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Trial registered on ANZCTR


Registration number
ACTRN12616000714482
Ethics application status
Approved
Date submitted
3/02/2016
Date registered
30/05/2016
Date last updated
23/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Cross-over Study to Evaluate Efficacy and Tolerability of FLX-787 in Patients with Multiple Sclerosis spasticity and spasms/cramps
Scientific title
A Randomised, Cross-over Study to Evaluate Efficacy and Tolerability of FLX-787 in Patients with Multiple Sclerosis spasticity and spasms/cramps
Secondary ID [1] 288473 0
Nil
Universal Trial Number (UTN)
Trial acronym
Flex 201
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spasticity & cramps in patients with MS 297509 0
Condition category
Condition code
Neurological 297707 297707 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible Subjects will enter the study and commence the Enrolment Period 1, a 14-day period during which all Subjects will receive capsules, the capsules will be consumed twice daily, one in the morning and once in the evening.
Upon completion of Period 1, Subjects who remain eligible will be randomised to one of two possible treatment sequences (Inactive Control – FLX-787 or FLX-787 – Inactive Control). FLX-787 or Inactive Control are both oral beverages which will be taken twice daily for one of two 14-day Cross-over Periods. Self-administration will take place in the morning approximately within an hour of rising and in the evening approximately 45 minutes before going to bed.
Subjects will be allocated to each treatment sequence in a 1:1 ratio. There will be a 7-14 day Wash-out Period between Period 1 and Period 2. Each Cross-over Period (Periods 2 and 3) is 14 days. There will be a 7-14 day Wash-out Period between Periods 2 and 3.
Assessments will be performed and surveys will be completed at each clinic visit according to the study events flow chart.
In addition to the in-clinic assessments, Subjects will be completing daily telephone surveys through an Interactive Voice Response System (IVRS) to document information on the previous days muscle spasms/cramps (including number of, time, duration, location, and pain level), the level of spasticity according to the NRS and study product compliance.
Subjects will return to the centre for an End of Treatment Visit (or Early Termination Visit if they withdraw before the end of the study).
In addition, a follow-up telephone interview to assess adverse events (AEs) will take place 30 days after the last administration of the study product.
Each clinic visit will have a +3-day visit window after the due date to account for scheduling conflicts/holidays/weekends.
Subjects will be given an additional six (6) doses of study product to allow for continued dosing through the 3-day visit window if needed.
Intervention code [1] 293810 0
Treatment: Drugs
Comparator / control treatment
25ml, inactive beverage consumed orally twice daily, morning and evening
Control group
Placebo

Outcomes
Primary outcome [1] 297239 0
The alternate primary objectives of this study are to assess the effects of FLX-787 in multiple sclerosis (MS) Subjects with spasticity and spasms/cramps as measured by:
Modified Ashworth Scale (MAS); measuring muscle tone
Timepoint [1] 297239 0
At screening, Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2) & Day 64 (Visit 6, Day 14 of Cross-over Period 3)
Primary outcome [2] 297327 0
Tardieu Scale (TS);
measures muscle response to passive movement at set velocities
Timepoint [2] 297327 0
At screening, Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2) & Day 64 (Visit 6, Day 14 of Cross-over Period 3)
Primary outcome [3] 297328 0
Numerical Rating Scale (NRS);
a patient self assessment, measuring muscle spasticity on a 10 point scale
Timepoint [3] 297328 0
At screening, Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2), Day 64 (Visit 6, Day 14 of Cross-over Period 3) and Visit 7 (drop out visit),
Secondary outcome [1] 320431 0
Tolerability 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 (30 days post last study product administration). Laboratory evaluations and vital signs will be assessed throughout the study.
Timepoint [1] 320431 0
At screening, Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2), Day 64 (Visit 6, Day 14 of Cross-over Period 3) and Visit 7 (drop out visit),
Secondary outcome [2] 321699 0
Barthel Activities of Dailey living, measures performance in activities of daily living
Timepoint [2] 321699 0
Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2) & Day 64 (Visit 6, Day 14 of Cross-over Period 3)
Secondary outcome [3] 321700 0
Timed 25-Foot Walk; measures patients quantitative mobility and leg function
Timepoint [3] 321700 0
Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2) & Day 64 (Visit 6, Day 14 of Cross-over Period 3)
Secondary outcome [4] 321702 0
Clinical Global Impression; measures global rating of illness severity, improvement and response to treatment
Timepoint [4] 321702 0
Day 29 (Visit 3, Day 14 of Run-in Period 1) & Day 64 (Visit 6, Day 14 of Cross-over Period 3)
Secondary outcome [5] 321703 0
Quality of Life Questionnaires:
36-Item Short Form Survey; patient-reported survey of patient health. Scoring general health and pain.

