of completion in the 242-07-204 trial or greater than 30 days has elapsed since the patient's trial investigator's site was initiated in this trial, whichever is later.
A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time.
Use of the medications in Section 5.4.7 including: use of amiodarone at any time during the previous 12 months, use of other anti-arrhythmics for the previous 30 days, and use of certain other medications, including certain anti-depressants, anti-histamines, and macrolides, for the previous 14 days.
Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels ≥265 moles per liter (mol/L) or hepatic impairment characterized by Alanine aminotransferase (ALT) and/or aspartate transferase (AST) levels 3 times the upper limit of the laboratory reference range from the screening lab results.
Current clinically relevant changes in the electrocardiogram (ECG) (between Trial 242-07-204 Day 56 assessment and baseline) such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 milliseconds (msec) (in both male and female participants), or the corrected QT interval using Fridericia's method (QTcF) interval over 450 msec in male participants and 470 msec in female participants.
Current clinically relevant cardiovascular disorders such as heart failure, coronary artery disease, uncontrolled or poorly controlled hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction.
Any participants with known or reported significant psychiatric history.
For participants with human immunodeficiency virus (HIV) infection, CD4 cell count less than 350/cubic millimeter (mm^3) or on treatment with antiretroviral medication for HIV infection.
Karnofsky score under 50 percent (%) while hospitalized and less than 60% while not hospitalized.
Any current diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated.
Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
Known or suspected alcohol abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the participants in the opinion of the investigator.
Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 other than OPC-67683 given as IMP in trial 242-07-204.
Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form.
Recent use of methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, tetrahydrocannabinol, barbiturates, and opiates as determined by a urine drug screen, unless evidence is provided that the positive drug screen is the result of authorized medications or products prescribed by a physician for a non-abuse related indication.
Any disorder that in the judgment of the investigator makes the participant not a good candidate for the trial or may prevent the participant from reliably participating in the entire course of the trial.
Facility Information:
Facility Name
Beijing Chest Hospital
City
Beijing
ZIP/Postal Code
101149
Country
China
Facility Name
North Estonian Medical Centre Foundation Center of Pulmonology
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Facility Name
Tartu University Lung Hospital
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Younsei University Medical Center
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
State Agency of Tuberculosis and Lung Disease
City
Riga
ZIP/Postal Code
LV2118
Country
Latvia
Facility Name
Hospital Nacional Sergio E. Bernales
City
Lima
ZIP/Postal Code
41
Country
Peru
Facility Name
Tropical Disease Foundation
City
Makati City
ZIP/Postal Code
1229
Country
Philippines
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
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.
IPD Sharing Access Criteria
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
IPD Sharing URL
https://clinical-trials.otsuka.com
Learn more about this trial
A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683
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