Symptomatic treatment of spasticity in patients with multiple sclerosis (MS) MedDRA version: 20.0 Level: PT Classification code 10028335 Term: Muscle spasticity System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Sativex Oromucosal Spray
Product Name: Sativex Oromucosal Spray
Pharmaceutical Form:
INN or Proposed INN: Tetrahydrocannabinol Botanical Drug Substance (THC BDS)
CAS Number: 1972-08-3
Oth
Sponsors
GW Pharma Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the trial, patients must fulfill ALL of the following criteria: • Male or female, aged 18 years or above. • Willing and able to give informed consent for participation in the trial. • Willing and able (in the investigator’s opinion) to comply with all trial requirements. • Has had a diagnosis with any disease subtype of MS, by revised 2017 McDonald criteria, for at least 12 months prior to Visit 1 and is expected to remain stable for the duration of the trial. • Has an MAS untransformed score of at least 2 in 2 or more of 6 muscle groups (right knee flexors, left knee flexors, right knee extensors, left knee extensors, right plantar flexors, or left plantar flexors) at Visit 1. • Currently receiving optimized treatment with at least 1 oral antispasticity drug (baclofen, tizanidine, and/or dantrolene) that has been stable for at least 30 days prior to Visit 1. Despite optimization, the patient does not have adequate relief of spasticity symptoms, including muscle spasms. Optimization of antispasticity medications is defined as having reached the most efficacious and best tolerated dose according to the relevant local prescribing information. The patient must be willing to maintain the same antispasticity medication and not plan to initiate a new course of physiotherapy for the duration of the trial. • If currently receiving an approved MS disease-modifying therapy, it must be at a stable dose for at least 3 months prior to Visit 1 and be expected to remain stable for the duration of the trial. • If currently receiving dalfampridine or fampridine, it must be at a stable dose for at least 3 months prior to Visit 1 and is expected to remain stable for the duration of the trial. • Willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law. • Willing to allow his or her primary care practitioner (if he or she has one) and/or treating neurologist (if he or she has one) to be notified of participation in the trial, if the primary care practitioner/treating neurologist is different from the investigator. Additional Inclusion Criteria at Randomization (Visit 2) Patients are eligible for randomization in the trial if, in addition to continuing to meet the Screening (Visit 1) inclusion criteria, they also meet the following criterion prior to Visit 2 (Day 1): • Completed at least 5 of 7 days of their electronic diary reporting during the 7 days immediately preceding Visit 2 (Day 1). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: The patient may not enter the trial if: •Has taken nabiximols, cannabis, or a cannabis-derived product for medicinal or recreational purposes in the 30 days prior to Visit 1 and unable to abstain for the duration of the study •Did not tolerate or did not respond adequately to treatment with nabiximols or another cannabis-based medication if exposed at any time before the 30-day period prior to Visit 1 •Any concomitant disease or disorder that has spasticity-like symptoms or that may influence the patient's level of spasticity •Medical history suggests that relapse/remission is likely to occur during the trial, which, in the opinion of the investigator, is expected to influence the pt's spasticity •Has had a relapse of MS within the 60 days prior to Visit 1 •Currently using botulinum toxin injection for the relief of spasticity (within 6 months of Visit 1) and is unwilling to abstain for the duration of the trial. •Currently taking antipsychotic medication •Currently taking benzodiazepines unless doses and dosing regimen have been stable for at least 30 days prior to Visit 1 •Clinically suspected to have a contracture in one of the muscle groups of the lower limbs, preventing assessment with the MAS •Has any known/suspected hypersensitivity to cannabinoids or any of the excipients of the IMP •Has experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months prior to Visit 1 or has a cardiac disorder that would put the patient at risk of a clinically significant arrhythmia or myocardial infarction •Has a diastolic blood pressure of 105 mmHg or systolic blood pressure 150 mmHg (when measured in a sitting position at rest for 5 minutes) or a postural drop in the systolic blood pressure of > 20 mmHg at Visit 1 or Visit 2 •Has clinically significant impaired renal function at Visit 1, as evidenced by an estimated creatinine clearance lower than 50 mL/min •Has moderately impaired hepatic function at Visit 1, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × upper limit of normal (ULN) •Male and fertile (i.e., after puberty unless permanently sterile by bilateral orchiectomy) unless