INTERVENTIONALCOMPLETEDNCT04657666

A Randomized, Double-blind, Placebo-controlled, 2-way Crossover Trial to Evaluate the Effect of Nabiximols Oromucosal Spray on Clinical Measures of Spasticity in Patients With Multiple Sclerosis

This study will be conducted 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 (Modified Ashworth Scale Lower Limb Muscle Tone-6 \[MAS LLMT-6\]) in participants with multiple sclerosis (MS) who have not achieved adequate relief from spasticity with other antispasticity medications.

Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2023-07-20

What this record can show

Registry results are available

Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.

Registry facts

Study at a glance

Phase: PHASE3
Enrollment: 68 (ACTUAL)
Start date: 2020-12-21
Sponsor: Jazz Pharmaceuticals
Design: RANDOMIZED · CROSSOVER · TREATMENT
Locations: 16
Results record: Present in registry snapshot

Each period of this multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial includes a 7-day Baseline period, a 3-week treatment period (comprising a 2-week titration phase and a 1-week maintenance phase). Eligible participants will enter the 7-day baseline period of each treatment period. During baseline, participants will maintain their optimized oral MS antispasticity medication regimen and record their 11-point NRS spasticity score and spasm count using an electronic daily diary. On Day 1, eligible participants will be randomized to 1 of 2 treatment sequences, each composed of 2 treatment periods, with administration of multiple doses of nabiximols or placebo in a 1:1 ratio. Participants will be advised to titrate the investigational medicinal product (IMP), beginning with 1 spray/day, to an optimized dose or to a maximum of 12 sprays/day over the first 14 days of treatment. Participants should continue at the same dose level achieved at the end of the titration phase ±1 spray divided into a morning dose and an evening dose for the remainder of the treatment period. Lower limb muscle tone, health-related quality of life, safety, tolerability, and pharmacokinetics will be evaluated during the treatment period. Participants who complete the trial will participate for a maximum of 90 days, which consists of a maximum 29-day screening period and a maximum 61-day treatment period (s), including washout between periods, and safety follow-up.

Linked local records

Related local records

Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.

Conditions

Multiple Sclerosis

Cannabinoids and active compounds

No governed compound link was found.

Medicines

SATIVEX

Interventions

What was registered

DRUG

Nabiximols

oromucosal spray

GW-1000-02 · Sativex

DRUG

Placebo

oromucosal spray

Source-reported results

Results posted to the registry

20 outcomes

Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.

Primary outcomes: 1
Secondary outcomes: 19
Statistical analyses: 1
Adverse-event terms: 8

PRIMARYChange From Baseline in Lower Limb Muscle Tone-6 (LLMT-6)

Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Measure: LEAST_SQUARES_MEAN · units on a scale
Reporting status: POSTED

LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS) transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body. Transformed MAS ranges from 0 (no increase in muscle tone) to 5 (affected part rigid in flexion or extension). The combined (treatment period 1 and treatment period 2) least square mean change from baseline in LLMT-6 score is being reported. Negative values indicate an improvement in muscle tone.

Population: LLMT-6 was assessed in the Full Analysis Set.

Group	N	Value	Spread / interval
Nabiximols	68	-0.23	0.07
Placebo	68	-0.26	0.07

Statistical analyses

Nabiximols vs PlaceboMixed Models AnalysisCombined least mean square difference: 0.04p-value: 0.715295% CI · -0.16 · 0.23

SECONDARYChange From Baseline in Lower Limb Muscle Tone-4 (LLMT-4)

Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Measure: LEAST_SQUARES_MEAN · units on a scale

Eligibility

Population and criteria

Sex: ALL
Minimum age: 18 Years
Maximum age: Not reported
Healthy volunteers: Not accepted

Inclusion criteria

Screening (Visit 1)
Has had a diagnosis with any disease subtype of multiple sclerosis (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 a Modified Ashworth Scale (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 participant 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 participant 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 is 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.
For Randomization (Visit 2): Completed at least 5 of 7 days of their electronic diary reporting during the 7 days immediately preceding Visit 2 (Day 1)

Exclusion criteria

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 participant'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 participant's spasticity

primary outcomes