Evaluation of the Effect of Nabiximols Oromucosal Spray on Clinical Measures of Spasticity in Participants With Multiple Sclerosis (RELEASE MSS5)
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|ClinicalTrials.gov Identifier: NCT04984278|
Recruitment Status : Terminated (The study was terminated based on a business decision by the Sponsor.)
First Posted : July 30, 2021
Last Update Posted : December 1, 2022
|Condition or disease||Intervention/treatment||Phase|
|Spasticity With Multiple Sclerosis||Drug: Nabiximols Drug: Placebo||Phase 3|
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 Numerical Rating Scale (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 total of approximately 11 weeks (77 days), including the 7-day baseline period.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||56 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Actual Study Start Date :||August 16, 2021|
|Actual Primary Completion Date :||November 11, 2022|
|Actual Study Completion Date :||November 11, 2022|
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. Study dependent: Each spray delivers 100 microliters (μL) of nabiximols. A pre-determined number of sprays, but no less than 4 sprays, of nabiximols will be self-administered by participants as an oromucosal spray, under supervision of trial staff during 2 study visits to the trial site after they temporarily discontinued treatment with prescribed nabiximols (Sativex) as part of their regular medication.
Placebo Comparator: Placebo
Placebo to match nabiximols is 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 delivers 100 μL containing no active ingredients.
- Change in Lower Limb Muscle Tone-6 (LLMT-6) from Day 1 predose to Day 21 (Treatment Period 1) and from Day 31 predose to Day 51 (Treatment Period 2) [ Time Frame: predose on Days 1 and 31; Days 21 and 51 ]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.
- Change in LLMT-4 from Day 1 predose to Day 21 and from Day 31 predose to Day 51 [ Time Frame: predose on Days 1 and 31; Days 21 and 51 ]LLMT-4 is defined as the average of the 4 individual MAS transformed scores of knee flexors and knee extensors on both sides of the body.
- Number of participants with treatment-emergent adverse events [ Time Frame: up to Day 58 ]
- Number of participants with clinically significant changes in clinical laboratory parameters from Baseline to Day 51 [ Time Frame: Baseline; up to Day 51 ]
- Number of participants with clinically significant changes in vital sign values from Baseline to Day 58 [ Time Frame: Baseline; up to Day 58 ]
- Number of participants with clinically significant changes in physical examination procedures from Baseline to Day 51 [ Time Frame: Baseline; up to Day 51 ]
- Number of participants with clinically significant changes in 12-lead electrocardiogram parameters from Baseline to Day 51 [ Time Frame: Baseline; up to Day 51 ]
- Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Screening (Visit 1) and at each subsequent timepoint with reference to the last assessment (since last visit) [ Time Frame: Screening; up to Day 58 ]
- Plasma concentrations for Δ9-tetrahydrocannabinol (THC) and its relevant metabolites (11-hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-carboxy-Δ9-tetrahydrocannabinol [11-COOH-THC]) [ Time Frame: Day 1: predose; 0-2 and 2-4 hours (hr) postdose (PD). Day 15: 0-2 and 2-4 hr PD. Day 21: predose; 0-1 and 2-3 hr PD. Day 31: predose; 0-2 and 2-4 hr PD. Day 45: 0-2 and 2-4 hr PD. Day 51: predose; 0-1 and 2-3 hr PD ]Days 1, 15, 21, 31, 45, and 51
- Plasma concentrations for cannabidiol (CBD) and its relevant metabolites (7-hydroxy-cannabidiol [7-OH-CBD] and 7-carboxy-cannabidiol [7-COOH-CBD]) [ Time Frame: Day 1: predose; 0-2 and 2-4 hr PD. Day 15: 0-2 and 2-4 hr PD. Day 21: predose; 0-1 and 2-3 hr PD. Day 31: predose; 0-2 and 2-4 hr PD. Day 45: 0-2 and 2-4 hr PD. Day 51: predose; 0-1 and 2-3 hr PD ]Days 1, 15, 21, 31, 45, and 51
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04984278