Trial Outcomes & Findings for A Trial to Evaluate OPC 67683 in Participants With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB) (NCT NCT00685360)
NCT ID: NCT00685360
Last Updated: 2021-12-01
Results Overview
Sputum culture conversion was defined to occur at the time of the collection of a sputum specimen with mycobacterial culture negative for growth of Mycobacterium tuberculosis (MTB) followed by at least one additional sputum specimen with mycobacterial culture negative for growth at least 27 days after the first negative specimen and not followed by any sputum specimens positive for growth in the MGIT system at any point during the remainder of the 84-day trial after the first negative culture.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
481 participants
Primary outcome timeframe
From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)
Results posted on
2021-12-01
Participant Flow
Participants took part in the study at 17 investigative sites in the Philippines, Latvia, Estonia, South Korea, Peru, China, Japan, Egypt, and the United States from 08 May 2008 to 11 June 2010.
Participants with pulmonary sputum culture-positive, multidrug-resistant tuberculosis were randomized in 1:1:1 ratio to 1 of the 3 groups to receive either optimized background regimen (OBR) + 100 milligrams (mg) BID delamanid or OBR + 200 mg BID delamanid or OBR + placebo.
Participant milestones
| Measure |
Delamanid 100 mg BID + OBR
Participants received delamanid 100 mg (two 50 mg tablets), orally, twice daily (BID) with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on World Health Organization (WHO) guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Overall Study
STARTED
|
161
|
160
|
160
|
|
Overall Study
Modified Intent-to-Treat (MITT)
|
141
|
136
|
125
|
|
Overall Study
MITT (Solid Culture)
|
119
|
115
|
113
|
|
Overall Study
COMPLETED
|
143
|
146
|
145
|
|
Overall Study
NOT COMPLETED
|
18
|
14
|
15
|
Reasons for withdrawal
| Measure |
Delamanid 100 mg BID + OBR
Participants received delamanid 100 mg (two 50 mg tablets), orally, twice daily (BID) with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on World Health Organization (WHO) guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
2
|
|
Overall Study
Adverse Event
|
4
|
6
|
4
|
|
Overall Study
Subject Met (Protocol Specified) Withdrawal Criteria
|
1
|
0
|
2
|
|
Overall Study
Subject was Withdrawn From Participation by the Investigator
|
0
|
4
|
1
|
|
Overall Study
Subject Withdrew Consent to Participate
|
13
|
2
|
5
|
|
Overall Study
Protocol Deviation
|
0
|
1
|
1
|
Baseline Characteristics
A Trial to Evaluate OPC 67683 in Participants With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB)
Baseline characteristics by cohort
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Total
n=481 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
37.4 years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
35.4 years
STANDARD_DEVIATION 12.0 • n=7 Participants
|
36.1 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
36.3 years
STANDARD_DEVIATION 11.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
157 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
105 Participants
n=5 Participants
|
108 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
324 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
42 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
133 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
118 Participants
n=5 Participants
|
116 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
347 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
38 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
95 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
82 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
257 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
41 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
128 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)Population: Modified Intent-to-Treat (MITT) Population included all participants who had sputum cultures positive for multidrug resistant tuberculosis (MDR TB) at baseline (Day -1 and/or Day 1) using the MGIT system.
Sputum culture conversion was defined to occur at the time of the collection of a sputum specimen with mycobacterial culture negative for growth of Mycobacterium tuberculosis (MTB) followed by at least one additional sputum specimen with mycobacterial culture negative for growth at least 27 days after the first negative specimen and not followed by any sputum specimens positive for growth in the MGIT system at any point during the remainder of the 84-day trial after the first negative culture.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=141 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=136 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=125 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using the Mycobacteria Growth Indicator Tube (MGIT) System
|
45.4 percentage of participants
|
41.9 percentage of participants
|
29.6 percentage of participants
|
PRIMARY outcome
Timeframe: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.
Time to maximum (peak) plasma concentration following the first daily dose (Cmax1) was reported as tmax1 and time to maximum (peak) plasma concentration following the second daily dose (Cmax2) was reported as tmax2. Data for Tmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 1: tmax1
|
4.00 hours
Interval 1.85 to 10.0
|
4.00 hours
Interval 2.0 to 10.0
|
—
|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 1: tmax2
|
14.0 hours
Interval 11.7 to 24.0
|
14.0 hours
Interval 11.9 to 24.0
|
—
|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 14: tmax1
|
3.02 hours
Interval 0.0 to 10.0
|
3.00 hours
Interval 0.0 to 10.0
|
—
|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 14: tmax2
|
14.0 hours
Interval 11.9 to 24.0
|
14.0 hours
Interval 12.0 to 24.0
|
—
|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 28: tmax1
|
3.02 hours
Interval 0.0 to 10.0
|
3.00 hours
Interval 0.0 to 10.0
|
—
|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 28: tmax2
|
14.0 hours
Interval 12.0 to 24.0
|
14.0 hours
Interval 12.0 to 24.0
|
—
|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 56: tmax1
|
3.02 hours
Interval 0.0 to 9.97
|
3.02 hours
Interval 0.0 to 10.0
|
—
|
|
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose
Day 56: tmax2
|
14.0 hours
Interval 12.0 to 24.0
|
14.0 hours
Interval 12.0 to 24.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.
Maximum (peak) plasma concentration following the first daily dose was reported as Cmax1 and maximum (peak) plasma concentration following the second daily dose was reported as Cmax2. Data for Cmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 1: Cmax1
|
135 nanograms (ng)/mL
Standard Deviation 54.9
|
187 nanograms (ng)/mL
Standard Deviation 74.3
|
—
|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 1: Cmax2
|
151 nanograms (ng)/mL
Standard Deviation 60.4
|
228 nanograms (ng)/mL
Standard Deviation 91.5
|
—
|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 14: Cmax1
|
369 nanograms (ng)/mL
Standard Deviation 137
|
547 nanograms (ng)/mL
Standard Deviation 200
|
—
|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 14: Cmax2
|
361 nanograms (ng)/mL
Standard Deviation 127
|
513 nanograms (ng)/mL
Standard Deviation 178
|
—
|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 28: Cmax1
|
404 nanograms (ng)/mL
Standard Deviation 144
|
599 nanograms (ng)/mL
Standard Deviation 222
|
—
|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 28: Cmax2
|
381 nanograms (ng)/mL
Standard Deviation 128
|
560 nanograms (ng)/mL
Standard Deviation 196
|
—
|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 56: Cmax1
|
414 nanograms (ng)/mL
Standard Deviation 165
|
611 nanograms (ng)/mL
Standard Deviation 217
|
—
|
|
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose
Day 56: Cmax2
|
400 nanograms (ng)/mL
Standard Deviation 162
|
588 nanograms (ng)/mL
Standard Deviation 213
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.
