MITOTARGET: Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00868166
• Collaborator: European Commission (Other)
• Enrollment: 512
• Locations: 15
• Arms: 2
• Actual Duration (Months): 29
• Patients Per Site: 34.1
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of the assay is to assess the safety and the efficacy of TRO19622 330 mg QD as add-on therapy to riluzole 50 mg bid in the treatment of patients suffering from ALS, as compared to placebo, assessed by the 18-month survival rate.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Olesoxime; Drug: Placebo Comparator; Drug: Riluzole	Phase 3

Detailed Description

A stand alone treatment with TRO19622 is not acceptable for ethical reasons. Riluzole is an approved and widely used ALS treatment in the European community, in Japan and in the USA.

Therefore, in this study, TRO19622 will be assessed as add-on to riluzole in patients suffering from ALS.

At the start of the study, patients will be randomized to one of two groups : TRO19622 (330 mg QD or placebo (once a day).

Each treatment will be administered for 18 months under double-blind conditions. The product under evaluation will be administered to patients receiving the standard of care for ALS, including riluzole.

Riluzole dosage (50 mg bid) must be stable and well tolerated for at least one month prior to inclusion into the study.

After the double-blind period, open-label administration of TRO19622 will be allowed for safety and survival assessments and until efficacy results are available.

A separate open-label protocol will be written 6 months after the randomization of the last patient into the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 512 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Phase II/III, Multicenter, Randomized, Parallel Group, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of TRO19622 in Amyotrophic Lateral Sclerosis (ALS) Patients Treated With Riluzole
• Actual Study Start Date: Apr 30, 2009
• Actual Primary Completion Date: Sep 30, 2011
• Actual Study Completion Date: Sep 30, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Olesoxime 2 Capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid	Drug: Olesoxime; 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid; Other Names: TRO19622 ; Drug: Riluzole; Riluzole given as add-on therapy 50mg bid; Other Names: Rilutek
Placebo Comparator: Placebo Comparator 2 Capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid	Drug: Placebo Comparator; 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid; Other Names: Placebo ; Drug: Riluzole; Riluzole given as add-on therapy 50mg bid; Other Names: Rilutek

Outcome Measures

Primary Outcome Measures

1. Overall Survival Rate at 18 Months [From the date of randomization until the date of death or last follow-up censored at 18 months (548 days)]

   Overall survival was defined from the date of randomization until the date of death (event) or last known alive date (censored). If the death date was after 18 months, the participant was censored at 18 months (548 days). Participants still alive at or after 18 months were censored at 18 months/ 548 days. All data over the 18-month follow-up period after randomization, and participant survival status at the 18-month follow-up visit for participants who withdrew prematurely from the study for reasons other than death were included.

Secondary Outcome Measures

1. Percentage of Participants With Failure Over 18 Months [From randomization to the time of the first event to consider at 18 months (548 days)]

   Time to failure was defined as the time from randomization to the time of the first event to consider (Tracheostomy, invasive ventilation [IV] or non invasive ventilation [NIV])

2. Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) [Inclusion, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18]

   The ALSFRS-R is an ordinal rating scale (0 through 4) used to determine the ALS participant's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score from four sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). Total scores range from 0 (most impaired) to 48 (normal ability).

3. Percentage of Participants With a Global ALS FRS-R Score of <30 or Death [Month 18 (548 days)]

   Percentage of participants with a global ALS FRS-R score of < 30 or death was estimated using the Kaplan-Meier method in the ITT, with a two-tailed log-rank, both stratified by site of onset (bulbar or spinal) and non-stratified. The ALSFRS-R is an ordinal rating scale (0 through 4) used to determine the ALS participant's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score from four sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). Total scores range from 0 (most impaired) to 48 (normal ability).

4. Slow Vital Capacity (SVC) Percent Predicted [Baseline, Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18]

   SVC as a percent of the predicted value was evaluated and reported.

5. Percentage of Participants With SVC Percent Predicted <70% or Had Died Over 18 Months [Month 18 (548 days)]

6. Global Score of Manual Muscle Testing (MMT) of 34 Muscle Groups [Inclusion, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18]

   MMT score involved the examination of 30 items. These 30 items are scored from 0 (no trace of contraction) to 5 (normal power at first try). The global score is the sum of the item scores and can range from 0 to 150. Higher score indicates some power.

