Trial Outcomes & Findings for Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy (NCT NCT02367014)
NCT ID: NCT02367014
Last Updated: 2019-12-27
Results Overview
Change in distance walked as measured by meters on the 6-minute walk test from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Assessed at Baseline, Day 5 (end-of-treatment visit)
Results posted on
2019-12-27
Participant Flow
Study Centers: Akron Children's Hospital; Massachusetts General Hospital; University of Pittsburgh School of Medicine; University of California, San Diego
Participant milestones
| Measure |
Low Dose
MTP-131: MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
MTP-131: MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
MTP-131: MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
Placebo: Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
9
|
9
|
|
Overall Study
COMPLETED
|
9
|
9
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy
Baseline characteristics by cohort
| Measure |
Low Dose
n=9 Participants
MTP-131: MTP-131 (low dose) administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131: MTP-131 (intermediate dose) administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131: MTP-131 (high dose) administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo: Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
40.8 years
STANDARD_DEVIATION 11.32 • n=5 Participants
|
45.0 years
STANDARD_DEVIATION 14.09 • n=7 Participants
|
42.3 years
STANDARD_DEVIATION 16.84 • n=5 Participants
|
41.9 years
STANDARD_DEVIATION 15.83 • n=4 Participants
|
42.5 years
STANDARD_DEVIATION 14.12 • n=21 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Assessed at Baseline, Day 5 (end-of-treatment visit)Change in distance walked as measured by meters on the 6-minute walk test from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT)
|
13.5 meters
Interval -72.0 to 86.0
|
36.5 meters
Interval -20.0 to 107.0
|
64.5 meters
Interval 4.0 to 133.0
|
20.4 meters
Interval -37.0 to 90.0
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: All participants for whom maximum oxygen uptake was measured at baseline and Day 5
Change in maximum oxygen uptake as measured by mL/kg/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Maximum Oxygen Uptake (ml/kg/Min)
|
0.35 ml/kg/min
Standard Deviation 2.617
|
2.36 ml/kg/min
Standard Deviation 2.714
|
0.64 ml/kg/min
Standard Deviation 3.121
|
2.14 ml/kg/min
Standard Deviation 3.137
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: All participants for whom VE/VCO2 slope measurements were recorded at Baseline and Day 5
Change in ventilatory efficiency as measured by the VE/VCO2 slope from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Ventilatory Efficiency (VE/VCO2 Slope)
|
0.749 VE/VCO2 slope
Standard Deviation 2.9412
|
-0.671 VE/VCO2 slope
Standard Deviation 5.4024
|
-1.681 VE/VCO2 slope
Standard Deviation 3.2834
|
-1.375 VE/VCO2 slope
Standard Deviation 5.5801
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: All participants for whom aerobic efficiency measurements were recorded at Baseline and Day 5
Change in aerobic efficiency as measured by ΔO2 consumption/Δ work ratio from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=7 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Aerobic Efficiency (ΔO2 Consumption/Δ Work Ratio)
|
-0.234 ΔO2 consumption/Δwork ratio
Standard Deviation 4.3414
|
0.643 ΔO2 consumption/Δwork ratio
Standard Deviation 2.7507
|
-0.214 ΔO2 consumption/Δwork ratio
Standard Deviation 1.9727
|
0.738 ΔO2 consumption/Δwork ratio
Standard Deviation 3.5959
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: All participants for whom oxygen utilization measurements were recorded at Baseline and Day 5
Change in oxygen utilization as measured by ΔVO2/ΔlogVE ratio from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=7 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Oxygen Utilization (ΔVO2/ΔlogVE Ratio)
|
-118.87 ΔVO2/ΔlogVE ratio
Standard Deviation 229.105
|
184.99 ΔVO2/ΔlogVE ratio
Standard Deviation 410.093
|
90.13 ΔVO2/ΔlogVE ratio
Standard Deviation 116.281
|
166.50 ΔVO2/ΔlogVE ratio
Standard Deviation 479.145
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom oxygen uptake kinetics was measured
Change in oxygen uptake kinetics (mean response time) as measured by seconds from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=7 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Oxygen Uptake Kinetics (Mean Response Time as Measured by Seconds)
|
6.40 seconds
Standard Deviation 11.402
|
-2.49 seconds
Standard Deviation 26.830
|
-9.75 seconds
Standard Deviation 26.288
|
-7.47 seconds
Standard Deviation 14.357