Data for AUC0-24h up to Day 56 was collected on Days 1, 14, 28 and 56.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid
Day 1: AUC0-24h
|
2441 hours*nanograms (h*ng)/mL
Standard Deviation 880
|
3598 hours*nanograms (h*ng)/mL
Standard Deviation 1312
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid
Day 14: AUC0-24h
|
7234 hours*nanograms (h*ng)/mL
Standard Deviation 2346
|
10490 hours*nanograms (h*ng)/mL
Standard Deviation 3377
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid
Day 28: AUC0-24h
|
7700 hours*nanograms (h*ng)/mL
Standard Deviation 2322
|
11251 hours*nanograms (h*ng)/mL
Standard Deviation 3626
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid
Day 56: AUC0-24h
|
7925 hours*nanograms (h*ng)/mL
Standard Deviation 2973
|
11837 hours*nanograms (h*ng)/mL
Standard Deviation 3975
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.
Data for Rac (Cmax) up to Day 56 was collected on Days 14, 28 and 56. Rac (Cmax) on Days 14, 28 or 56 compared to Cmax on Day 1 was computed.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid
Day 14: Rac Cmax1
|
3.05 ratio
Standard Deviation 1.28
|
4.74 ratio
Standard Deviation 19.5
|
—
|
|
Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid
Day 14: Rac Cmax2
|
2.65 ratio
Standard Deviation 1.11
|
2.43 ratio
Standard Deviation 0.870
|
—
|
|
Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid
Day 28: Rac Cmax1
|
3.35 ratio
Standard Deviation 1.63
|
4.94 ratio
Standard Deviation 18.0
|
—
|
|
Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid
Day 28: Rac Cmax2
|
2.85 ratio
Standard Deviation 1.65
|
2.65 ratio
Standard Deviation 1.01
|
—
|
|
Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid
Day 56: Rac Cmax1
|
3.37 ratio
Standard Deviation 1.46
|
5.09 ratio
Standard Deviation 18.0
|
—
|
|
Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid
Day 56: Rac Cmax2
|
2.92 ratio
Standard Deviation 1.43
|
2.81 ratio
Standard Deviation 1.19
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.
Data for Rac (AUC) up to Day 56 was collected on Days 14, 28 and 56. Rac (AUC) on Days 14, 28 or 56 compared to AUC0-24h on Day 1 was computed.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid
Day 14: Rac AUC0-24h
|
3.14 ratio
Standard Deviation 0.965
|
3.13 ratio
Standard Deviation 1.06
|
—
|
|
Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid
Day 28: Rac AUC0-24h
|
3.35 ratio
Standard Deviation 1.24
|
3.33 ratio
Standard Deviation 1.12
|
—
|
|
Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid
Day 56: Rac AUC0-24h
|
3.41 ratio
Standard Deviation 1.19
|
3.52 ratio
Standard Deviation 1.38
|
—
|
PRIMARY outcome
Timeframe: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point for the specified category.
Data for Tmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: Tmax at Day 56
|
4.00 hours
Interval 0.0 to 24.0
|
4.00 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
All Metabolites: Tmax at Day 1
|
NA hours
Data is not available as the concentration of metabolites was below the level of detection on Day 1.
|
NA hours
Data is not available as the concentration of metabolites was below the level of detection on Day 1.
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: Tmax at Day 14
|
13.0 hours
Interval 0.0 to 24.0
|
13.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: Tmax at Day 28
|
3.97 hours
Interval 0.0 to 24.0
|
3.99 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: Tmax at Day 56
|
3.97 hours
Interval 0.0 to 24.0
|
4.00 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: Tmax at Day 14
|
12.0 hours
Interval 0.0 to 24.0
|
9.97 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: Tmax at Day 28
|
9.97 hours
Interval 0.0 to 24.0
|
9.97 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: Tmax at Day 56
|
9.97 hours
Interval 0.0 to 24.0
|
12.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: Tmax at Day 14
|
14.0 hours
Interval 0.0 to 24.0
|
12.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: Tmax at Day 28
|
3.01 hours
Interval 0.0 to 24.0
|
4.00 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: Tmax at Day 56
|
3.03 hours
Interval 0.0 to 24.0
|
4.00 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: Tmax at Day 14
|
24.0 hours
Interval 0.0 to 24.0
|
24.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: Tmax at Day 28
|
9.99 hours
Interval 0.0 to 24.0
|
13.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: Tmax at Day 56
|
9.97 hours
Interval 0.0 to 24.0
|
9.99 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: Tmax at Day 14
|
24.0 hours
Interval 0.0 to 24.0
|
24.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: Tmax at Day 28
|
10.0 hours
Interval 0.0 to 24.0
|
12.9 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: Tmax at Day 56
|
9.96 hours
Interval 0.0 to 24.0
|
9.97 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: Tmax at Day 14
|
11.0 hours
Interval 0.0 to 24.0
|
10.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: Tmax at Day 28
|
9.97 hours
Interval 0.0 to 24.0
|
9.97 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: Tmax at Day 56
|
9.97 hours
Interval 0.0 to 24.0
|
9.97 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: Tmax at Day 14
|
13.0 hours
Interval 0.0 to 24.0
|
10.0 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: Tmax at Day 28
|
4.02 hours
Interval 0.0 to 24.0
|
4.00 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: Tmax at Day 56
|
4.02 hours
Interval 0.0 to 24.0
|
9.97 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: Tmax at Day 14
|
13.0 hours
Interval 0.0 to 24.0
|
9.98 hours
Interval 0.0 to 24.0
|
—
|
|
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: Tmax at Day 28
|
3.00 hours
Interval 0.0 to 24.0
|
4.00 hours
Interval 0.0 to 24.0
|
—
|
PRIMARY outcome
Timeframe: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point for the specified category.
Data for Cmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
All Metabolites: Cmax at Day 1
|
NA ng/mL
Standard Deviation NA
Data is not available as the concentration of metabolites was below the level of detection on Day 1.
|
NA ng/mL
Standard Deviation NA
Data is not available as the concentration of metabolites was below the level of detection on Day 1.