7. The Single-Item Mc Gill Quality of Life Scale [Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18]

   The single-item McGill quality of life scale evaluated the following question "Considering all parts of my life - physical, emotional, social, spiritual, and financial - over the past two (2) days, the quality of my life has been…"as a score of 1 to 10 on a visual analog scale where 0 is very bad and 10 is excellent.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with sporadic or familial Amyotrophic Lateral Sclerosis

• Patients with a clinical diagnosis of laboratory-supported probable, probable, or definite ALS according to the modified El Escorial criteria8.

• Have signed an Informed Consent to participate to the trial before any study related procedure has taken place.

• Be of age >18 (exclusive) and < 80 years (inclusive).

• If a female, not lactating, has a negative pregnancy test and agrees to use an effective method of birth control.

• Onset of ALS Symptoms (weakness) for more than 6 months (inclusive) and less than 36 months(inclusive).

• Slow vital capacity (SVC), measured three times, one of the measure being >/= 70% of that predicted.

• Treated with riluzole at the stable dose of 50 mg bid for at least 30 days before enrolment.

Exclusion Criteria:

• Tracheostomy, invasive ventilation, or non invasive positive pressure ventilation (NIPPV).

• Gastrostomy.

• Evidence of major psychiatric disorder or clinically evident dementia.

• Diagnosis of a neurodegenerative disease in addition to ALS.

• Have a current medication that could interfere with TRO19622 pharmacokinetics: tamoxifene.

• Have current medications that could interfere with TRO19622 absorption such as ezetimibe, bile salts chelators (cholesteramine), fibrates, phytosterols, niacin (vitamin B3),fish oils. Have a current medication of lipid lowering agents other than statins.

• Known hypersensitivity to any component of the study drug.

• Patients with known intolerance or contra-indication to riluzole.

• Have a recent history (within the previous 6 months) or current evidence of alcohol or drug abuse.

• Have concurrent unstable disease involving any system eg, carcinoma other than basal cell carcinoma, any cardiac dysrhythmia, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency, angina symptoms, current symptoms of Coronary Artery Disease, or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation.

. In Germany: Have any cardiac dysrhythmia, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency, angina symptoms, current symptoms of Coronary Artery Disease or any cardiovascular illness known or identified at the screening or inclusion visits, or have concurrent unstable disease involving any system eg, carcinoma other than basal cell carcinoma or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation.

• Having a baseline QTc (Bazett) > 450 msec for males and > 470 msec for females.

• Patients with known hepatitis B/C or HIV positive serology.

• Be pregnant female or lactating.

• Have renal impairment defined as blood creatinine > 1:5 X upper limit of normal.

• Have hepatic impairment and/or liver enzymes (ALAT or ASAT) > 3 X ULN.

• Hemostasis disorders or current treatment with oral anticoagulants.

• Be possibly dependent on the Investigator or the Sponsor (eg, including, but not limited to, affiliated employee).

• Participated in any other investigational drug or therapy study with a non approved medication, within the previous 3 months.

• Patients without Social Security Insurance (France).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Gasthuisberg - Dept Neurology - Herestraat 49	Leuven		Belgium	3000
2	HCL Hôpital Neurologique et Neurochirurgical Pierre Wertheimer - Neurologie C et Laboratoire d'électromyographie - 59, boulevard Pinel	Bron Cedex		France	69677
3	CHRU de LILLE - Hôpital Roger Salengro - Centre SLA-MMN - Sce de Neurologie et Pathologie du Mouvement	Lille		France	59037
4	Centre SLA Limoges - Service de Neurologie	Limoges		France	87042
5	Hôpital La Timone - Service Neurologie et Maladies Neuromusculaires	Marseille		France	13005
6	Clinique du Motoneurone - Sce d'Explorations Neurologiques - Hôpital Gui de Chauliac	Montpellier		France	34295
7	CHU de Nice - Hôpital de l'Archet 1 - Centre de Référence pour les Maladies Neuromusculaires et la SLA	Nice		France	06202
8	Groupe Hospitalier PITIE-SALPETRIERE - Fédération des Maladies du Système Nerveux	Paris		France	75013
9	Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Neurologische Poliklinik Ambulanz für ALS und andere Motoeneuronenerkrankungen	Berlin		Germany	13353
10	Universitätsklinik und Poliklinik für Neurologie - Martin-Luther-Universität Halle-Wittenberg	Halle		Germany	06097
11	Neurologische Klinik Medizinische Hochschule	Hannover		Germany	D-30623
12	Universitäts- und Rehabilitationskliniken Ulm (RKU) - Neurologische Universitätsklinik	Ulm		Germany	89081
13	Hospital Carlos III - Unidad de ELA - Sinesio Delgado, 10	Madrid		Spain	28029
14	King's MND Care and Research Center - Academic Neurosciences Building PO Box 41 Institute of Psychiatry	London		United Kingdom	SE58AF
15	Academic Neurology Unit - University of Sheffield - Section of Neuroscience - Division of Genomic Medicine - School of Medicine and Biomedical Sciences	Sheffield		United Kingdom	S10 2RX