willing to ensure that he uses male contraception (condom or vasectomy) or remains sexually abstinent during the trial and for 3 months thereafter •Female and of childbearing potential (i.e., following menarche and until becoming postmenopausal for = 12 consecutive months unless permanently sterile by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) unless willing to ensure that she uses a highly effective method of birth control during the trial and for 3 months thereafter. Patients using combined hormonal methods or a progestogen-only pill or injection or implant should use an additional barrier method such as a condom or diaphragm during the trial and for 3 months thereafter •Female and pregnant (positive pregnancy test at Visit 1 or Visit 2), lactating, or planning pregnancy during the course of the trial or within 3 months thereafter •Has received an IMP within the 30 days prior to Visit 1 •Has any other clinically significant disease or disorder (including seizure disorder) that, in the opinion of the investigator, may put the patient, other patients, or site staff at risk because of participation in the trial, may influence the interpretation of trial results, or may affect the patient's ability to take part in the trial •Has any abno
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of multiple doses of nabiximols as adjunctive therapy compared with placebo on a clinical measure of velocity-dependent muscle tone in the lower limbs (Lower Limb Muscle Tone-6; LLMT) in patients with MS who have not achieved adequate relief from spasticity with other antispasticity medications;Secondary Objective: • To evaluate the effect of multiple doses of nabiximols as adjunctive therapy compared with placebo on a clinical measure of velocitydependent muscle tone in the lower limbs (Lower Limb Muscle Tone 4; LLMT-4) in patients with multiple sclerosis (MS) who have not achieved adequate relief from spasticity with other antispasticity medications • To evaluate the pharmacokinetic (PK) profile of nabiximols after administration of multiple doses • To evaluate the safety and tolerability of nabiximols after administration of multiple doses Exploratory objectives • To evaluate the effect of nabiximols after administration of multiple doses on walking using the Timed 25-Foot Walk (T25FW) test • To evaluate the effect of nabiximols after administration of multiple doses on the following patient-reported outcomes: - The 11-point Numerical Rating Scale (NRS) spasticity score - Daily spasm count - The MS Spasticity Scale (MSSS-88) total and subdomain scores;Primary end point(s): Change in Lower Limb Muscle Tone-6 (LLMT-6; defined as the average of the 6 individual MAS transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body) from Day 1 predose to Day 21 and from Day 31 predose to Day 51.;Timepoint(s) of evaluation of this end point: Day 1 predose & Day 21 Day 31 predose & Day 51 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Change in Lower Limb Muscle Tone-4 (LLMT-4; defined as the average of the 4 individual MAS transformed scores of knee flexors and knee extensors on both sides of the body) from Day 1 predose to Day 21 and from Day 31 predose to Day 51 Pharmacokinetics: • Plasma concentrations for ?9-tetrahydrocannabinol (THC) and its relevant metabolites (11-hydroxy-?9-tetrahydrocannabinol and 11-carboxy- ?9-tetrahydrocannabinol) and cannabidiol (CBD) and its relevant metabolites (7-hydroxy-cannabidiol and 7-carboxy-cannabidiol) at distinct time points during each treatment period (Visit 2) Safety: • Frequency of treatment-emergent adverse events (TEAEs) • Change from baseline to the last visit of each double-blind treatment period (i.e., Visits 4 and 7) for the following: - Clinical laboratory parameters - Vital signs - Physical examination procedures - 12-lead electrocardiograms (ECGs) - Columbia-Suicide Severity Rating Scale (C-SSRS) Exploratory end points Efficacy: • Difference between treatments in total and subdomain scores of the MSSS-88 at the end of the maintenance-dose phase of each double-blind treatment period • Difference between treatments in average 11-point NRS spasticity score over the last 7 days of each double-blind treatment period • Difference between treatments in average daily spasm count over the last 7 days of each double-blind treatment period • Difference between treatments in the change in Timed 25-Foot Walk (T25FW) test from Day 1 predose to Day 21 and from Day 31 predose to Day 51;Timepoint(s) of evaluation of this end point: Efficacy: Day 1 predose to Day 21, Day 31 predose to Day 51 Pharmacokinetics: Day 1 predose & postdose, Day 15, Day 21, Day 31 predose & postdose, Day 45, Day 51. Safety: all visits Efficacy • MSSS-88: Day 21 & Day 51 • NRS spasticity score: Day 1 predose, Day 15-31 & Day 45-51 • daily spasm count: Day 1 predose, Day 15-31 & Day 45-51 • T25FW: Day 1 predose, Day 21-31 & Day 5 | — |
Countries
Poland, United Kingdom
Contacts
Public ContactRegulatory affairs manager
GW Pharma Limited
Outcome results
None listed