Multiple Sclerosis Spasticity Scale; measure the impact of spasticity in multiple sclerosis
Timepoint [5] 321703 0
Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2), Day 64 (Visit 6, Day 14 of Cross-over Period 3) and Visit 7 (drop out visit),
Secondary outcome [6] 321704 0
Insomnia Severity Index Sleep Survey; for the evaluation of insomnia
Timepoint [6] 321704 0
Day 15 (Visit 2, day -1 Run-in Period 1), Day 29 (Visit 3, Day 14 of Run-in Period 1), Day 43 (Visit 4, end Cross-over Period 2), Day 64 (Visit 6, Day 14 of Cross-over Period 3) and Visit 7 (drop out visit),

Eligibility
Key inclusion criteria
1. Diagnosed with any sub-type of MS for at least 6 months except for Subjects with acute relapse within 4 weeks of Screening;
2. Spasticity of at least 3 months duration that is not completely relieved by current therapy;
3. Naïve Subjects or Subjects who are on antispasmodic medication for at least 30 days;
4. Males will agree to use a medically acceptable method of contraception and will refrain from sperm donation throughout the duration of the study; and,
5. All females, regardless 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.
6. Subjects who have =6 cramps during Period 1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any concomitant disease or disorder that has symptoms of spasticity, or that may influence the Subject’s level of spasticity;
2. Subjects who are suffering from an acute relapse or have suffered an acute relapse within 4 weeks of Screening;
3. Expanded Disability Status Scale equal or greater than 7;
4. Significant cardiac, renal or hepatic impairment;
5. Started or altered the dose levels of any of the following agents: skeletal muscle relaxants (i.e. Flexerol), anti-spasm drugs or anti-convulsants within 6 weeks prior to the first administration of study product;
6. Subjects currently taking over the counter medications or dietary supplements to treat cramps or spasms (including topical patches);
7. Subjects using strong tranquilizers such as benzodiazepines;
8. Subjects using street drugs such as marijuana;
9. Subjects who have a food allergy or intolerance/hypersensitivity to products containing ginger;
10. Abuse of any illicit drugs or alcohol within the past 1 year prior to the Screening and throughout the duration of the study;
11. Subjects with diabetes;
12. Subjects with Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg) and/or Hepatitis C Virus (HCV);
13. Participation in an interventional clinical study within 30 days prior to the first administration of study product;
14. Subjects who are unlikely/unwilling to refrain from eating spicy foods or beverages throughout the study (for example, cinnamon, ginger, chilli peppers, hot sauces, mustard, pickles);
15. Subjects who have medical fragility, e.g., a Body Mass Index (BMI) falling below the lower threshold of the healthy adult reference range, or a history of recurrent hospital readmissions;
16. Subjects whose other conditions/diseases are unstable and are likely to result in changes in their concomitant medication (to avoid doubt this includes the addition of new medications or change of dose in an existing medication.);
17. Subjects who are unable to complete the T25-FW; and,
18. 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)
central randomization by computer generated list held by unblinded pharmacist
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
80 participants will be recruited and will be randomly allocated to receive beverage in a crossover manner.

Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2016
Actual
2/06/2016
Date of last participant enrolment
Anticipated
1/03/2017
Actual
17/11/2017
Date of last data collection
Anticipated
Actual
29/01/2018
Sample size
Target
80
Accrual to date
Final
73
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 5221 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment hospital [2] 5222 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 5223 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [4] 5853 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 10962 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [6] 10963 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [7] 10964 0
Griffith University Clinical Trials Unit - Southport
Recruitment hospital [8] 10965 0
Calvary Wakefield Hospital - Adelaide
Recruitment postcode(s) [1] 12693 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [2] 12694 0
3084 - Heidelberg
Recruitment postcode(s) [3] 13293 0
2305 - New Lambton Heights
Recruitment postcode(s) [4] 13294 0
2050 - Camperdown
Recruitment postcode(s) [5] 22750 0
2065 - St Leonards
Recruitment postcode(s) [6] 22751 0
3168 - Clayton
Recruitment postcode(s) [7] 22752 0
4215 - Southport
Recruitment postcode(s) [8] 22753 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 292816 0
Commercial sector/Industry
Name [1] 292816 0
Flex Pharma, Inc
Country [1] 292816 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] 291557 0
Commercial sector/Industry
Name [1] 291557 0
Neuroscience Trials Australia
Address [1] 291557 0
345 Burgundy St.
Heidelberg Victoria 3084
Country [1] 291557 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294322 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 294322 0
Ethics committee country [1] 294322 0
Australia
Date submitted for ethics approval [1] 294322 0
21/10/2015
Approval date [1] 294322 0
16/12/2015
Ethics approval number [1] 294322 0
HREC/15/MH/332

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63290 0
Dr Anneke Van der Walt
Address 63290 0
Royal Melbourne Hospital
Level 4, Main Building
300 Grattan St.
Parkville VIC 3050
Country 63290 0
Australia
Phone 63290 0
+61 3 93429092
Fax 63290 0
+61 3 93495997
Email 63290 0
[email protected]
Contact person for public queries
Name 63291 0
Tina Soulis
Address 63291 0
Neuroscience Trials Australia
245 Burgundy St
Heidelberg VIC 3084
Country 63291 0
Australia
Phone 63291 0
+61 3 90357158
Fax 63291 0
Email 63291 0
[email protected]
Contact person for scientific queries
Name 63292 0
Laura Rosen
Address 63292 0
FlexPharma Inc
Prudential Tower
800 Boylston St, 24th Floor
Boston MA 02199
Country 63292 0
United States of America
Phone 63292 0
+1 484 5474729
Fax 63292 0
Email 63292 0
[email protected]

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No Supporting Document Provided



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