Sponsors and Collaborators

• Hoffmann-La Roche
• European Commission

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00868166
• Other Study ID Numbers: WN29853; EudraCT Number:2008-007320-25; TRO19622 CL E Q 1015-1
• First Posted: Mar 24, 2009
• Last Update Posted: Feb 25, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Hoffmann-La Roche: Amyotrophic Lateral Sclerosis; TRO19622; Trophos
• Additional relevant MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Riluzole

Study Results

Participant Flow

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Period Title: Overall Study
STARTED	259	253
COMPLETED	147	139
NOT COMPLETED	112	114

Baseline Characteristics

Arm/Group Title	Olesoxime	Placebo Comparator	Total
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid	Total of all reporting groups
Overall Participants	259	253	512
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (11.2)	55.7 (11.2)	56.5 (11.2)
Sex: Female, Male (Count of Participants)
Female	92 35.5%	89 35.2%	181 35.4%
Male	167 64.5%	164 64.8%	331 64.6%
Region of Enrollment (Count of Participants)
France	113 43.6%	108 42.7%	221 43.2%
Spain	33 12.7%	34 13.4%	67 13.1%
Belgium	13 5%	12 4.7%	25 4.9%
Germany	73 28.2%	74 29.2%	147 28.7%
United Kingdom	27 10.4%	25 9.9%	52 10.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival Rate at 18 Months
Description	Overall survival was defined from the date of randomization until the date of death (event) or last known alive date (censored). If the death date was after 18 months, the participant was censored at 18 months (548 days). Participants still alive at or after 18 months were censored at 18 months/ 548 days. All data over the 18-month follow-up period after randomization, and participant survival status at the 18-month follow-up visit for participants who withdrew prematurely from the study for reasons other than death were included.
Time Frame	From the date of randomization until the date of death or last follow-up censored at 18 months (548 days)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Number (95% Confidence Interval) [percentage of partcipants]	67.5	69.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olesoxime, Placebo Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Stratified Log-Rank Test
	Comments

2. Secondary Outcome

Title	Percentage of Participants With Failure Over 18 Months
Description	Time to failure was defined as the time from randomization to the time of the first event to consider (Tracheostomy, invasive ventilation [IV] or non invasive ventilation [NIV])
Time Frame	From randomization to the time of the first event to consider at 18 months (548 days)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Number (95% Confidence Interval) [percentage of participants]	67.1 25.9%	65.5 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olesoxime, Placebo Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Stratified Log-Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olesoxime, Placebo Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Non-stratified Log-Rank Test
	Comments

3. Secondary Outcome

Title	Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)
Description	The ALSFRS-R is an ordinal rating scale (0 through 4) used to determine the ALS participant's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score from four sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). Total scores range from 0 (most impaired) to 48 (normal ability).
Time Frame	Inclusion, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status. Number analyzed indicates number of participants who were evaluated for the specified time points.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Inclusion	39.1 (4.78)	38.2 (5.25)
Month 1	38.2 (5.46)	37.2 (5.59)
Month 2	37.6 (5.64)	36.7 (6.02)
Month 3	36.4 (6.29)	35.3 (6.62)
Month 6	34.3 (7.11)	33.1 (7.62)
Month 9	32.7 (7.72)	30.4 (8.23)
Month 12	30.5 (8.34)	28.8 (8.47)
Month 15	28.6 (8.56)	27.6 (8.92)
Month 18	27.0 (9.38)	26.3 (9.13)

4. Secondary Outcome

Title	Percentage of Participants With a Global ALS FRS-R Score of <30 or Death
Description	Percentage of participants with a global ALS FRS-R score of < 30 or death was estimated using the Kaplan-Meier method in the ITT, with a two-tailed log-rank, both stratified by site of onset (bulbar or spinal) and non-stratified. The ALSFRS-R is an ordinal rating scale (0 through 4) used to determine the ALS participant's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score from four sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). Total scores range from 0 (most impaired) to 48 (normal ability).
Time Frame	Month 18 (548 days)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Number (95% Confidence Interval) [percentage of participants]	28.2 10.9%	24.9 9.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olesoxime, Placebo Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Stratified Log-Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olesoxime, Placebo Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Non-stratified Log-Rank Test
	Comments