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: Cmax at Day 14
|
40.9 ng/mL
Standard Deviation 29.9
|
57.1 ng/mL
Standard Deviation 40.7
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: Cmax at Day 28
|
48.9 ng/mL
Standard Deviation 31.4
|
78.3 ng/mL
Standard Deviation 53.0
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: Cmax at Day 56
|
60.6 ng/mL
Standard Deviation 37.7
|
90.3 ng/mL
Standard Deviation 58.5
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: Cmax at Day 14
|
78.3 ng/mL
Standard Deviation 35.1
|
124 ng/mL
Standard Deviation 57.8
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: Cmax at Day 28
|
121 ng/mL
Standard Deviation 57.4
|
187 ng/mL
Standard Deviation 78.5
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: Cmax at Day 56
|
151 ng/mL
Standard Deviation 67.3
|
233 ng/mL
Standard Deviation 94.5
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: Cmax at Day 14
|
32.5 ng/mL
Standard Deviation 15.9
|
46.5 ng/mL
Standard Deviation 24.2
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: Cmax at Day 28
|
47.1 ng/mL
Standard Deviation 22.1
|
69.9 ng/mL
Standard Deviation 32.0
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: Cmax at Day 56
|
59.2 ng/mL
Standard Deviation 30.5
|
84.3 ng/mL
Standard Deviation 41.5
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: Cmax at Day 14
|
5.44 ng/mL
Standard Deviation 4.04
|
7.61 ng/mL
Standard Deviation 4.51
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: Cmax at Day 28
|
16.9 ng/mL
Standard Deviation 11.7
|
25.5 ng/mL
Standard Deviation 17.0
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: Cmax at Day 56
|
34.7 ng/mL
Standard Deviation 20.5
|
53.4 ng/mL
Standard Deviation 30.3
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: Cmax at Day 14
|
26.6 ng/mL
Standard Deviation 20.2
|
32.6 ng/mL
Standard Deviation 17.1
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: Cmax at Day 28
|
66.5 ng/mL
Standard Deviation 34.9
|
84.9 ng/mL
Standard Deviation 34.5
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: Cmax at Day 56
|
107 ng/mL
Standard Deviation 46.6
|
138 ng/mL
Standard Deviation 47.9
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: Cmax at Day 14
|
19.5 ng/mL
Standard Deviation 11.7
|
26.5 ng/mL
Standard Deviation 11.6
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: Cmax at Day 28
|
39.4 ng/mL
Standard Deviation 17.1
|
53.6 ng/mL
Standard Deviation 18.7
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: Cmax at Day 56
|
57.4 ng/mL
Standard Deviation 22.6
|
79.3 ng/mL
Standard Deviation 26.3
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: Cmax at Day 14
|
3.19 ng/mL
Standard Deviation 2.26
|
4.38 ng/mL
Standard Deviation 3.35
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: Cmax at Day 28
|
4.95 ng/mL
Standard Deviation 4.37
|
7.74 ng/mL
Standard Deviation 6.37
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: Cmax at Day 56
|
6.38 ng/mL
Standard Deviation 5.65
|
9.92 ng/mL
Standard Deviation 7.04
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: Cmax at Day 14
|
23.1 ng/mL
Standard Deviation 22.1
|
33.4 ng/mL
Standard Deviation 27.3
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: Cmax at Day 28
|
31.2 ng/mL
Standard Deviation 31.8
|
48.5 ng/mL
Standard Deviation 41.3
|
—
|
|
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: Cmax at Day 56
|
33.3 ng/mL
Standard Deviation 23.0
|
56.1 ng/mL
Standard Deviation 39.7
|
—
|
PRIMARY outcome
Timeframe: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point for the specified category.
Data for AUC0-24h up to Day 56 was collected on Days 1, 14, 28 and 56.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: AUC0-24h at Day 14
|
482 h*ng/mL
Standard Deviation 475
|
707 h*ng/mL
Standard Deviation 589
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: AUC0-24h at Day 28
|
655 h*ng/mL
Standard Deviation 695
|
1013 h*ng/mL
Standard Deviation 883
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6722: AUC0-24h at Day 56
|
699 h*ng/mL
Standard Deviation 489
|
1191 h*ng/mL
Standard Deviation 862
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
All Metabolites: AUC0-24h at Day 1
|
NA h*ng/mL
Standard Deviation NA
Data is not available as the concentration of metabolites was below the level of detection on Day 1.
|
NA h*ng/mL
Standard Deviation NA
Data is not available as the concentration of metabolites was below the level of detection on Day 1.
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: AUC0-24h at Day 14
|
848 h*ng/mL
Standard Deviation 647
|
1192 h*ng/mL
Standard Deviation 859
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: AUC0-24h at Day 28
|
1022 h*ng/mL
Standard Deviation 679
|
1610 h*ng/mL
Standard Deviation 1097
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6704: AUC0-24h at Day 56
|
1251 h*ng/mL
Standard Deviation 766
|
1902 h*ng/mL
Standard Deviation 1252
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: AUC0-24h at Day 14
|
1597 h*ng/mL
Standard Deviation 632
|
2485 h*ng/mL
Standard Deviation 920
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: AUC0-24h at Day 28
|
2480 h*ng/mL
Standard Deviation 1051
|
3857 h*ng/mL
Standard Deviation 1486
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6705: AUC0-24h at Day 56
|
3125 h*ng/mL
Standard Deviation 1397
|
4907 h*ng/mL
Standard Deviation 1987
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: AUC0-24h at Day 14
|
685 h*ng/mL
Standard Deviation 339
|
992 h*ng/mL
Standard Deviation 525
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: AUC0-24h at Day 28
|
1004 h*ng/mL
Standard Deviation 474
|
1475 h*ng/mL
Standard Deviation 676
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6706: AUC0-24h at Day 56
|
1256 h*ng/mL
Standard Deviation 643
|
1796 h*ng/mL
Standard Deviation 870
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: AUC0-24h at Day 14
|
108 h*ng/mL
Standard Deviation 81.9
|
153 h*ng/mL
Standard Deviation 93.2
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: AUC0-24h at Day 28
|
349 h*ng/mL
Standard Deviation 240
|
524 h*ng/mL
Standard Deviation 342
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6717: AUC0-24h at Day 56
|
720 h*ng/mL
Standard Deviation 436
|
1112 h*ng/mL
Standard Deviation 623
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: AUC0-24h at Day 14
|
528 h*ng/mL
Standard Deviation 360
|
687 h*ng/mL
Standard Deviation 363
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: AUC0-24h at Day 28
|
1424 h*ng/mL
Standard Deviation 757
|
1800 h*ng/mL
Standard Deviation 726
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6718: AUC0-24h at Day 56
|
2285 h*ng/mL
Standard Deviation 992
|
2954 h*ng/mL
Standard Deviation 994
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: AUC0-24h at Day 14
|
396 h*ng/mL
Standard Deviation 193
|
551 h*ng/mL
Standard Deviation 222
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: AUC0-24h at Day 28
|
822 h*ng/mL
Standard Deviation 353
|
1120 h*ng/mL
Standard Deviation 368
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6720: AUC0-24h at Day 56
|
1206 h*ng/mL
Standard Deviation 474
|
1668 h*ng/mL
Standard Deviation 549
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: AUC0-24h at Day 14
|
65.4 h*ng/mL
Standard Deviation 49.7
|
90.5 h*ng/mL
Standard Deviation 68.7
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: AUC0-24h at Day 28
|
103 h*ng/mL
Standard Deviation 92.9
|
161 h*ng/mL
Standard Deviation 134
|
—
|
|
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
DM-6721: AUC0-24h at Day 56
|
132 h*ng/mL
Standard Deviation 118
|
210 h*ng/mL
Standard Deviation 154
|
—
|
PRIMARY outcome
Timeframe: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: Due to limited measurable data as the metabolite concentration was below the level of detection on Day 1 for delamanid metabolites, PK analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (Cmax) was not available.
Data for Rac (Cmax) up to Day 56 was to be collected on Days 1, 14, 28 and 56. Rac (Cmax) on Days 14, 28 or 56 compared to Cmax on Day 1 was to be computed. Due to limited measurable data on Day 1 for delamanid metabolites, pharmacokinetic (PK) analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (Cmax) was not available.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56Population: Due to limited measurable data as the metabolite concentration was below the level of detection on Day 1 for delamanid metabolites, PK analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (AUC) was not available.
