Safety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Therapy in Participants With Spasticity Due to Multiple Sclerosis

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).

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.

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).