5. Secondary Outcome

Title	Slow Vital Capacity (SVC) Percent Predicted
Description	SVC as a percent of the predicted value was evaluated and reported.
Time Frame	Baseline, Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status. Number analyzed indicates number of participants who were evaluated at specified time points.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Baseline	93.1 (14.6)	93.1 (15.4)
Month 1	89.7 (17.8)	89.7 (17.6)
Month 3	84.8 (20.4)	85.7 (19.7)
Month 6	80.7 (22.9)	80.5 (22.5)
Month 9	77.9 (24.3)	75.5 (24.7)
Month 12	74.5 (25.4)	71.3 (29.0)
Month 15	70.5 (28.8)	71.4 (27.1)
Month 18	69.0 (27.6)	67.1 (25.5)

6. Secondary Outcome

Title	Percentage of Participants With SVC Percent Predicted <70% or Had Died Over 18 Months
Time Frame	Month 18 (548 days)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status. Number analyzed indicates number of participants who were evaluated for specified analysis.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Number (95% Confidence Interval) [percentage of participants]	28.9 11.2%	31.9 12.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olesoxime, Placebo Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Stratified Log-Rank Test
	Comments

7. Secondary Outcome

Title	Global Score of Manual Muscle Testing (MMT) of 34 Muscle Groups
Description	MMT score involved the examination of 30 items. These 30 items are scored from 0 (no trace of contraction) to 5 (normal power at first try). The global score is the sum of the item scores and can range from 0 to 150. Higher score indicates some power.
Time Frame	Inclusion, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status. Number analyzed indicates number of participants who were evaluated for the specified time points.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Inclusion	128 (18.0)	126 (18.8)
Month 3	121 (22.8)	120 (22.0)
Month 6	117 (24.4)	114 (24.6)
Month 9	112 (27.1)	109 (27.1)
Month 12	106 (29.7)	103 (29.6)
Month 15	101 (32.0)	99.2 (31.2)
Month 18	95.2 (33.7)	91.8 (34.7)

8. Secondary Outcome

Title	The Single-Item Mc Gill Quality of Life Scale
Description	The single-item McGill quality of life scale evaluated the following question "Considering all parts of my life - physical, emotional, social, spiritual, and financial - over the past two (2) days, the quality of my life has been…"as a score of 1 to 10 on a visual analog scale where 0 is very bad and 10 is excellent.
Time Frame	Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of study medication administration and eligibility status. Number analyzed indicates number of participants who were evaluated for the specified time points.

Arm/Group Title	Olesoxime	Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.	2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
Measure Participants	259	253
Inclusion	6.51 (1.65)	6.47 (1.65)
Month 1	6.17 (1.73)	6.27 (1.78)
Month 3	5.83 (1.98)	5.75 (1.89)
Month 6	5.55 (2.12)	5.50 (2.00)
Month 9	5.30 (2.14)	5.25 (2.00)
Month 12	4.97 (2.11)	5.10 (2.02)
Month 15	4.96 (2.26)	4.90 (2.13)
Month 18	4.77 (2.29)	5.01 (2.16)

