Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00415519
• Collaborator: (none)
• Enrollment: 25
• Arms: 2
• Duration (Months): 19

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of 60mg of MCI-186 via intravenous drip once a day in patients with ALS whose severity is classified as grade III, based on the changes in the revised ALS functional rating scale (ALSFRS-R) scores after 24 weeks administration in double-blind, placebo-controlled manner. And in addition, this study will be performed to examine the safety of MCI-186 to ALS patients who met severity classification III.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: MCI-186; Drug: Placebo of MCI-186	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Exploratory Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (Severity Classification III) in Double-Blind, Parallel-Group, Placebo-Controlled Manner
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: MCI-186; Two ampoules (60 mg) of MCI-186 injection are intravenously administered once a day, for successive 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).; Other Names: Edaravone Radicut
Placebo Comparator: 2	Drug: Placebo of MCI-186; Two ampoules of Placebo injection are intravenously administered once a day, for successive 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks [baseline and 24 weeks]

   No primary endpoint was used, because various exploratory analyses were performed. 0=worst; 48=best

2. Death or a Specified State of Disease Progression [24 weeks]

   No primary endpoint was used, because various exploratory analyses were performed. 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.

3. Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks [baseline and 24 weeks]

   No primary endpoint was used, because various exploratory analyses were performed.

4. Percentage of Participants With Adverse Events [24 weeks]

   No primary endpoint was used, because various exploratory analyses were performed.

5. Percentage of Participants With Adverse Drug Reactions [24 weeks]

   No primary endpoint was used, because various exploratory analyses were performed.

6. The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients [24 weeks]

   No primary endpoint was used, because various exploratory analyses were performed.

7. Percentage of Participants With Abnormal Changes in Sensory Examinations [24 weeks]

   No primary endpoint was used, because various exploratory analyses were performed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who are defined as "definite ALS," "probable ALS" or "probable-laboratory-supported ALS," met diagnostic criteria revised EL Escorial for Airlie House.

• Patients who cannot take at least one action of eating a meal, excreting, or moving with oneself alone, and need assistance in everyday life.

• Patients whose progress of the condition during 12 weeks before administration meet other requirements.

Exclusion Criteria:

• Patients judged to be inadequate to participate in this study by their physician, because those patients' general condition deteriorated to the point that they need to be hospitalized for severe hepatic disease, sever heart disease, sever renal disease and so on, or they need to be administered antibiotics to infection.

• Patients who complain the difficulty in breathing caused by deteriorating the respiratory function.

• 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.

• Pregnant, lactating, and probably pregnant patients, and patients who want to become pregnant, and patients who can not agree to contraception.

• Patients who have been administered other investigational products within 12 weeks before consent, or who are participating in other clinical trials at present.

• In addition to the above exclusion criteria, patients judged to be inadequate to participate in this study by their physician.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Principal Investigator: Koji Abe, professor, Graduate School of Medicine and Dentistry, Okayama University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00415519
• Other Study ID Numbers: MCI186-18
• First Posted: Dec 25, 2006
• Last Update Posted: Dec 20, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Mitsubishi Tanabe Pharma Corporation: Amyotrophic lateral sclerosis; free radical scavenger
• Additional relevant MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Edaravone

Study Results

Participant Flow

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Period Title: Overall Study
STARTED	13	12
COMPLETED	9	12
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	MCI-186	Placebo of MCI-186	Total
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min	Total of all reporting groups
Overall Participants	13	12	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 84.6%	10 83.3%	21 84%
>=65 years	2 15.4%	2 16.7%	4 16%
Sex: Female, Male (Count of Participants)
Female	6 46.2%	6 50%	12 48%
Male	7 53.8%	6 50%	13 52%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks
Description	No primary endpoint was used, because various exploratory analyses were performed. 0=worst; 48=best
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Measure Participants	13	12
Least Squares Mean (Standard Error) [units on a scale]	-6.52 (1.78)	-6 (1.83)

2. Primary Outcome

Title	Death or a Specified State of Disease Progression
Description	No primary endpoint was used, because various exploratory analyses were performed. 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Measure Participants	13	12
death	1	0
disability of independent ambulation	4	2
loss of upper arm function	1	2
tracheotomy	0	0
use of respirator	0	0
use of tube feeding	1	0

3. Primary Outcome

Title	Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks
Description	No primary endpoint was used, because various exploratory analyses were performed.
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

"1 patient with missing value at baseline" was excluded from the FAS in the MCI-186 group.

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Measure Participants	12	12
Least Squares Mean (Standard Error) [percentage of FVC]	-18.75 (4.58)	-15.69 (4.58)

4. Primary Outcome

Title	Percentage of Participants With Adverse Events
Description	No primary endpoint was used, because various exploratory analyses were performed.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Measure Participants	13	12
Number [percentage of participants]	92.3 710%	100 833.3%

5. Primary Outcome

Title	Percentage of Participants With Adverse Drug Reactions
Description	No primary endpoint was used, because various exploratory analyses were performed.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Measure Participants	13	12
Number [percentage of participants]	23.1 177.7%	8.3 69.2%

6. Primary Outcome

Title	The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients
Description	No primary endpoint was used, because various exploratory analyses were performed.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Measure Participants	13	12
White blood cell count (WBC)	23.1 177.7%	8.3 69.2%
Other laboratory tests except for WBC	0 0%	0 0%

7. Primary Outcome

Title	Percentage of Participants With Abnormal Changes in Sensory Examinations
Description	No primary endpoint was used, because various exploratory analyses were performed.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

A note: Each three patients of both groups did not have data to Staggering due to data missing. Therefore, concerning staggering, the number of participants analysed are 10 in the MCI-186 group and 9 in the placebo of MCI-186 group.

