A Randomised, Cross-over Study to Evaluate Efficacy and Tolerability of FLX-787 in Patients with Multiple Sclerosis spasticity and spasms/cramps

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12616000714482
• Date of registration: 30/05/2016
• Prospective Registration: Yes
• Primary sponsor: Flex Pharma, Inc
• 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
• Date of first enrolment: 02/06/2016
• Target sample size: 80
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12616000714482.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Crossover;Type of endpoint: Safety/efficacy;
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Dr Tina Soulis

• Name: Ms Laura Rosen

Key inclusion & exclusion criteria

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
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.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Spasticity & cramps in patients with MS;
Spasticity & cramps in patients with MS

Neurological - Neurodegenerative diseases

Intervention(s)

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 du

Primary Outcome(s)

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
[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)]

Numerical Rating Scale (NRS);
a patient self assessment, measuring muscle spasticity on a 10 point scale [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), ]

Tardieu Scale (TS);
measures muscle response to passive movement at set velocities [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)]

Secondary Outcome(s)

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[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), ]

Timed 25-Foot Walk; measures patients quantitative mobility and leg function [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)]

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.[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), ]

Barthel Activities of Dailey living, measures performance in activities of daily living [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)]

Clinical Global Impression; measures global rating of illness severity, improvement and response to treatment[Day 29 (Visit 3, Day 14 of Run-in Period 1) & Day 64 (Visit 6, Day 14 of Cross-over Period 3)]

Insomnia Severity Index Sleep Survey; for the evaluation of insomnia[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 ID(s)

Nil

Source(s) of Monetary Support

Flex Pharma, Inc

Secondary Sponsor(s)

Neuroscience Trials Australia

Ethics review

Status: Approved
Approval date:
Contact:

Melbourne Health Human Research Ethics Committee