Trial to Evaluate the Effect of Nabiximols Oromucosal Spray on Clinical Measures of Spasticity in Participants With Multiple Sclerosis

NCT04657666 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: GWSP190662019-002625-29
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 16

Brief Summary

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.

Conditions

Spasticity in Participants With Multiple Sclerosis

Keywords

spasticity; multiple sclerosis; nabiximols; adjunctive therapy; velocity-dependent muscle tone

Outcome Measures

Primary Outcomes (1)

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

  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.

  Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Secondary Outcomes (19)

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

  Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

• Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs)

  Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

• Change From Baseline in Blood Pressure

  Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

• Change From Baseline in Heart Rate

  Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

• Change From Baseline in Weight

  Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Study Arms (2)

Nabiximols

EXPERIMENTAL

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. Each spray delivers 100 microliters (μL) of nabiximols. 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.

Drug: Nabiximols

Placebo

PLACEBO COMPARATOR

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 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.

Drug: Placebo

Interventions

Nabiximols DRUG

oromucosal spray

Also known as: GW-1000-02, Sativex

Nabiximols

Placebo DRUG

oromucosal spray

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify 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 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
• 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 or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal product (IMP)
• 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 (e.g., intrauterine device/hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence) during the trial and for 3 months thereafter. Participants using combined hormonal methods or a progestogen-only pill or injection or implant should use an additional barrier method such as a male 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 history of suicidal behavior in the 5 years prior to Visit 1 or a score of 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the month prior to Visit 1

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (16)

Clinical Trial Site

Choceň, 565 01, Czechia

Location

Clinical Trial Site 2

Poznan, Greater Poland Voivodeship, 61-853, Poland

Location

Clinical Trial Site 1

Poznan, Greater Poland Voivodeship, 62-064, Poland

Location

Clinical Trial Site

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163, Poland

Location

Clinical Trial Site 1

Krakow, Lesser Poland Voivodeship, 30-539, Poland

Location

Clinical Trial Site

Oświęcim, Lesser Poland Voivodeship, 32-600, Poland

Location

Clinical Trial Site 2

Warsaw, Masovian Voivodeship, 01-211, Poland

Location

Clinical Trial Site 1

Warsaw, Masovian Voivodeship, 01-868, Poland

Location

Clinical Trial Site

Gdansk, Pomeranian Voivodeship, 80-803, Poland

Location

Clinical Trial Site

Chorzów, Silesian Voivodeship, 41-500, Poland

Location

Clinical Trial Site 3

Katowice, Silesian Voivodeship, 40-123, Poland

Location

Clinical Trial Site 1

Katowice, Silesian Voivodeship, 40-571, Poland

Location

Clinical Trial Site 2

Katowice, Silesian Voivodeship, 40-684, Poland

Location

Clinical Trial Site

Krakow, 30-149, Poland

Location

Clinical Trial Site

Zabrze, 41-800, Poland

Location

Clinical Trial Site

Kielce, Świętokrzyskie Voivodeship, 25-726, Poland

Location

Related Publications (1)

• Bethoux FA, Farrell R, Checketts D, Sahr N, Berwaerts J, Alexander JK, Skobieranda F. A randomized, double-blind, placebo-controlled trial to evaluate the effect of nabiximols oromucosal spray on clinical measures of spasticity in patients with multiple sclerosis. Mult Scler Relat Disord. 2024 Sep;89:105740. doi: 10.1016/j.msard.2024.105740. Epub 2024 Jun 20.

  PMID: 39106541 DERIVED

MeSH Terms

Conditions

Muscle Spasticity; Multiple Sclerosis

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-832-3750

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: December 8, 2020
• Study Start: December 21, 2020
• Primary Completion: May 4, 2022
• Study Completion: May 10, 2022
• Last Updated: July 20, 2023
• Results First Posted: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); PL (15)