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom pre-exercise lactate levels were measured
Change in pre-exercise lactate levels as measured by mg/dL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=6 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Pre-exercise Lactate Levels (mg/dL)
|
3.4 mg/dL
Standard Deviation 9.00
|
13.8 mg/dL
Standard Deviation 18.30
|
0.4 mg/dL
Standard Deviation 10.25
|
4.4 mg/dL
Standard Deviation 14.06
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom post- exercise lactate levels were measured
Change in post-exercise lactate levels as measured by mg/dL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=6 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=7 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Post-exercise Lactate Levels (mg/dL)
|
6.9 mg/dL
Standard Deviation 11.87
|
10.6 mg/dL
Standard Deviation 42.93
|
4.3 mg/dL
Standard Deviation 22.10
|
8.4 mg/dL
Standard Deviation 13.21
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak respiratory exchange ratio was measured.
Change in peak respiratory exchange ratio as measured by VCO2/VO2 from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Respiratory Exchange Ratio (VCO2/VO2)
|
0.109 VCO2/VO2 ratio
Standard Deviation 0.0741
|
0.114 VCO2/VO2 ratio
Standard Deviation 0.1803
|
0.010 VCO2/VO2 ratio
Standard Deviation 0.0561
|
0.133 VCO2/VO2 ratio
Standard Deviation 0.1297
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak respiratory rate was measured
Change in peak respiratory rate as measured by breaths/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=6 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=5 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Respiratory Rate (Breaths/Min)
|
1.4 breaths/min
Standard Deviation 6.54
|
-0.7 breaths/min
Standard Deviation 5.72
|
0.9 breaths/min
Standard Deviation 6.24
|
8.2 breaths/min
Standard Deviation 5.26
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak ventilation was measured.
Change in peak ventilation as measured by L/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=6 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Ventilation (L/Min)
|
2.70 L/min
Standard Deviation 8.692
|
8.87 L/min
Standard Deviation 7.975
|
2.49 L/min
Standard Deviation 8.303
|
8.47 L/min
Standard Deviation 8.564
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak heart rate was measured
Change in peak heart rate as measured by beats per minute from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=8 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Heart Rate (Beats/Min)
|
10.1 beats/min
Standard Deviation 11.15
|
16.7 beats/min
Standard Deviation 13.02
|
4.5 beats/min
Standard Deviation 9.58
|
3.8 beats/min
Standard Deviation 7.85
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak oxygen saturation was measured.
Change in peak oxygen saturation as measured by percentage of O2-saturated hemoglobin from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=7 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Oxygen Saturation (% O2-saturated Hemoglobin)
|
0.0 percentage of O2-saturated hemoglobin
Standard Deviation 1.69
|
0.1 percentage of O2-saturated hemoglobin
Standard Deviation 1.07
|
0.6 percentage of O2-saturated hemoglobin
Standard Deviation 0.74
|
0.3 percentage of O2-saturated hemoglobin
Standard Deviation 1.60
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak systolic blood pressure was measured.
Change in peak systolic blood pressure as measured by mmHg from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=7 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=6 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=6 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=7 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Systolic Blood Pressure (mmHg)
|
16.7 mmHg
Standard Deviation 21.00
|
-1.5 mmHg
Standard Deviation 36.47
|
16.0 mmHg
Standard Deviation 12.71
|
-2.7 mmHg
Standard Deviation 21.84
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak diastolic blood pressure was measured
Change in peak diastolic blood pressure as measured by mmHg from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=7 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=5 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=6 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=7 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Diastolic Blood Pressure (mmHg)
|
0.6 mmHg
Standard Deviation 12.67
|
-1.4 mmHg
Standard Deviation 11.13
|
-2.5 mmHg
Standard Deviation 9.07
|
-6.6 mmHg
Standard Deviation 12.74
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom peak Borg dyspnea was measured.