Arm/Group Title	MCI-186	Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min	MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
Measure Participants	13	12
Numbness	0 0%	0 0%
Staggering	10 76.9%	0 0%
Vibratory sensation	0 0%	0 0%

Adverse Events

Arm/Group Title	MCI-186		Placebo of MCI-186
Arm/Group Description	MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min		MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min
All Cause Mortality
	MCI-186		Placebo of MCI-186
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MCI-186		Placebo of MCI-186
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/13 (23.1%)		2/12 (16.7%)
Gastrointestinal disorders
Dysphagia	2/13 (15.4%)		0/12 (0%)
General disorders
Gait disturbance	1/13 (7.7%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder	1/13 (7.7%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/13 (7.7%)		0/12 (0%)
Respiratory failure	1/13 (7.7%)		0/12 (0%)
Vascular disorders
Pelvic venous thrombosis	0/13 (0%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	MCI-186		Placebo of MCI-186
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		12/12 (100%)
Ear and labyrinth disorders
Vertigo positional	1/13 (7.7%)		0/12 (0%)
Eye disorders
Abnormal sensation in eye	0/13 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Constipation	2/13 (15.4%)		0/12 (0%)
Diarrhoea	3/13 (23.1%)		1/12 (8.3%)
Dyschezia	0/13 (0%)		3/12 (25%)
Gingivitis	1/13 (7.7%)		0/12 (0%)
Proctalgia	0/13 (0%)		1/12 (8.3%)
Stomach discomfort	0/13 (0%)		1/12 (8.3%)
Stomatitis	0/13 (0%)		3/12 (25%)
Toothache	0/13 (0%)		1/12 (8.3%)
Vomiting	0/13 (0%)		1/12 (8.3%)
General disorders
Abasia	0/13 (0%)		1/12 (8.3%)
Feeling cold	1/13 (7.7%)		0/12 (0%)
Gait disturbance	3/13 (23.1%)		1/12 (8.3%)
Impaired healing	1/13 (7.7%)		0/12 (0%)
Thirst	0/13 (0%)		1/12 (8.3%)
Infections and infestations
Acarodermatitis	1/13 (7.7%)		0/12 (0%)
Cystitis	0/13 (0%)		1/12 (8.3%)
Nasopharyngitis	2/13 (15.4%)		2/12 (16.7%)
Oral herpes	1/13 (7.7%)		0/12 (0%)
Pharyngitis	0/13 (0%)		1/12 (8.3%)
Sinusitis	0/13 (0%)		1/12 (8.3%)
Tinea pedis	1/13 (7.7%)		0/12 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/13 (0%)		1/12 (8.3%)
Contusion	1/13 (7.7%)		1/12 (8.3%)
Joint sprain	0/13 (0%)		2/12 (16.7%)
Investigations
Blood urine present	0/13 (0%)		1/12 (8.3%)
Glucose urine present	1/13 (7.7%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/13 (0%)		1/12 (8.3%)
Muscular weakness	1/13 (7.7%)		0/12 (0%)
Musculoskeletal disorder	0/13 (0%)		1/12 (8.3%)
Musculoskeletal pain	0/13 (0%)		1/12 (8.3%)
Myalgia	0/13 (0%)		2/12 (16.7%)
Pain in extremity	0/13 (0%)		1/12 (8.3%)
Nervous system disorders
Headache	3/13 (23.1%)		2/12 (16.7%)
Post herpetic neuralgia	0/13 (0%)		1/12 (8.3%)
Tension headache	0/13 (0%)		1/12 (8.3%)
Psychiatric disorders
Anxiety disorder	0/13 (0%)		1/12 (8.3%)
Depression	1/13 (7.7%)		0/12 (0%)
Insomnia	1/13 (7.7%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/13 (7.7%)		0/12 (0%)
Cough	0/13 (0%)		1/12 (8.3%)
Oropharyngeal pain	0/13 (0%)		1/12 (8.3%)
Productive cough	0/13 (0%)		1/12 (8.3%)
Respiratory disorder	1/13 (7.7%)		0/12 (0%)
Sputum retention	1/13 (7.7%)		0/12 (0%)
Upper respiratory tract inflammation	3/13 (23.1%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/13 (0%)		1/12 (8.3%)
Erythema	1/13 (7.7%)		0/12 (0%)
Haemorrhage subcutaneous	0/13 (0%)		1/12 (8.3%)
Pruritus	2/13 (15.4%)		1/12 (8.3%)
Rash	2/13 (15.4%)		0/12 (0%)
Seborrhoeic dermatitis	0/13 (0%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.