Adverse Events

Time Frame	Safety was assessed during the 18-months study duration.
Adverse Event Reporting Description	Clinical and biological safety of TRO19622 co-administered with riluzole were assessed at each visit.
Arm/Group Title	Olesoxime		Placebo Comparator
Arm/Group Description	2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Olesoxime: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid. Riluzole: Riluzole given as add-on therapy 50mg bid.		2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Placebo Comparator: 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid Riluzole: Riluzole given as add-on therapy 50mg bid
All Cause Mortality
	Olesoxime		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/259 (30.5%)		80/253 (31.6%)
Serious Adverse Events
	Olesoxime		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/259 (26.3%)		65/253 (25.7%)
Blood and lymphatic system disorders
Haemolytic anaemia	1/259 (0.4%)		0/253 (0%)
Cardiac disorders
Myocardial infarction	0/259 (0%)		2/253 (0.8%)
Atrial fibrillation	1/259 (0.4%)		0/253 (0%)
Atrial flutter	0/259 (0%)		1/253 (0.4%)
Cardiac arrest	1/259 (0.4%)		0/253 (0%)
Cardio-respiratory arrest	0/259 (0%)		1/253 (0.4%)
Sinus tachycardia	1/259 (0.4%)		0/253 (0%)
Ear and labyrinth disorders
Vertigo	1/259 (0.4%)		1/253 (0.4%)
Gastrointestinal disorders
Dysphagia	4/259 (1.5%)		2/253 (0.8%)
Acute abdomen	1/259 (0.4%)		0/253 (0%)
Constipation	0/259 (0%)		1/253 (0.4%)
Faecaloma	0/259 (0%)		1/253 (0.4%)
Gastric ulcer	0/259 (0%)		1/253 (0.4%)
Impaired gastric emptying	1/259 (0.4%)		0/253 (0%)
Nausea	1/259 (0.4%)		0/253 (0%)
Pneumoperitoneum	0/259 (0%)		1/253 (0.4%)
Vomiting	1/259 (0.4%)		0/253 (0%)
General disorders
Application site inflammation	1/259 (0.4%)		0/253 (0%)
Application site pain	1/259 (0.4%)		0/253 (0%)
Death	0/259 (0%)		1/253 (0.4%)
Fatigue	1/259 (0.4%)		0/253 (0%)
General physical health deterioration	0/259 (0%)		1/253 (0.4%)
Pain	1/259 (0.4%)		0/253 (0%)
Sudden death	0/259 (0%)		1/253 (0.4%)
Hepatobiliary disorders
Alcoholic liver disease	0/259 (0%)		1/253 (0.4%)
Infections and infestations
Pneumonia	1/259 (0.4%)		5/253 (2%)
Lobar pneumonia	1/259 (0.4%)		2/253 (0.8%)
Lower respiratory tract infection	0/259 (0%)		3/253 (1.2%)
Lung infection	2/259 (0.8%)		1/253 (0.4%)
Respiratory tract infection	0/259 (0%)		2/253 (0.8%)
Bronchopneumonia	0/259 (0%)		1/253 (0.4%)
Cellulitis	0/259 (0%)		1/253 (0.4%)
Gastroenteritis	0/259 (0%)		1/253 (0.4%)
Gastrointestinal fungal infection	1/259 (0.4%)		0/253 (0%)
Parotitis	0/259 (0%)		1/253 (0.4%)
Post procedural infection	1/259 (0.4%)		0/253 (0%)
Sepsis	0/259 (0%)		1/253 (0.4%)
Injury, poisoning and procedural complications
Fall	0/259 (0%)		2/253 (0.8%)
Chest injury	1/259 (0.4%)		0/253 (0%)
Craniocerebral injury	0/259 (0%)		1/253 (0.4%)
Device breakage	1/259 (0.4%)		0/253 (0%)
Face injury	0/259 (0%)		1/253 (0.4%)
Femoral neck fracture	1/259 (0.4%)		0/253 (0%)
Femur fracture	0/259 (0%)		1/253 (0.4%)
Foot fracture	1/259 (0.4%)		0/253 (0%)
Head injury	1/259 (0.4%)		0/253 (0%)
Joint sprain	0/259 (0%)		1/253 (0.4%)
Lumbar vertebral fracture	0/259 (0%)		1/253 (0.4%)
Poisoning deliberate	1/259 (0.4%)		0/253 (0%)
Rib fracture	1/259 (0.4%)		0/253 (0%)
Traumatic brain injury	1/259 (0.4%)		0/253 (0%)
Traumatic intracranial haemorrhage	1/259 (0.4%)		0/253 (0%)
Investigations
Alanine aminotransferase increased	1/259 (0.4%)		0/253 (0%)
Aspartate aminotransferase increased	1/259 (0.4%)		0/253 (0%)
Gamma-glutamyltransferase increased	1/259 (0.4%)		0/253 (0%)