Data for Rac (AUC) up to Day 56 was to be collected on Days 1, 14, 28 and 56. Rac (AUC) on Days 14, 28 or 56 compared to AUC0-24h on Day 1 was to be computed. Due to limited measurable data on Day 1 for delamanid metabolites, PK analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (AUC) was not available.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose on Day 56Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis for the specified category.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6704
|
195 hours
Standard Deviation 115
|
191 hours
Standard Deviation 67.2
|
—
|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6705
|
231 hours
Standard Deviation 84.7
|
233 hours
Standard Deviation 87.9
|
—
|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6706
|
180 hours
Standard Deviation 43.1
|
184 hours
Standard Deviation 40.3
|
—
|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6717
|
265 hours
Standard Deviation 98.2
|
265 hours
Standard Deviation 115
|
—
|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6718
|
302 hours
Standard Deviation 132
|
305 hours
Standard Deviation 131
|
—
|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6720
|
394 hours
Standard Deviation 158
|
424 hours
Standard Deviation 192
|
—
|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6721
|
168 hours
Standard Deviation 49.7
|
153 hours
Standard Deviation 53.1
|
—
|
|
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722
t1/2 for DM-6722
|
134 hours
Standard Deviation 85.1
|
148 hours
Standard Deviation 60.3
|
—
|
SECONDARY outcome
Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.
A participant achieving SCC using solid culture media was defined as one with sputum culture negative for growth of MTB on Day 57, and (a) not followed by a positive culture at any point thereafter, and (b) confirmed by at least one additional negative sputum culture at Day 84.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=119 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=115 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=113 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using Solid Culture Media
|
53.8 percentage of participants
|
65.2 percentage of participants
|
33.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Day 84Population: Last Observation Carried Forward(LOCF)Population:all randomized participants with positive sputum culture for MDR TB at baseline(pre-dose)by MGIT system and when sputum collection was not possible,a specimen was contaminated with other bacteria,or a result was missing due to a participant withdrawing from trial, the preceding non-missing result for that variable at a postbaseline visit was carried forward. Overall number analyzed=participants with data available for analysis.
Mean change from baseline in time to culture positivity using the MGIT system was the value for "time to results" when a sputum culture result was positive (in days) using the MGIT system during the routine 42-day incubation period. A longer time to culture positivity represented a lower burden of MTB organisms present in the sputum. Baseline was defined as the average of Day -1 and Day 1 values, if the cultures on both days were positive; if only one culture was positive, the value for the positive culture was used as baseline.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=140 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=135 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=123 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Change From Baseline in Time to Culture Positivity Using the MGIT System
|
25.9 days
Standard Error 1.0
|
26.0 days
Standard Error 1.0
|
24.2 days
Standard Error 1.1
|
SECONDARY outcome
Timeframe: Baseline to Day 57Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system. Overall number analyzed are the participants with data available for analysis.
AUC of change from baseline for time to culture positivity (i.e., TTD) (Days 0 to 57), summarizes overall participant response for treatment period. Larger AUC of change from baseline for time to culture positivity would strongly suggest a clinical response with reduction of burden of MTB organisms in sputum. For this analysis, ti=visit day of each visit; t0=Day 0, t1=Day 8, t2=Day 15, etc. and xi=change from baseline in time to culture positivity at each visit; AUC at each visit was determined as AUCi=(ti - ti-1)(xi+ xi-1)/2. Average AUC of change from baseline was the sum of all AUCi divided by a given participant's duration in the trial up to 57 days. Baseline (Day 0)=the average of Day -1 and Day 1 values, if cultures on both days were positive; if only one culture was positive, value for time to culture positivity for positive culture was used as baseline.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=137 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=134 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=121 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Area Under the Curve (AUC) of Change From Baseline in Time to Culture Positivity in the MGIT System
|
13.4 days
Standard Error 0.7
|
13.1 days
Standard Error 0.7
|
11.1 days
Standard Error 0.7
|
SECONDARY outcome
Timeframe: Day 57Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=141 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=136 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=125 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Sputum Culture Negative at Day 57 Using the MGIT System Without Consideration of Subsequent Culture Results
|
56.0 percentage of participants
|
52.9 percentage of participants
|
44.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 57 and Day 84Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=141 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=136 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=125 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using the MGIT System Without Respect to Interim Culture Results
|
50.4 percentage of participants
|
44.9 percentage of participants
|
40.8 percentage of participants
|
SECONDARY outcome
Timeframe: Day 57Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=119 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=115 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=113 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Sputum Culture Negative at Day 57 Using Solid Culture Media Without Respect to Subsequent Culture Results
|
65.5 percentage of participants
|
71.3 percentage of participants
|
49.6 percentage of participants
|
SECONDARY outcome
Timeframe: Day 57 and Day 84Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=119 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=115 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=113 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using Solid Culture Media Without Respect to Interim Culture Results
|
60.5 percentage of participants
|
67.8 percentage of participants
|
45.1 percentage of participants
|
SECONDARY outcome
Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)Population: MITT Population included all participants who had sputum cultures positive for multidrug resistant tuberculosis (MDR TB) at baseline (Day -1 and/or Day 1) using the MGIT system.
A participant achieving SCC using solid media is defined as one with sputum culture negative for growth of MTB on Day 57, and (a) not followed by a positive culture at any point thereafter, and (b) confirmed by at least one additional negative sputum culture at Day 84. A dose response in the percentage of participants achieving SCC using the MGIT system was tested by the Cochran-Armitage linear trend test with equally spaced dose scores (0, 1, and 2 for placebo, 100 mg BID, and 200 mg BID, respectively).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=141 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=136 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=125 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved SCC From the MGIT System Analyzed by Cochran-Armitage Linear Trend Test for Dose-response Relationship
|
45.4 percentage of participants
|
41.9 percentage of participants
|
29.6 percentage of participants
|
SECONDARY outcome
Timeframe: Day 57Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.
Initial SCC occurred at the time of the collection of the first sputum specimen with mycobacterial culture negative for growth of MTB using the MGIT system followed by at least one additional MGIT negative sputum specimen at least 27 days after the first negative specimen and no sputum specimens MGIT positive for growth at any point between the negative MGIT sputum specimens. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=141 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=136 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=125 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Initial SCC Using the MGIT System
|
50.4 percentage of participants
|
50.0 percentage of participants
|
31.2 percentage of participants
|
SECONDARY outcome
Timeframe: Day 57Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.
Initial SCC occurred at the time of the collection of the first sputum specimen with mycobacterial culture negative for growth of MTB using solid culture media that was followed by at least one additional negative sputum specimen at least 27 days after the first negative specimen and no sputum specimens positive for growth on solid culture media at any point between the negative sputum specimens using solid culture media. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=119 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=115 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=113 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Initial SCC Using the Solid Culture Media
|
60.5 percentage of participants
|
68.7 percentage of participants
|
37.2 percentage of participants
|
SECONDARY outcome
Timeframe: Day 57Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.
