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Trial registered on ANZCTR


Trial ID
ACTRN12616001060437
Ethics application status
Approved
Date submitted
14/01/2016
Date registered
9/08/2016
Date last updated
16/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A trial to evaluate the effect of FLX-787 ODT on Motor Neuron Disease.
Scientific title
A Randomised, Cross-over Study to Evaluate Efficacy and Tolerability of FLX-787 in Patients with Motor Neuron Disease
Secondary ID [1] 288002 0
Nil
Universal Trial Number (UTN)
Trial acronym
Flex-202
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spasticity & cramps in patients with Motor Neuron Disease 296885 0
Condition category
Condition code
Neurological 297113 297113 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be asked to consume two study products (placebo and active) during the screening visit. Eligible Subjects who can consume the products will enter the study and commence Run-In, a 14 day period.
During the 14 day Run-In period all subjects will complete a daily telephone questionnaire through an IVRS to document information on the previous day's cramps as well as obtain information on Subjects Spacticity through the measurement of the NRS.
Upon completion of the Run-In, Subjects will be randomised to one of two possible sequences (Control - Active or Active - Control). Subjects will be allocated to each sequence in a one to one ratio. Subjects will be instructed to take study product two times a day, morning and evening.. Each Cross-over Period (Periods 1 and 2) is 14 days. There will be a 7-day Wash-out between Period 1 and Period 2

Subjects will be given additional study product to account for a 3 day window and potential spills/contamination.

Each treatment may include a combination of any of the following:
Component of Ginger
Ethanol alcohol (trace amount)
Lactose
Sucrose
Aspartame
Water

Participants will consume a single oral disintegrating tablet twice daily, morning and evening.

Adherence to the intervention will be monitored via product return.

Intervention code [1] 293339 0
Treatment: Drugs
Comparator / control treatment
Inactive oral disintegrating tablet twice daily, morning and evening

Control group
Placebo

Outcomes
Primary outcome [1] 296727 0
Efficacy will be measured by change from baseline by: Modified Ashworth Scale (MAS): measuring muscle tone
Timepoint [1] 296727 0
After Run In 14 day period (Visit 2) and treatment period (Visit 3) and end of study or early termination (Visit 5)
Primary outcome [2] 299074 0
Tardieu Scale (TS): measures muscle response to passive movement at set velocities.
Timepoint [2] 299074 0
After Run In 14 day period (Visit 2) and treatment period (Visit 3) and end of study or early termination (Visit 5)
Primary outcome [3] 299075 0
Insomnia Severity Index (ISI) Survey; for the evaluation of insomnia
Timepoint [3] 299075 0
After Run In 14 day period (Visit 2) and treatment period (Visit 3) and end of study or early termination (Visit 5)
Secondary outcome [1] 319206 0
Safety will be measured by AEs, Laboratory Evaluations and Vital Signs. AEs will be monitored and collected from the time the ICF is signed through the follow up call (7 days post last study product administration). Laboratory evaluations and vital signs will be assessed throughout the study.
Timepoint [1] 319206 0
At screening, Day 29 (Visit 2, Day 14 of Run-in Period), Day 43 (Visit 3, end Cross-over Period 1), Day 50 (Visit 4, Day 7 of Wash out- Period), Day 64 (Visit 5, Day14 of Cross-over Period 2) and Visit 6 (drop out visit),
Secondary outcome [2] 326071 0
ALS Assessment Questionnaire (ALSAQ): assessing areas of importance to patients with ALS/MND.
Timepoint [2] 326071 0
After Run In 14 day period (Visit 2) and treatment period (Visit 3) and end of study or early termination (Visit 5)
Secondary outcome [3] 326072 0
Numerical Rating Scale (NRS) for spasticity; patient reported outcome measure used in the assessment of spasticity.
Timepoint [3] 326072 0
Run in Period (Days 1- 13), Cross-over Period 1 (Days 1- 13) Day; Cross-over Period 2 Days (1-13).
Secondary outcome [4] 326081 0
Patient Global Impression of Change (PGI-C) scale; patient's rating of overall improvement
Timepoint [4] 326081 0
End of Period 1 (Visit 3); End of Period 2 or Early Termination visit (Visit 5)
Secondary outcome [5] 326084 0
Clinical Global Impression (CGI) scale: measures global rating of illness severity, improvement and response to treatment
Timepoint [5] 326084 0
End of Period 1 (Visit 3); End of Period 2 or Early Termination visit (Visit 5)

