Amyotrophic Lateral Sclerosis (ALS)
Conditions
Keywords
Amyotrophic lateral sclerosis (ALS)
Brief summary
This is a long-term, double-blind, placebo-controlled study of MCI-186 to treat ALS. This study is the long-term extension of Study NCT00330681; Study NCT00330681 is a Phase 3, randomized, double-blind, placebo control, parallel assignment, 24-week study in the treatment of ALS. The objectives of this study are to assess the efficacy and safety of long-term intermittent therapy with 60 mg MCI-186 to ALS patients.
Interventions
DRUGMCI-186
Two ampoules (60 mg) of MCI-186 injection are intravenously administered once a day for 10 days during 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days ) - observation (14 days) cycle is repeated eight times.
Two ampoules of placebo injection are intravenously administered once a day for 10 days during 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated eight times.
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who ware completed drug administration without discontinuation in the preceding confirmatory study NCT00330681.
Exclusion criteria
* Patients with such complications as Parkinson's disease, schizophrenia, dementia, renal failure, or other severe complication, and patients who have the anamnesis of hypersensitivity to edaravone. * Patients whose creatinine clearance is 50mL/min or less at the time of completion of drug administration in the study NCT00330681. * Pregnant, lactating, and probably pregnant patients, and patients who want to become pregnant, and patients who can not agree to contraception. * Patients who are participating in other clinical trials except the study NCT00330681. * In addition to the above
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | baseline (seventh cycle) and at 24 week (twelfth cycle) | 0=worst; 48=best To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death or a Specified State of Disease Progression | 24 weeks (from seventh cycle to twelfth cycle) | Any of "death, disability of independent ambulation, loss of upper arm function, tracheotomy, use of respirator, and use of tube feeding" was defined as an event. |
| Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | baseline (seventh cycle) and at 24 week (twelfth cycle) | To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed. |
| Percentage of Participants With Adverse Events | 36 weeks (from seventh cycle to fifteenth cycle) | — |
| Percentage of Participants With Adverse Drug Reactions | 36 weeks (from seventh cycle to fifteenth cycle) | — |
| Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | 36 weeks (from seventh cycle to fifteenth cycle) | — |
| Percentage of Participants With Abnormal Changes in Sensory Examinations | 36 weeks (from seventh cycle to fifteenth cycle) | — |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-186 - Placebo of MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion | 45 |
| MCI-186 - MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion | 48 |
| Placebo of MCI-186 - MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion | 88 |
| Total | 181 |
Baseline characteristics
| Characteristic | MCI-186 - Placebo of MCI-186 | MCI-186 - MCI-186 | Placebo of MCI-186 - MCI-186 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 19 Participants | 26 Participants | 52 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 29 Participants | 62 Participants | 129 Participants |
| Sex: Female, Male Female | 12 Participants | 22 Participants | 31 Participants | 65 Participants |
| Sex: Female, Male Male | 33 Participants | 26 Participants | 57 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| other Total, other adverse events | 43 / 45 | 43 / 48 | 74 / 88 |
| serious Total, serious adverse events | 13 / 45 | 25 / 48 | 39 / 88 |
Outcome results
Primary
Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks
0=worst; 48=best To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed.
Time frame: baseline (seventh cycle) and at 24 week (twelfth cycle)
Population: 1 patient with diseases other than ALS and 4 patients with missing data were excluded from the FAS in the MCI-186 - Placebo of MCI-186group.~5 patients with missing data were excluded from the FAS in the MCI-186 - MCI-186 group.~14 patients with missing data were excluded from the FAS in the Placebo of MCI-186 - MCI-186 group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 - Placebo of MCI-186 | Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | -5.5 units on a scale | Standard Deviation 4.6 |
| MCI-186 - MCI-186 | Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | -4.2 units on a scale | Standard Deviation 4 |
| Placebo of MCI-186 - MCI-186 | Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | -5.4 units on a scale | Standard Deviation 4.5 |
Secondary
Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks
To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed.