Final SCC was defined as SCC at Day 57 or the latest time point of the first negative sputum culture establishing SCC for a given participant after the last positive sputum culture observed during the 56-day treatment period, whichever comes first. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=141 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=136 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=125 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Final SCC Using MGIT
|
45.4 percentage of participants
|
41.9 percentage of participants
|
29.6 percentage of participants
|
SECONDARY outcome
Timeframe: Day 57Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.
Final SCC is defined as SCC at Day 57 or the latest time point of the first negative sputum culture establishing SCC for a given participant after the last positive sputum culture observed during the 56-day treatment period, whichever comes first. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=119 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=115 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=113 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Final SCC Using Solid Culture Media
|
53.8 percentage of participants
|
65.2 percentage of participants
|
33.6 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose of study drug up to post treatment period (Day 84)Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Clinically Significant Physical Examination Findings, Including Vision and Neuropsychiatric Assessments
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose of study drug up to post treatment period (Day 84)Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation. Number analyzed is the number of participants who had at least one post-baseline numerical result for the given test.
Criteria for potentially clinically significant vital sign abnormalities: Heart rate \[beats per minute (BPM)\]: \>=120, increase \>=15, \<=60, decrease \>=15; systolic blood pressure \[millimeter of mercury (mmHg)\]: \>=160, increase \>=20, \<=90, decrease \>=20; diastolic blood pressure (mmHg): \>=105, increase \>=15, \<=50, decrease \>=15; weight (kg) gain: increase \>=5%; or weight loss: decrease \>=5%; temperature \[degrees Celsius (C)\]: \>=38.5, increase of \>=1.1. Only categories with at least 1 participant with event are reported.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Weight: Decrease of >=5% in Body Weight
|
16.4 percentage of participants
|
13.9 percentage of participants
|
6.4 percentage of participants
|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Weight: Increase of >=5% in Body Weight
|
35.2 percentage of participants
|
32.3 percentage of participants
|
44.6 percentage of participants
|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Temperature: >=38.5C + Increase of >=1.1C
|
0.0 percentage of participants
|
0.6 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Heart Rate: <=60 BPM + Decrease of >=15
|
4.4 percentage of participants
|
5.1 percentage of participants
|
2.5 percentage of participants
|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Heart Rate: >=120 BPM + Increase of >=15
|
0.6 percentage of participants
|
0.6 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Systolic Blood Pressure: <=90 mmHg + Decrease of >=20 mmHg
|
4.4 percentage of participants
|
9.5 percentage of participants
|
8.9 percentage of participants
|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Systolic Blood Pressure: >=160 mmHg + Increase of >=20 mmHg
|
0.6 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Clinically Significant Vital Sign Abnormalities
Diastolic Blood Pressure <=50 mmHg + Decrease of >=15 mmHg
|
1.9 percentage of participants
|
0.0 percentage of participants
|
0.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Criteria for categorical changes in 6 12-lead Electrocardiogram results: Vent Rate Outliers Notable Decreases- \>= 25% decrease from Baseline and ventricular rate \< 50 beats per minute (beats/min), notable increases- \>= 25% decrease from Baseline and ventricular rate \> 100 beats/min; PR outliers notable changes- \>= 25% change from Baseline when PR \> 200 milliseconds (msec); QRS outliers notable changes- \>= 25% change from Baseline when QRS \> 100 msec; QT new onset (\> 500 msec); QT correction with Bazett formula (QTcB) and QT interval with Fridericia's correction (QTcF) new onset \> 500 msec, \> 480 msec, \> 450 msec, where new onset (\> 450, 480, 500 msec) means a participant who attains a value \> 450, 480, 500 msec during Treatment Period but not at each Baseline Visit; change \>= 30, \<= 60 msec; change \> 60 msec; and new abnormal U waves, ST segment changes, T wave changes, abnormal rhythm, RBBB, LBBB, myocardial infarction(MI). Only categories with at least 1 participant with event are r
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcB Change >= 30, <= 60 msec
|
36.6 percentage of participants
|
44.3 percentage of participants
|
17.5 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
Vent Rate Outliers Notable Decreases
|
0.0 percentage of participants
|
1.2 percentage of participants
|
0.6 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
Vent Rate Outliers Notable Increases
|
1.2 percentage of participants
|
2.5 percentage of participants
|
3.7 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QT New Onset (> 500 msec)
|
0.0 percentage of participants
|
1.8 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcB New Onset (> 500 msec)
|
1.2 percentage of participants
|
1.2 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcB New Onset (> 480 msec)
|
7.4 percentage of participants
|
8.1 percentage of participants
|
3.1 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcB New Onset (> 450 msec)
|
39.1 percentage of participants
|
37.5 percentage of participants
|
19.3 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcB Change >60 msec
|
1.2 percentage of participants
|
3.1 percentage of participants
|
0.6 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcF New Onset (> 480 msec)
|
0.0 percentage of participants
|
3.1 percentage of participants
|
0.6 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcF New Onset (> 450 msec)
|
15.5 percentage of participants
|
13.7 percentage of participants
|
6.2 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcF Change >= 30, <= 60 msec
|
36.0 percentage of participants
|
44.3 percentage of participants
|
15.6 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
QTcF Change > 60 msec
|
3.1 percentage of participants
|
3.7 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
New Abnormal Rhythm
|
9.3 percentage of participants
|
10.6 percentage of participants
|
17.5 percentage of participants
|
|
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56
New Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)
|
2.4 percentage of participants
|
3.7 percentage of participants
|
7.5 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose of study drug up to post treatment period (Day 84)Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation. Number analyzed is the number of participants with at least one non-missing result for a given lab test.
