INTERVENTIONALTERMINATEDNCT04203498

A Double-blind, Randomized, Placebo-controlled, Parallel-group Trial of the Efficacy and Safety of Nabiximols Oromucosal Spray as Add-on Therapy in Patients With Spasticity Due to Multiple Sclerosis

This trial is being conducted to demonstrate the efficacy of nabiximols, compared with placebo, when added to standard of care, in the treatment of muscle spasms associated with multiple sclerosis (MS).

Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2024-05-08

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: 139 (ACTUAL)
Start date: 2020-10-01
Sponsor: Jazz Pharmaceuticals
Design: RANDOMIZED · PARALLEL · TREATMENT
Locations: 37
Results record: Present in registry snapshot

This multicenter, double-blind, placebo-controlled trial includes a 28-day Baseline period, a 12-week treatment period (comprising a 2-week titration phase and a 10-week maintenance phase), and 2-week follow-up period. Eligible participants will enter the 28-day baseline period. During baseline, participants will maintain their optimized oral MS antispasticity medication regimen and record spasm count using an electronic daily diary. At screening (Day 1), eligible participants will be randomized to either 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 may leave a gap between sprays of approximately 15 minutes. 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. Daily spasm count, the participant's symptom experiences, clinician's assessment of spasticity, functional outcomes, health-related quality of life, changes in mood, safety, tolerability, and pharmacokinetics will be evaluated during the treatment period. Participants who complete the trial will participate for a total of approximately 18 weeks (127 days), including the 28-day baseline period. Participants will have a maximum duration of 85 (±7) days on IMP treatment.

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

Nabiximols is a complex botanical medicine formulated from extracts of the cannabis plant that contains the principal cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and also contains minor constituents, including other cannabinoid and non-cannabinoid plant components, such as terpenes, sterols, and triglycerides.Nabiximols will be self-administered by participants as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks.

GW-1000-02 · Sativex

DRUG

Placebo

Placebo to match nabiximols will be presented as an oromucosal spray containing the excipients ethanol and propylene glycol (50% v/v) with colorings and flavored with peppermint oil (0.05% v/v). Each spray will deliver 100 microliters (μL) containing no active ingredients. Placebo will be self-administered by participants as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks.

Source-reported results

Results posted to the registry

15 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: 14
Statistical analyses: 1
Adverse-event terms: 13

PRIMARYChange in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period

Time frame: Baseline to Week 12
Measure: LEAST_SQUARES_MEAN · daily spasm count
Reporting status: POSTED

The change in the average daily spasm count was assessed compared to the baseline period.

Population: Average daily spasm count was assessed in participants with available data in the Full Analysis Set defined as all patients from the Safety Analysis Set who signed the informed consent and are randomized by interactive response technology..

Group	N	Value	Spread / interval
Nabiximols	67	-2.23	0.412
Placebo	70	-1.62	0.394
Nabiximols	67	-3.42	0.607
Placebo	70	-2.62	0.583
Nabiximols	67	-3.84	0.689
Placebo	70	-3.11	0.659

Statistical analyses

Nabiximols vs PlaceboLinear mixed model repeated measuresDifference in least squares means: -0.73p-value: =0.426395% CI · -2.54 · 1.08

SECONDARYChange in Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score

Eligibility

Population and criteria

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

Inclusion criteria

Criteria at screening: 1. Participant is male or female aged 18 years or above. 2. Participant has had a diagnosis with any disease subtype of multiple sclerosis (MS), by revised 2017 McDonald criteria, for at least 12 months prior to screening and is expected to remain stable for the duration of the trial. 3. Participant has had treatment with at least 1 optimized oral antispasticity therapy prior to Visit 1 that must include either oral baclofen or oral tizanidine (monotherapy or combination therapy). 4. Participant is currently receiving optimized treatment with at least 1 oral antispasticity medication (baclofen, tizanidine, and/or dantrolene) and has been stable for at least 30 days prior to screening. 5. If the participant is currently receiving an approved MS disease-modifying therapy, it must be at a stable dose for at least 3 months prior to screening and is expected to remain stable for the duration of the trial.

Exclusion criteria

1. Participant has any concomitant disease or disorder that has spasticity-like symptoms or that may influence the participant's level of spasticity. 2. Participant has had a relapse of MS within the 60 days prior to screening (Visit 1). 3. Participant is currently using or has used cannabis or a cannabinoid-derived product for medicinal or recreational use (within 30 days of screening) and is unwilling to abstain for the duration of the trial. 4. Participant is currently using botulinum toxin injection for the relief of spasticity (within 6 months of screening) and is unwilling to abstain for the duration of the trial. 5. Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP. 6. Participant is male and fertile unless willing to ensure that he uses male contraception or remains sexually abstinent during the trial and for 3 months thereafter. 7. Participant is female and of childbearing potential unless willing to ensure that she uses a highly effective method of birth control during the trial and for 3 months thereafter. 8. Participant is female and pregnant, lactating, or planning pregnancy during the course of the trial or within 3 months thereafter. 9. Participant has received an IMP within the 30 days prior to screening. 10. Participant has a history of severe psychiatric disorder that may be exacerbated by the use of a cannabinoid-containing product. 11. Participant has any known or suspected history of alcohol or substance abuse (including opiate abuse) or dependence within 1 year prior to screening. 12. Participant is currently taking drugs that are solely metabolized by UGT1A9 and UGT2B7. 13. Participant is currently taking strong currently taking strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital, St John's Wort).

primary outcomes

primary measures

Change in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period

Time frame: Baseline to Week 12

The change in the average daily spasm count was assessed compared to the baseline period.

secondary outcomes

secondary measures

Change in Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score

Time frame: Week 8 and Week 12

The MSSS-88 is a self-reported measure of the impact of spasticity (muscle stiffness and spasms) in MS. This 88-item scale captures the patient experience and impact of spasticity, including muscle stiffness, pain and discomfort, muscle spasms, effect on daily activities, ability to walk, body movement, patient feelings, and social functioning. Responses to individual questions can range from "1 - not at all bothered" to "4 - extremely bothered", ranging from 88 to 352 total score. Scores are summed and higher scores indicate poor clinical outcome. Least square means are being reported, with greater negative values indicating better outcome.

Number of Patients Reporting Any Treatment-emergent Adverse Events

Time frame: From date of first dose of IMP up to 30 days after last dose, up to approximately 16 weeks

A TEAE is an adverse event that started, or worsened in severity or seriousness, following the first dose of the investigational medicinal product.