Eligibility
Key inclusion criteria
1.Diagnosed with Amyotrophic Lateral Sclerosis (ALS) or Progressive Lateral Sclerosis (PLS) for at least 12 months;
2.Subjects must be able to provide written informed consent;
3.Subjects must be able and willing to comply with all study requirements;
4.Subjects must be able to take the study products;
5.Spasticity of at least 3 months duration that is not completely relieved by current therapy;
6.Subjects with an estimated > 60 cramps per month (or > 15 per week); and,
7.All females of childbearing potential will agree to use a medically acceptable method of contraception throughout the duration of the study and have a negative urine pregnancy test at screening.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Subjects with flaccid paralysis;
2.Subjects with significant cognitive impairment, clinical dementia or psychiatric illness;
3.Subjects with a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer disease);
4.Subjects who have a food allergy or intolerance/hypersensitivity to products containing ginger;
5.Subjects with a history of abuse of any street drugs such as marijuana or illicit drugs or alcohol within the past 1 year prior to signing the Informed Consent Form (ICF);
6. Use of any tobacco- or nicotine-containing products within 1 week prior to Screening and throughout the duration of the study;
7.Subjects who participated in an interventional clinical study within 30 days prior to the first administration of study product;
8.Subjects whose other conditions/diseases are unstable and are likely to result in hospitalisation or a change in their medication regimen;
9.Subjects who are pregnant or lactating; and,
10.Subjects who in the opinion of the Investigator are not suitable to participate in this clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Each participant will be assigned a unique identification number. Participants who complete study screening assessments and meet all the eligibility criteria will receive corresponding treatment (control, active) according to the randomization schedule at the end of the run in period.

Allocation was concealed by computer randomization scheme developed to assign the subject with corresponding treatment (control, active).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerized randomisation scheme created by study statistician
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
50 participants will be recruited and will be randomly allocated to receive orally disintegrating tablets in a crossover manner.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The sample size chosen for this study was based upon results from three previous Flex studies and was selected without statistical considerations.
As there are multiple endpoints, it is assumed this sample size will be sufficient to provide initial indication of efficacy for the other endpoints.
The following endpoints will be used in the study:


Worsening of the following from baseline:
Pain and Intensity of Cramps;
Insomnia Severity Index (ISI) Survey;
ALS Assessment Questionnaire (ALSAQ);
Numerical Rating Scale (NRS) for spasticity;
Modified Ashworth Scale (MAS);
Tardieu Scale;
Patient Global Impression of Change (PGIC) scale;
Clinical Global Impression (CGI) scale

Safety Endpoints:
Percentage of Subjects with treatment-emergent AEs;
Change in Vital Sign parameters from Screening; and;
Change in laboratory parameters from Screening

The study is exploratory in nature, The efficacy endpoints will be summarised by Treatment Sequence and Period. A paired Wilcoxon signed rank test will be conducted to test for treatment effect at the 5% level of significance. The following descriptive statistics: arithmetic mean (AM), standard deviations (SD), sample size (N), coefficient of variation (CV), median, minimum and maximum values will be calculated for the continuous efficacy endpoints (primary and exploratory) by treatment and time point.
All data will be summarised based on the safety population and data will be presented by Treatment Group within Treatment Sequence and Treatment Group. The actual treatment received will be presented.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 4797 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment hospital [2] 6419 0
Calvary Health Care Bethlehem Ltd - Caulfield
Recruitment hospital [3] 6420 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 12304 0
2050 - Camperdown
Recruitment postcode(s) [2] 13958 0
3162 - Caulfield
Recruitment postcode(s) [3] 13959 0
4029 - Royal Brisbane Hospital

Funding & Sponsors
Funding source category [1] 292463 0
Commercial sector/Industry
Name [1] 292463 0
Flex Pharma, Inc
Address [1] 292463 0
Prudential Tower
800 Boylston St
24th Floor, Boston MA 02199
Country [1] 292463 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Flex Pharma, Inc
Address
Prudential Tower
800 Boylston St
24th Floor, Boston MA 02199
Country
United States of America
Secondary sponsor category [1] 291162 0
Commercial sector/Industry
Name [1] 291162 0
Neuroscience Trials Australia
Address [1] 291162 0
345 Burgundy St
Heidelberg VIC 3084
Country [1] 291162 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294161 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 294161 0
c/- Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 294161 0
Australia
Date submitted for ethics approval [1] 294161 0
18/01/2016
Approval date [1] 294161 0
16/06/2016
Ethics approval number [1] 294161 0
HREC/16/RPAH/12

Summary
Brief summary
The study aims to evaluate the effects and safety of FLX-787 in patients with Motor Neuron Disease who experience muscle cramps and spasms. We aim to assess the effect of FLX-787 on pain/intensity and insomnia. Active/Placebo ODT is self administered morning and evening.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61830 0
Prof Matthew Kiernan
Address 61830 0
University of Sydney
Brain & Mind Centre
Building F, Level 4
94 Mallett St
Camperdown NSW 2050
Country 61830 0
Australia
Phone 61830 0
+61 2 9114 4250
Fax 61830 0
+61 2 9114 4254
Email 61830 0
matthew.kiernan@sydney.edu.au
Contact person for public queries
Name 61831 0
Dr Tina Soulis
Address 61831 0
Neuroscience Trials Australia
245 Burgundy Street
Heidelberg VIC 3084
Country 61831 0
Australia
Phone 61831 0
+61 3 9035 7158
Fax 61831 0
Email 61831 0
asoulis@unimelb.edu.au
Contact person for scientific queries
Name 61832 0
Ms Laura Rosen
Address 61832 0
FlexPharma Inc.
Prudential Tower
800 Boylston Street, 24th Floor,
Boston MA 02199
Country 61832 0
United States of America
Phone 61832 0
+1 (484) 547 4729
Fax 61832 0
Email 61832 0
lrosen@flex-pharma.com