The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant laboratory values in clinical chemistry, hematology, coagulation, adrenal function tests, urinalysis and thyroid function tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance. The categories with at least one participant with abnormal lab value as assessed by the investigator are reported.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Sodium (mEq/L) <132, >148
|
17.4 percentage of participants
|
16.3 percentage of participants
|
17.5 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Creatinine (mg/dL) >2.0
|
1.2 percentage of participants
|
0.6 percentage of participants
|
1.9 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Glucose (mg/dL) <50, >300
|
1.9 percentage of participants
|
1.9 percentage of participants
|
4.4 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Potassium (mEq/L) <3, >5.5
|
16.1 percentage of participants
|
18.1 percentage of participants
|
18.1 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Triglycerides (mg/dL) >300
|
4.3 percentage of participants
|
3.8 percentage of participants
|
4.4 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Urea Nitrogen (mg/dL) >34
|
1.9 percentage of participants
|
1.3 percentage of participants
|
1.9 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Mean Corpuscular Volume (femtoliter [fL]) <=78, >=105
|
30.4 percentage of participants
|
26.3 percentage of participants
|
26.9 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Neutrophil, Bands (%) >=8.0
|
2.6 percentage of participants
|
2.6 percentage of participants
|
1.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Platelet Count (thous/µL) <100, >600
|
16.1 percentage of participants
|
15.6 percentage of participants
|
13.8 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Reticulocyte Count (%) <=.1, >=3
|
21.1 percentage of participants
|
21.3 percentage of participants
|
23.8 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Blood (Urinalysis): Positive
|
55.8 percentage of participants
|
58.6 percentage of participants
|
55.4 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
RBC Casts
|
—
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Neutrophils, Absolute (thous/µL) <=2.0
|
13.7 percentage of participants
|
10.0 percentage of participants
|
13.8 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
White Blood Count Casts
|
100.0 percentage of participants
|
100.0 percentage of participants
|
—
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Eosinophils, Absolute (thousands per microliter [thous/µL]) >=0.8
|
14.9 percentage of participants
|
18.1 percentage of participants
|
24.4 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Hematocrit (%); Male <32, >58, Female <27, >58
|
15.5 percentage of participants
|
11.3 percentage of participants
|
11.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Hemoglobin (g/dL) <10, >16
|
28.6 percentage of participants
|
23.1 percentage of participants
|
22.5 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Lymphocytes, Absolute (thous/µL) >=5.0
|
0.6 percentage of participants
|
—
|
1.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Mean Corpuscular Hemoglobin (picograms [pg]) >40.0
|
0.6 percentage of participants
|
—
|
—
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Mean Corpuscular Hemoglobin Concentrate (g/dL) >40.0
|
—
|
—
|
0.6 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Granular Cast
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Hyaline Cast
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
White Blood Count (thous/µL) <3, >=15
|
11.2 percentage of participants
|
12.5 percentage of participants
|
13.8 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Epithelial Casts
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Albumin (grams per deciliter [g/dL]) <2.6
|
8.1 percentage of participants
|
3.1 percentage of participants
|
8.8 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Alanine Transaminase (ALT) (units per liter [U/L]) >150.0
|
0.6 percentage of participants
|
0.6 percentage of participants
|
1.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Aspartate aminotransferase (AST) (U/L) >150.0
|
1.2 percentage of participants
|
1.9 percentage of participants
|
2.5 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Bilirubin, Total (mg/dL) >2
|
—
|
0.6 percentage of participants
|
—
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Calcium (mg/dL) <7, >11.5
|
0.6 percentage of participants
|
1.9 percentage of participants
|
3.8 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Chloride (milliequivalents per liter [mEq/L]) <85
|
0.6 percentage of participants
|
2.5 percentage of participants
|
0.6 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Cholesterol (mg/dL) >300.0
|
0.6 percentage of participants
|
0.6 percentage of participants
|
—
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Gamma-glutamyl Transferase (U/L); Male >225.0, Female >175.0
|
3.1 percentage of participants
|
—
|
1.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Lactic Dehydrogenase (U/L) >400
|
1.2 percentage of participants
|
3.8 percentage of participants
|
1.9 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Protein, Total Serum (g/dL) >9.5
|
0.6 percentage of participants
|
—
|
—
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Uric Acid (mg/dL) >12
|
24.2 percentage of participants
|
27.9 percentage of participants
|
22.9 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Activated Partial Thromboplastin Time (seconds [sec]) >45.0
|
14.9 percentage of participants
|
12.5 percentage of participants
|
16.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Cortisol, Serum (micrograms per deciliter [µg/dL]) >=26
|
36.0 percentage of participants
|
48.8 percentage of participants
|
29.4 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Free Thyroxine (T4) [nanograms per deciliter (ng/dL)] <=.30, >=2.5
|
1.9 percentage of participants
|
0.6 percentage of participants
|
1.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Thyroid Stimulating Hormone (micro-international units per milliliter [µIU/mL]) <=.30 >=3
|
23.6 percentage of participants
|
20.0 percentage of participants
|
26.3 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Prothrombin Time (sec) >17.5
|
4.7 percentage of participants
|
3.7 percentage of participants
|
1.4 percentage of participants
|
|
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities
Red Blood Cell (RBC) Count (million per microliter [mill/µL]) <4, >=6.5
|
31.7 percentage of participants
|
23.1 percentage of participants
|
26.3 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose of study drug up to post treatment period (Day 84)Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Clinically Significant Audiometry Findings
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose of study drug up to post treatment period (Day 84)Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
The concomitant anti-TB medication were classified as per WHO 2008 guidelines and included: Category 1- first-line oral anti-tuberculosis drugs; Category 2- injectable anti-tuberculosis drugs; Category 3- fluoroquinolones; Category 4- oral bacteriostatic second-line anti-tuberculosis drugs; Category 5- anti-tuberculosis drugs with unclear efficacy or unclear role in MDR-TB treatment (not recommended by WHO for routine use in MDR-TB participants).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants Using Concomitant Medications
Concomitant Medications (Excluding Anti-TB Medications)
|
98.8 percentage of participants
|
98.8 percentage of participants