Change in peak Borg dyspnea as measured by 0-10 with 0 meaning no breathlessness and 10 meaning maximal breathlessness from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=7 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Peak Borg Dyspnea
|
-2.00 Units on a scale
Standard Deviation 2.00
|
-2.2 Units on a scale
Standard Deviation 2.23
|
-1.4 Units on a scale
Standard Deviation 1.30
|
-0.4 Units on a scale
Standard Deviation 1.70
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom VO2 was measured.
Change in VO2 anaerobic threshold as measured by mL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=5 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=7 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=4 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in VO2 Anaerobic Threshold (mL)
|
30.00 mL
Standard Deviation 83.93
|
10.8 mL
Standard Deviation 80.35
|
1.6 mL
Standard Deviation 42.17
|
42.0 mL
Standard Deviation 51.89
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom watts was measured
Change in watts from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=8 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=7 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=8 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Watts
|
9.6 watts
Standard Deviation 14.15
|
13.9 watts
Standard Deviation 12.48
|
5.4 watts
Standard Deviation 10.03
|
4.4 watts
Standard Deviation 11.87
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom temperature was measured
Change in temperature as measured by units of Celsius from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=8 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Temperature (°C)
|
-0.3 °C
Standard Deviation 0.54
|
0.2 °C
Standard Deviation 0.42
|
0.1 °C
Standard Deviation 0.28
|
0.0 °C
Standard Deviation 0.67
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom PR interval was measured
Change in PR interval as measured by ECG in milliseconds from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=8 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in ECG-PR Interval (Msec)
|
-3.2 msec
Standard Deviation 7.77
|
8.3 msec
Standard Deviation 7.05
|
9.1 msec
Standard Deviation 9.55
|
-1.6 msec
Standard Deviation 15.61
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom QRS complex was measured
Change in QRS complex as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in ECG-QRS Complex (Msec)
|
1.2 msec
Standard Deviation 7.14
|
2.3 msec
Standard Deviation 6.56
|
-2.2 msec
Standard Deviation 8.86
|
0.8 msec
Standard Deviation 5.78
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom QT interval was measured
Change in QT interval as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in ECG-QT Interval (Msec)
|
-6.0 msec
Standard Deviation 30.53
|
-4.8 msec
Standard Deviation 12.94
|
-16.7 msec
Standard Deviation 81.02
|
-1.3 msec
Standard Deviation 18.49
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom QTc interval was measured
Change in QTc interval as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in ECG-QTc Interval (Msec)
|
3.4 msec
Standard Deviation 20.17
|
1.3 msec
Standard Deviation 20.24
|
-23.2 msec
Standard Deviation 77.53
|
6.7 msec
Standard Deviation 17.28
|
SECONDARY outcome
Timeframe: Days 1-5 and Day 7.Population: Participants for whom CSSR was measured.
Number of participants with suicide ideation, suicidal behavior, or non-suicidal self-injurious behavior post-screening as measured on Days 1-5, and Day 7 on the Columbia Suicide Severity Rating Scale (CSSRS). A yes/no binary response is utilized in the following ten categories: 1 - Wish to be Dead; 2 - Non-specific Active Suicidal Thoughts; 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5 - Active Suicidal Ideation with Specific Plan and Intent; 6 - Preparatory Acts or Behavior; 7 - Aborted Attempt; 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); 10 - Completed Suicide. A yes/no binary response is also utilized in assessing self-injurious behavior without suicidal intent. A lower score means a better outcome whereas a higher score means a worse outcome.