Time frame: baseline (seventh cycle) and at 24 week (twelfth cycle)
Population: 1 patient with diseases other than ALS and 4 patients with missing data were excluded from the FAS in the MCI-186 - Placebo of MCI-186group.~6 patients with missing data were excluded from the FAS in the MCI-186 - MCI-186 group.~19 patients with missing data were excluded from the FAS in the Placebo of MCI-186 - MCI-186 group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 - Placebo of MCI-186 | Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | -10.6 percentage of FVC | Standard Deviation 13.16 |
| MCI-186 - MCI-186 | Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | -12.91 percentage of FVC | Standard Deviation 14.97 |
| Placebo of MCI-186 - MCI-186 | Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | -10.54 percentage of FVC | Standard Deviation 13.21 |
Secondary
Number of Participants With Death or a Specified State of Disease Progression
Any of death, disability of independent ambulation, loss of upper arm function, tracheotomy, use of respirator, and use of tube feeding was defined as an event.
Time frame: 24 weeks (from seventh cycle to twelfth cycle)
Population: 1 patient with diseases other than ALS was excluded from the FAS in the MCI-186 - Placebo of MCI-186 group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MCI-186 - Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | use of respirator | 0 Participants |
| MCI-186 - Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | use of tube feeding | 1 Participants |
| MCI-186 - Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | death | 1 Participants |
| MCI-186 - Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | tracheotomy | 0 Participants |
| MCI-186 - Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | loss of upper arm function | 3 Participants |
| MCI-186 - Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | disability of independent ambulation | 8 Participants |
| MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | disability of independent ambulation | 11 Participants |
| MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | use of respirator | 1 Participants |
| MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | death | 1 Participants |
| MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | tracheotomy | 0 Participants |
| MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | use of tube feeding | 1 Participants |
| MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | loss of upper arm function | 5 Participants |
| Placebo of MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | use of tube feeding | 8 Participants |
| Placebo of MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | death | 1 Participants |
| Placebo of MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | disability of independent ambulation | 20 Participants |
| Placebo of MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | loss of upper arm function | 7 Participants |
| Placebo of MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | tracheotomy | 2 Participants |
| Placebo of MCI-186 - MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | use of respirator | 2 Participants |
Secondary
Percentage of Participants With Abnormal Changes in Sensory Examinations
Time frame: 36 weeks (from seventh cycle to fifteenth cycle)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Staggering | 0 percentage of participant |
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Numbness | 0 percentage of participant |
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Vibratory sensation | 0 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Staggering | 2.1 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Numbness | 0 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Vibratory sensation | 0 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Numbness | 0 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Vibratory sensation | 0 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Staggering | 2.3 percentage of participant |
Secondary
Percentage of Participants With Adverse Drug Reactions
Time frame: 36 weeks (from seventh cycle to fifteenth cycle)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Adverse Drug Reactions | 4.4 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Adverse Drug Reactions | 10.4 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Adverse Drug Reactions | 10.2 percentage of participant |
Secondary
Percentage of Participants With Adverse Events
Time frame: 36 weeks (from seventh cycle to fifteenth cycle)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Adverse Events | 97.8 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Adverse Events | 91.7 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Adverse Events | 92 percentage of participant |
Secondary
Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group
Time frame: 36 weeks (from seventh cycle to fifteenth cycle)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | Alanine aminotransferase | 0 percentage of participant |
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | White blood cell count | 11.1 percentage of participant |
| MCI-186 - Placebo of MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | Urinary glucose | 0 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | Alanine aminotransferase | 6.3 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | White blood cell count | 4.2 percentage of participant |
| MCI-186 - MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | Urinary glucose | 6.3 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | White blood cell count | 10.2 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | Urinary glucose | 3.4 percentage of participant |
| Placebo of MCI-186 - MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | Alanine aminotransferase | 4.5 percentage of participant |