|
98.8 percentage of participants
|
|
Percentage of Participants Using Concomitant Medications
Concomitant Anti-TB Medications: Category 4
|
99.4 percentage of participants
|
98.8 percentage of participants
|
99.4 percentage of participants
|
|
Percentage of Participants Using Concomitant Medications
Concomitant Anti-TB Medications: Category 1
|
90.7 percentage of participants
|
90.6 percentage of participants
|
88.8 percentage of participants
|
|
Percentage of Participants Using Concomitant Medications
Concomitant Anti-TB Medications: Category 2
|
88.2 percentage of participants
|
80.0 percentage of participants
|
88.8 percentage of participants
|
|
Percentage of Participants Using Concomitant Medications
Concomitant Anti-TB Medications: Category 3
|
97.5 percentage of participants
|
98.8 percentage of participants
|
98.1 percentage of participants
|
|
Percentage of Participants Using Concomitant Medications
Concomitant Anti-TB Medications: Category 5
|
26.1 percentage of participants
|
27.5 percentage of participants
|
27.5 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose of study drug up to post treatment period (Day 84)Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including e.g., an abnormal laboratory assessment result), symptom or disease temporally associated with participation in the clinical trial, whether or not it is considered causally related to the medicinal product or procedures of the clinical trial. A clinically significant worsening in the health of the participant compared with the participant's health status documented at baseline constituted a TEAE.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)
|
90.1 percentage of participants
|
93.1 percentage of participants
|
93.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, and 2, 3, 4, 10, 12, and 24 hours post dose on Day 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Time-matched Change From Baseline (Day -1) in QTcF at Day 56
Day 56: 24 Hours Post Dose
|
15.5 msec
Standard Deviation 18.9
|
18.3 msec
Standard Deviation 18.5
|
3.4 msec
Standard Deviation 15.0
|
|
Time-matched Change From Baseline (Day -1) in QTcF at Day 56
Day 56: 2 Hours Post Dose
|
11.8 msec
Standard Deviation 16.3
|
14.6 msec
Standard Deviation 18.8
|
-0.5 msec
Standard Deviation 14.3
|
|
Time-matched Change From Baseline (Day -1) in QTcF at Day 56
Day 56: 3 Hours Post Dose
|
12.8 msec
Standard Deviation 16.6
|
14.7 msec
Standard Deviation 16.0
|
-0.4 msec
Standard Deviation 14.5
|
|
Time-matched Change From Baseline (Day -1) in QTcF at Day 56
Day 56: 4 Hours Post Dose
|
16.8 msec
Standard Deviation 16.3
|
19.4 msec
Standard Deviation 17.3
|
5.0 msec
Standard Deviation 15.8
|
|
Time-matched Change From Baseline (Day -1) in QTcF at Day 56
Day 56: 10 Hours Post Dose
|
16.5 msec
Standard Deviation 17.4
|
20.8 msec
Standard Deviation 17.3
|
5.2 msec
Standard Deviation 15.5
|
|
Time-matched Change From Baseline (Day -1) in QTcF at Day 56
Day 56: 12 Hours Post Dose
|
15.6 msec
Standard Deviation 17.4
|
16.7 msec
Standard Deviation 17.0
|
2.6 msec
Standard Deviation 15.6
|
SECONDARY outcome
Timeframe: Baseline, Days 1, 14, 28 and 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Mean Change From Baseline in QTcF
Day 1
|
0.1 msec
Standard Deviation 7.1
|
0.0 msec
Standard Deviation 7.1
|
-1.8 msec
Standard Deviation 8.3
|
|
Mean Change From Baseline in QTcF
Day 14
|
7.7 msec
Standard Deviation 11.1
|
9.3 msec
Standard Deviation 11.2
|
0.8 msec
Standard Deviation 11.0
|
|
Mean Change From Baseline in QTcF
Day 28
|
9.9 msec
Standard Deviation 12.3
|
14.1 msec
Standard Deviation 13.2
|
2.4 msec
Standard Deviation 11.2
|
|
Mean Change From Baseline in QTcF
Day 56
|
14.9 msec
Standard Deviation 14.3
|
17.5 msec
Standard Deviation 13.9
|
2.7 msec
Standard Deviation 12.2
|
SECONDARY outcome
Timeframe: Baseline, Days 1, 14, 28 and 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Mean Change From Baseline in QTcB
Day 14
|
6.5 msec
Standard Deviation 11.5
|
8.1 msec
Standard Deviation 10.7
|
0.5 msec
Standard Deviation 12.0
|
|
Mean Change From Baseline in QTcB
Day 1
|
0.8 msec
Standard Deviation 7.4
|
1.5 msec
Standard Deviation 7.2
|
-0.4 msec
Standard Deviation 8.5
|
|
Mean Change From Baseline in QTcB
Day 28
|
7.9 msec
Standard Deviation 12.1
|
12.5 msec
Standard Deviation 14.0
|
2.1 msec
Standard Deviation 13.0
|
|
Mean Change From Baseline in QTcB
Day 56
|
11.7 msec
Standard Deviation 14.5
|
14.6 msec
Standard Deviation 12.6
|
2.3 msec
Standard Deviation 13.6
|
SECONDARY outcome
Timeframe: Baseline, Days 1, 14, 28 and 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Mean Change From Baseline in Ventricular Rate
Day 1
|
0.9 beats/min
Standard Deviation 5.5
|
2.0 beats/min
Standard Deviation 4.9
|
1.9 beats/min
Standard Deviation 5.3
|
|
Mean Change From Baseline in Ventricular Rate
Day 14
|
-1.9 beats/min
Standard Deviation 8.1
|
-2.1 beats/min
Standard Deviation 9.0
|
-0.6 beats/min
Standard Deviation 8.6
|
|
Mean Change From Baseline in Ventricular Rate
Day 28
|
-3.2 beats/min
Standard Deviation 8.6
|
-3.2 beats/min
Standard Deviation 9.3
|
-0.8 beats/min
Standard Deviation 10.2
|
|
Mean Change From Baseline in Ventricular Rate
Day 56
|
-4.8 beats/min
Standard Deviation 10.3
|
-4.7 beats/min
Standard Deviation 12.6
|
-1.2 beats/min
Standard Deviation 10.6
|
SECONDARY outcome
Timeframe: Baseline, Days 1, 14, 28 and 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Mean Change From Baseline in PR Interval
Day 1
|
-1.3 msec
Standard Deviation 5.6
|
-1.0 msec
Standard Deviation 4.8
|
-1.6 msec
Standard Deviation 5.4
|
|
Mean Change From Baseline in PR Interval
Day 14
|
-0.7 msec
Standard Deviation 7.7
|
-0.8 msec
Standard Deviation 7.2
|
-1.4 msec
Standard Deviation 8.1
|
|
Mean Change From Baseline in PR Interval
Day 28
|
-1.4 msec
Standard Deviation 8.1
|
-0.8 msec
Standard Deviation 8.4
|
-0.6 msec
Standard Deviation 7.4
|
|
Mean Change From Baseline in PR Interval
Day 56
|
-1.6 msec
Standard Deviation 8.3
|
0.3 msec
Standard Deviation 8.1
|
-0.5 msec
Standard Deviation 7.2
|
SECONDARY outcome
Timeframe: Baseline, Days 1, 14, 28 and 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Mean Change From Baseline in QRS Interval
Day 1
|
-0.3 msec
Standard Deviation 2.8
|
-0.5 msec
Standard Deviation 2.8
|
-0.2 msec
Standard Deviation 3.3
|
|
Mean Change From Baseline in QRS Interval
Day 14
|
0.1 msec
Standard Deviation 3.3
|
0.1 msec
Standard Deviation 3.5
|
-0.1 msec
Standard Deviation 3.9
|
|
Mean Change From Baseline in QRS Interval
Day 28
|
0.4 msec
Standard Deviation 3.6
|
-0.1 msec
Standard Deviation 4.2
|
-0.3 msec
Standard Deviation 3.8
|
|
Mean Change From Baseline in QRS Interval
Day 56
|
0.7 msec
Standard Deviation 4.1
|
-0.2 msec
Standard Deviation 4.0
|
0.2 msec
Standard Deviation 3.8
|
SECONDARY outcome
Timeframe: Baseline, Days 1, 14, 28 and 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Mean Change From Baseline in QT Interval
Day 1
|
-1.0 msec
Standard Deviation 11.5
|
-2.7 msec
Standard Deviation 10.9
|
-4.3 msec
Standard Deviation 11.6
|
|
Mean Change From Baseline in QT Interval
Day 14
|
9.5 msec
Standard Deviation 18.2
|
11.1 msec
Standard Deviation 20.1
|
1.1 msec
Standard Deviation 18.5
|
|
Mean Change From Baseline in QT Interval
Day 28
|
13.4 msec
Standard Deviation 20.3
|
16.3 msec
Standard Deviation 21.1
|
2.5 msec
Standard Deviation 20.2
|
|
Mean Change From Baseline in QT Interval
Day 56
|
20.1 msec
Standard Deviation 23.5
|
22.0 msec
Standard Deviation 28.4
|
3.1 msec
Standard Deviation 21.7
|
SECONDARY outcome
Timeframe: Baseline, Days 1, 14, 28 and 56Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).