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Number of Participants Who Had Suicide Ideation, Suicidal Behavior, or Non-suicidal Self-injurious Behavior Post-screening.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom creatine phosphokinase was measured
Change in Creatine Phosphokinase as measured by IU/L from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Creatine Phosphokinase (IU/L)
|
-24.8 IU/L
Standard Deviation 25.10
|
-161.7 IU/L
Standard Deviation 176.49
|
-101.2 IU/L
Standard Deviation 149.07
|
-154.9 IU/L
Standard Deviation 232.99
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom Alanine aminotransferase was measured
Change in Alanine aminotransferase (ALT) as measured by (U/L) from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Alanine Aminotransferase (ALT) (U/L)
|
19.3 U/L
Standard Deviation 42.24
|
-3.0 U/L
Standard Deviation 4.92
|
-5.3 U/L
Standard Deviation 3.28
|
1.1 U/L
Standard Deviation 5.80
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom aspartate aminotransferase was measured
Change in aspartate aminotransferase (AST) as measured by U/L from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Aspartate Aminotransferase (AST) (U/L)
|
5.6 U/L
Standard Deviation 9.93
|
-2.2 U/L
Standard Deviation 10.38
|
-12.6 U/L
Standard Deviation 18.08
|
-4.4 U/L
Standard Deviation 13.07
|
SECONDARY outcome
Timeframe: Baseline, Day 5Population: Participants for whom eosinophils was measured
Change in eosinophils as measured by (10\^9 cells/L) from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Outcome measures
| Measure |
Low Dose
n=9 Participants
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 Participants
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=8 Participants
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 Participants
Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Change in Eosinophils (10^9 Cells/L)
|
0.06 10^9 cells/L
Standard Deviation 0.073
|
0.08 10^9 cells/L
Standard Deviation 0.097
|
-0.01 10^9 cells/L
Standard Deviation 0.064
|
0.04 10^9 cells/L
Standard Deviation 0.088
|
Adverse Events
Low Dose
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Intermediate Dose
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
High Dose
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low Dose
n=9 participants at risk
MTP-131 (low dose) 0.01 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Intermediate Dose
n=9 participants at risk
MTP-131 (intermediate dose) 0.10 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
High Dose
n=9 participants at risk
MTP-131 (high dose) 0.25 mg/kg/hour administered as single day intravenous infusion over 2 hours for 5 days
|
Placebo
n=9 participants at risk
Placebo: Placebo Comparator (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
11.1%
1/9 • 7 days
|
11.1%
1/9 • 7 days
|
22.2%
2/9 • 7 days
|
22.2%
2/9 • 7 days
|
|
Nervous system disorders
Dizziness
|
22.2%
2/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/9 • 7 days
|
22.2%
2/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Gastrointestinal disorders
Flatulence
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
General disorders
Injection site bruising
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
General disorders
Thirst
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
General disorders
Vessel puncture site haemorrhage
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Infections and infestations
Nasopharyngitis
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Infections and infestations
Viral upper respiratory tract
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Injury, poisoning and procedural complications
Contusion
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Investigations
Eosinophil count increased
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Investigations
Hepatic enzyme increased
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Investigations
Liver function test increased
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Metabolism and nutrition disorders
Increased appetite
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Nervous system disorders
Somnolence
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Nervous system disorders
Migraine
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Nervous system disorders
Myoclonus
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Nervous system disorders
Presyncope
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Skin and subcutaneous tissue disorders
Hyperhydrosis
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Skin and subcutaneous tissue disorders
Skin tightness
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Vascular disorders
Flushing
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
|
Vascular disorders
Hypotension
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Vascular disorders
Pallor
|
0.00%
0/9 • 7 days
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
|
Vascular disorders
Phlebitis
|
11.1%
1/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
0.00%
0/9 • 7 days
|
Additional Information
Jim Carr PharmD Chief Clinical Development Officer
Stealth BioTherapeutics Inc.
Phone: 617-600-6888
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60