Trial Outcomes & Findings for Trial of Safety and Efficacy of Rasagiline in Patients With Amyotrophic Lateral Sclerosis (ALS) (NCT NCT01232738)

NCT ID: NCT01232738

Last Updated: 2018-05-18

Results Overview

The primary outcome measure is the difference in the rate of decline in function, as detected by the ALS Functional Rating Scale - Revised (ALSFRS-R) in patients taking rasagiline compared to a database of patients from randomized clinical trials conducted during 1997-2007. Minimum score is 0 (no function) to Maximum score is 48 (normal function)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 36 participants
• Primary outcome timeframe: up to 12 months
• Results posted on: 2018-05-18

Participant Flow

Participant milestones

Measure	Rasagiline Open label study of rasagiline at 2 mg daily for 12 months
Overall Study STARTED	36
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Measure	Rasagiline Open label study of rasagiline at 2 mg daily for 12 months
Overall Study Death	3
Overall Study Physician Decision	2
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	2
Overall Study Adverse Event	5

Baseline Characteristics

Trial of Safety and Efficacy of Rasagiline in Patients With Amyotrophic Lateral Sclerosis (ALS)

Baseline characteristics by cohort

Measure	Rasagiline n=36 Participants Open label study of 2 mg rasagiline daily
Age, Continuous	61.1 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Region of Enrollment Canada	3 Participants n=5 Participants
Region of Enrollment United States	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 12 months

Population: The placebo arm are from the randomized, controlled studies in ALS performed during 2004-2010, corrected for symptom duration.

The primary outcome measure is the difference in the rate of decline in function, as detected by the ALS Functional Rating Scale - Revised (ALSFRS-R) in patients taking rasagiline compared to a database of patients from randomized clinical trials conducted during 1997-2007. Minimum score is 0 (no function) to Maximum score is 48 (normal function)

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=36 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control n=478 Participants Change in slope in the Historical Placebo Control group
Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)	-1.20 units on a scale Standard Error 0.14	-0.94 units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: up to 12 months

Population: Failure was defined as death, endotracheal intubation, tracheostomy-assisted ventilation, or use of noninvasive ventilation 23 hours/day for 14 days or more. It is defined in years.

This group is defined as death, endotracheal intubation, tracheostomy-assisted ventilation or use of noninvasive ventilation >= 23 hours/day for 14 days or more.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=36 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control n=203 Participants Change in slope in the Historical Placebo Control group
Difference in Time to Treatment Failure	0.9367 years Interval 0.7682 to 0.9839	0.8963 years Interval 0.8438 to 0.9318

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months, 12 months

Population: Only 14 subjects that completed the study were able to have this biomarker analyzed.

The 12 month change in mitochondrial biomarkerJC-1 red/green fluorescence ratio. We measured at baseline, 6 months and 12 months.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=14 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control Change in slope in the Historical Placebo Control group
Change in JC-1 Mitochondrial Biomarkers	1.92 ratio Interval 1.14 to 2.7	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months, 12 months

Population: Only 17 subjects that completed the study were able to have this biomarker analyzed.

The 12 month change in mitochondrial biomarkerMitotracker. We measured at baseline, 6 months and 12 months.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=17 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control Change in slope in the Historical Placebo Control group
Change in Mitotracker Mitochondrial Biomarkers	54.14 Relative Fluorescent Intensity Interval 31.47 to 76.81	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months, 12 months

Population: Only 17 subjects that completed the study were able to have this biomarker analyzed.

The 12 month change in mitochondrial biomarker Annexin V %. We measured at baseline, 6 months and 12 months.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=17 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control Change in slope in the Historical Placebo Control group
Change in Percent Annexin V Mitochondrial Biomarkers	-6.67 Annexin V % Interval -20.3 to 6.7	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months, 12 months

Population: Only 10 subjects that completed the study were able to have this biomarker analyzed.

The 12 month change in mitochondrial biomarker BCL2/BAX. We measured at baseline, 6 months and 12 months.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=10 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control Change in slope in the Historical Placebo Control group
Change in BCL2/BAX Mitochondrial Biomarkers	0.24 Ratio Interval 0.24 to 0.27	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months, 12 months

Population: Only 17 subjects that completed the study were able to have this biomarker analyzed.

The 12 month change in mitochondrial biomarker Oxygen Radical Antioxidant Capacity. We measured at baseline, 6 months and 12 months.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=17 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control Change in slope in the Historical Placebo Control group
Change in ORAC Mitochondrial Biomarkers	1028.70 Trolox equivalents Interval 681.09 to 1376.31	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months, 12 months

Population: Only 17 subjects that completed the study were able to have this biomarker analyzed.

The 12 month change in mitochondrial biomarker Oxygen Radical Antioxidant Capacity. We measured at baseline, 6 months and 12 months.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=17 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control Change in slope in the Historical Placebo Control group
Change in ORAC Mitochondrial Biomarkers	1028.70 umol Trolox equivalents Interval 681.09 to 1376.31	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months, 12 months

Population: Only 17 subjects that completed the study were able to have this biomarker analyzed.

The 12 month change in mitochondrial biomarker Oxygen Radical Antioxidant Capacity. We measured at baseline, 6 months and 12 months.

Outcome measures

Measure	ALSRFS-R Slope - Rasagiline n=17 Participants Change in ALSRFS-R at 12 months	ALSFRS-R - Historical Placebo Control Change in slope in the Historical Placebo Control group
Change in ORAC Mitochondrial Biomarkers	1028.70 Trolox equivalents Interval 681.09 to 1376.31	—

Adverse Events

Rasagiline

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rasagiline n=36 participants at risk Treated for 12 months with rasagiline 2mg orally, once daily. rasagiline: rasagiline 2 mg daily for 12 months
Injury, poisoning and procedural complications Fracture	2.8% 1/36 • Number of events 1

Other adverse events

Measure	Rasagiline n=36 participants at risk Treated for 12 months with rasagiline 2mg orally, once daily. rasagiline: rasagiline 2 mg daily for 12 months
Skin and subcutaneous tissue disorders Alopecia	2.8% 1/36 • Number of events 1
Psychiatric disorders Anxiety	5.6% 2/36 • Number of events 2
Gastrointestinal disorders Constipation	5.6% 2/36 • Number of events 2
Blood and lymphatic system disorders Dizziness	8.3% 3/36 • Number of events 3
Nervous system disorders Headache	5.6% 2/36 • Number of events 2
Blood and lymphatic system disorders Hypertension	2.8% 1/36 • Number of events 1
Gastrointestinal disorders nausea	11.1% 4/36 • Number of events 4
General disorders Xerostomia	2.8% 1/36 • Number of events 1
Hepatobiliary disorders Lab abnormality (elevated ALT)	2.8% 1/36 • Number of events 1

Additional Information

Yunxia Wang

UKansasMCRI

Phone: 913-588-6970

Email: ywang@kumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place