Hepatic enzyme increased	1/259 (0.4%)		0/253 (0%)
Troponin increased	1/259 (0.4%)		0/253 (0%)
Metabolism and nutrition disorders
Dehydration	2/259 (0.8%)		1/253 (0.4%)
Malnutrition	2/259 (0.8%)		0/253 (0%)
Hypokalaemia	1/259 (0.4%)		0/253 (0%)
Hyponatraemia	1/259 (0.4%)		0/253 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/259 (0%)		1/253 (0.4%)
Pain in extremity	1/259 (0.4%)		0/253 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma	0/259 (0%)		1/253 (0.4%)
Squamous cell carcinoma	0/259 (0%)		1/253 (0.4%)
Tongue neoplasm malignant stage unspecified	1/259 (0.4%)		0/253 (0%)
Uterine leiomyoma	0/259 (0%)		1/253 (0.4%)
Nervous system disorders
Transient ischaemic attack	0/259 (0%)		2/253 (0.8%)
Aphasia	0/259 (0%)		1/253 (0.4%)
Areflexia	0/259 (0%)		1/253 (0.4%)
Cerebral haematoma	1/259 (0.4%)		0/253 (0%)
Cerebrovascular accident	0/259 (0%)		1/253 (0.4%)
Dizziness	0/259 (0%)		1/253 (0.4%)
Embolic stroke	0/259 (0%)		1/253 (0.4%)
Hypercapnic encephalopathy	1/259 (0.4%)		0/253 (0%)
Meningorrhagia	1/259 (0.4%)		0/253 (0%)
Psychiatric disorders
Anxiety	3/259 (1.2%)		0/253 (0%)
Depression	1/259 (0.4%)		0/253 (0%)
Completed suicide	0/259 (0%)		1/253 (0.4%)
Sleep disorder	0/259 (0%)		1/253 (0.4%)
Renal and urinary disorders
Urinary retention	1/259 (0.4%)		2/253 (0.8%)
Renal colic	1/259 (0.4%)		0/253 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	14/259 (5.4%)		8/253 (3.2%)
Pulmonary embolism	8/259 (3.1%)		7/253 (2.8%)
Dyspnoea	5/259 (1.9%)		6/253 (2.4%)
Pneumonia aspiration	3/259 (1.2%)		5/253 (2%)
Lung disorder	4/259 (1.5%)		1/253 (0.4%)
Acute respiratory failure	2/259 (0.8%)		0/253 (0%)
Atelectasis	1/259 (0.4%)		1/253 (0.4%)
Bronchial obstruction	0/259 (0%)		2/253 (0.8%)
Choking	1/259 (0.4%)		1/253 (0.4%)
Increased bronchial secretion	0/259 (0%)		2/253 (0.8%)
Respiratory arrest	1/259 (0.4%)		1/253 (0.4%)
Bronchial secretion retention	1/259 (0.4%)		0/253 (0%)
Bronchospasm	0/259 (0%)		1/253 (0.4%)
Cough	0/259 (0%)		1/253 (0.4%)
Haemoptysis	0/259 (0%)		1/253 (0.4%)
Haemothorax	1/259 (0.4%)		0/253 (0%)
Hypoventilation	0/259 (0%)		1/253 (0.4%)
Nocturnal dyspnoea	1/259 (0.4%)		0/253 (0%)
Respiratory tract congestion	0/259 (0%)		1/253 (0.4%)
Surgical and medical procedures
Mechanical ventilation	2/259 (0.8%)		0/253 (0%)
Hysterectomy	0/259 (0%)		1/253 (0.4%)
Vascular disorders
Deep vein thrombosis	3/259 (1.2%)		2/253 (0.8%)
Aortic dissection	0/259 (0%)		1/253 (0.4%)
Circulatory collapse	1/259 (0.4%)		0/253 (0%)
Embolism	0/259 (0%)		1/253 (0.4%)
Pelvic venous thrombosis	1/259 (0.4%)		0/253 (0%)
Phlebitis	0/259 (0%)		1/253 (0.4%)
Thrombophlebitis	1/259 (0.4%)		0/253 (0%)
Venous thrombosis limb	0/259 (0%)		1/253 (0.4%)
Other (Not Including Serious) Adverse Events
	Olesoxime		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	98/259 (37.8%)		101/253 (39.9%)
Gastrointestinal disorders
Diarrhoea	27/259 (10.4%)		15/253 (5.9%)
Nausea	15/259 (5.8%)		16/253 (6.3%)
Infections and infestations
Bronchitis	10/259 (3.9%)		15/253 (5.9%)
Nasopharyngitis	22/259 (8.5%)		36/253 (14.2%)
Injury, poisoning and procedural complications
Fall	26/259 (10%)		19/253 (7.5%)
Nervous system disorders
Headache	19/259 (7.3%)		18/253 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	7/259 (2.7%)		15/253 (5.9%)
Vascular disorders
Hypertension	7/259 (2.7%)		13/253 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only 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 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.