Any changes in the ECG waves or segments as assessed by the investigator were reported.
Outcome measures
| Measure |
Delamanid 100 mg BID + OBR
n=161 Participants
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 Participants
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 Participants
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 1: New Abnormal U Waves
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 1: New ST Segment Changes
|
1.8 percentage of participants
|
0.6 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 1: New T Wave Changes
|
9.9 percentage of participants
|
6.2 percentage of participants
|
6.2 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 14: New Abnormal U Waves
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 14: New ST Segment Changes
|
3.1 percentage of participants
|
0.6 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 14: New T Wave Changes
|
12.4 percentage of participants
|
5.6 percentage of participants
|
4.3 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 28: New Abnormal U Waves
|
1.2 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 28: New ST Segment Changes
|
1.8 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 28: New T Wave Changes
|
11.8 percentage of participants
|
5.0 percentage of participants
|
10.0 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 56: New Abnormal U Waves
|
1.2 percentage of participants
|
0.6 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 56: New ST Segment Changes
|
2.4 percentage of participants
|
0.6 percentage of participants
|
1.8 percentage of participants
|
|
Percentage of Participants With Change in ECG Morphological Patterns From Baseline
Day 56: New T Wave Changes
|
11.1 percentage of participants
|
10.6 percentage of participants
|
5.0 percentage of participants
|
Adverse Events
Delamanid 100 mg BID + OBR
Serious events: 16 serious events
Other events: 145 other events
Deaths: 0 deaths
Delamanid 200 mg BID + OBR
Serious events: 20 serious events
Other events: 148 other events
Deaths: 1 deaths
Placebo + OBR
Serious events: 14 serious events
Other events: 147 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Delamanid 100 mg BID + OBR
n=161 participants at risk
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 participants at risk
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 participants at risk
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.9%
3/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.2%
2/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Hydropneumothorax
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Blood and lymphatic system disorders
Anaemia
|
1.9%
3/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.2%
2/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Ear and labyrinth disorders
Deafness
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
General disorders
Chest discomfort
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Hepatobiliary disorders
Hepatitis
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Hepatobiliary disorders
Liver disorder
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Infections and infestations
Oropharyngeal candidiasis
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Injury, poisoning and procedural complications
Fall
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Investigations
Electrocardiogram QT prolonged
|
4.3%
7/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.6%
9/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.9%
3/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Investigations
Electrocardiogram T wave abnormal
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.2%
2/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Syncope
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Agitation
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Delusional disorder, persecutory type
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Hallucination, auditory
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Ideas of reference
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Mental disorder
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Psychotic disorder
|
1.2%
2/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.2%
2/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.9%
3/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Schizophrenia, paranoid type
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.62%
1/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Vascular disorders
Haematoma
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Vascular disorders
Hypotension
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
Other adverse events
| Measure |
Delamanid 100 mg BID + OBR
n=161 participants at risk
Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Delamanid 200 mg BID + OBR
n=160 participants at risk
Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
Placebo + OBR
n=160 participants at risk
Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).
Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.3%
15/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.8%
14/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Blood and lymphatic system disorders
Eosinophilia
|
4.3%
7/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
9.4%
15/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Blood and lymphatic system disorders
Reticulocytosis
|
11.8%
19/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
12.5%
20/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.6%
17/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Cardiac disorders
Palpitations
|
8.1%
13/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
12.5%
20/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.2%
10/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Ear and labyrinth disorders
Tinnitus
|
9.9%
16/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
13.8%
22/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
7.5%
12/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Eye disorders
Vision blurred
|
7.5%
12/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
9.4%
15/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.6%
9/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
4.3%
7/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
3.1%
5/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Abdominal distension
|
3.1%
5/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.6%
9/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
3.1%
5/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Abdominal pain
|
9.9%
16/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
7.5%
12/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
2.5%
4/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
4.4%
7/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
25.5%
41/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
22.5%
36/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
23.8%
38/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Constipation
|
3.7%
6/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.4%
20/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
7.5%
12/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
13.8%
22/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Dyspepsia
|
3.7%
6/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.8%
14/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
3.8%
6/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Gastritis
|
5.0%
8/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.8%
14/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.0%
16/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Nausea
|
36.0%
58/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
40.6%
65/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
33.1%
53/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Toothache
|
3.7%
6/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
4.4%
7/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Gastrointestinal disorders
Vomiting
|
29.8%
48/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
36.2%
58/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
27.5%
44/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
General disorders
Asthenia
|
12.4%
20/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
16.9%
27/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
12.5%
20/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
General disorders
Chest pain
|
9.9%
16/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.1%
13/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
4.4%
7/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
General disorders
Injection site pain
|
8.1%
13/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
7.5%
12/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
14.4%
23/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
General disorders
Malaise
|
7.5%
12/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.0%
16/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
7.5%
12/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
General disorders
Pyrexia
|
5.6%
9/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
11.2%
18/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
11.2%
18/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Investigations
Electrocardiogram QT prolonged
|
6.8%
11/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.1%
13/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.9%
3/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Metabolism and nutrition disorders
Anorexia
|
14.3%
23/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
21.2%
34/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
15.0%
24/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
19.3%
31/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
23.8%
38/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
21.9%
35/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
12.4%
20/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
18.1%
29/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
15.0%
24/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.9%
32/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
26.9%
43/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
28.7%
46/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.5%
12/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.0%
16/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
11.9%
19/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.2%
10/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.3%
15/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
13.1%
21/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
16.2%
26/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.62%
1/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.6%
9/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.7%
6/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Dizziness
|
29.8%
48/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
30.6%
49/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
30.6%
49/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Dysgeusia
|
3.1%
5/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.2%
10/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.2%
10/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Headache
|
22.4%
36/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
25.6%
41/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
18.8%
30/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Hypoaesthesia
|
7.5%
12/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
4.4%
7/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Paraesthesia
|
10.6%
17/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
12.5%
20/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
7.5%
12/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Somnolence
|
6.8%
11/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.6%
9/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
9.4%
15/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Nervous system disorders
Tremor
|
11.8%
19/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.0%
16/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.1%
13/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Anxiety
|
5.6%
9/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
3.1%
5/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Depression
|
2.5%
4/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.1%
13/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
3.1%
5/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Psychiatric disorders
Insomnia
|
26.1%
42/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
31.9%
51/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
26.2%
42/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
8/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
4.4%
7/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.9%
3/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
3.1%
5/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
9.9%
16/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
8.8%
14/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.0%
16/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
3.1%
5/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.6%
9/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
3.8%
6/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
7.5%
12/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.0%
16/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
3.1%
5/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
0.00%
0/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.6%
9/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
10.6%
17/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
5.0%
8/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.3%
15/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
9.4%
15/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
12.5%
20/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.0%
8/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
1.9%
3/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.2%
10/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
6.2%
10/161 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
7.5%
12/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
6.9%
11/160 • From first dose of study drug up to post treatment period (up to Day 84)
ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 1-609-524-6788
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER