Spasticity in Participants With Multiple SclerosisPhase 3RELEASE MSS1NCT04657666
Trial to Evaluate the Effect of Nabiximols Oromucosal Spray on Clinical Measures of Spasticity in Participants With Multiple Sclerosis
A Phase 3 study testing Nabiximols in people with Spasticity in Participants With Multiple Sclerosis, run by Jazz Pharmaceuticals at 16 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Spasticity in Participants With Multiple Sclerosis
- What is being tested?
- Nabiximols
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 16 sitesin 2 countries
- Study dates
- 21 Dec 2020to 10 May 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 22Show fewer
- 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
- Has donated blood during the 3 months prior to Visit 1 and is unwilling to abstain from donation of blood during the trial
- Has been previously randomized into this trial
- Has any known or suspected history of alcohol or substance abuse (including opiate abuse) or dependence within 1 year prior to Visit 1
- Currently using an illicit drug or current nonprescribed use of any prescription drug
- Has a history of psychiatric or neurologic disorder that, in the opinion of the investigator, may interfere with trial participation, data interpretation, or conduct of trial procedures
- Has a history of severe psychiatric disorder that may be exacerbated by the use of a cannabinoid-containing product.
- Has any planned clinical interventions or intends to change any or all medications that may have an effect on spasticity or MS during the trial
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
Poland15 sites
Clinical Trial Site
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163
Clinical Trial Site
Chorzów, Silesian Voivodeship, 41-500
Clinical Trial Site
Gdansk, Pomeranian Voivodeship, 80-803
Clinical Trial Site 3
Katowice, Silesian Voivodeship, 40-123
Clinical Trial Site 1
Katowice, Silesian Voivodeship, 40-571
Clinical Trial Site 2
Katowice, Silesian Voivodeship, 40-684
Clinical Trial Site
Kielce, Świętokrzyskie Voivodeship, 25-726
Clinical Trial Site 1
Krakow, Lesser Poland Voivodeship, 30-539
Clinical Trial Site
Krakow, 30-149
Clinical Trial Site
Oświęcim, Lesser Poland Voivodeship, 32-600
Clinical Trial Site 2
Poznan, Greater Poland Voivodeship, 61-853
Clinical Trial Site 1
Poznan, Greater Poland Voivodeship, 62-064
Clinical Trial Site 2
Warsaw, Masovian Voivodeship, 01-211
Clinical Trial Site 1
Warsaw, Masovian Voivodeship, 01-868
Clinical Trial Site
Zabrze, 41-800
About this study
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
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.
Read the detailed description
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.
- Being tested
- Nabiximols, Placebo
- Keywords
- spasticity, multiple sclerosis, nabiximols, adjunctive therapy, velocity-dependent muscle tone
- Medical subject headings
- Muscle Spasticity, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NabiximolsDrug
Also called GW-1000-02, Sativex
oromucosal spray
PlaceboDrug
oromucosal spray
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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. 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-4 score is being reported. Negative values indicate an improvement in muscle tone.
Measured: 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)
A TEAE is an adverse event that started, or worsened in severity or seriousness, following the first dose of the investigational medicinal product.
Measured: 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
Measured: 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
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Weight
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Body Mass Index
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Clinical Laboratory Test Values
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Erythrocytes
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Hemoglobin
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Hematocrit Ratio
Hematocrit was measured in whole blood samples. The ratio of packed cells to total volume was assessed. Normal ratio ranges from 0.350-0.470 female and 0.400-0.540 male (normal ranges per our central lab), 0.37 (or 37%) to 0.52 (or 52%) in adults. Lower hematocrit ratios indicate worse clinical outcome.
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Erythrocyte Mean Corpuscular Volume
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Electrocardiogram Parameters
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Electrocardiogram Pulse Rate
Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Number of Participants With Suicidal Ideation or Behavior Based on The Columbia Suicide Severity Rating Scale (CSSRS)
The C-SSRS is a short questionnaire that is used to assess suicidal ideation (5 questions) and behavior (5 questions) since last patient visit. The questionnaire is completed by participants answering yes or no to each question.
Measured: Baseline, Day 15, and Day 21
Plasma Concentrations for Δ9-tetrahydrocannabinol (THC)
Plasma concentrations were assessed using blood samples collected at the timepoints specified.
Measured: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Plasma Concentrations for Relevant Metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC), for Δ9-tetrahydrocannabinol (THC)
Plasma concentrations were assessed using blood samples collected at the timepoints specified.
Measured: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Plasma Concentrations for Cannabidiol (CBD)
Plasma concentrations were assessed using blood samples collected at the timepoints specified.
Measured: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Plasma Concentrations for Relevant Metabolites, 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD), for Cannabidiol (CBD)
Plasma concentrations were assessed using blood sample collected at the timepoints specified.
Measured: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start21 Dec 2020
- Primary completion4 May 2022
- Study completion10 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spasticity in Participants With Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04657666
- Sponsor's protocol ID
- GWSP19066
- Other IDs
- 2019-002625-29, 2019
- Acronym
- RELEASE MSS1
- Status last verified
- Jul 2023
- First submitted
- 11 Nov 2020
- Last updated
- 20 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39106541
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04657666
- Acronym / sponsor ID
- RELEASE MSS1 / GWSP19066
- Keywords
- spasticity, multiple sclerosis, nabiximols, adjunctive therapy, velocity-dependent muscle tone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2020 (actual)
- Primary completion
- 4 May 2022 (actual)
- Study completion
- 10 May 2022 (actual)
- First posted
- 8 Dec 2020 (actual)
- Results
- Posted 20 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nabiximols | Experimental | Drug: NabiximolsNabiximols 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NabiximolsAlso: GW-1000-02, Sativexoromucosal spray | Drug | Nabiximols |
| Placebooromucosal spray | Drug | Placebo |
Primary outcome
Change 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)
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.
19 secondary outcomes
Change 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)
Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs)
Time frame: 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
Time frame: 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
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Weight
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Body Mass Index
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Clinical Laboratory Test Values
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Erythrocytes
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Hemoglobin
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Hematocrit Ratio
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Erythrocyte Mean Corpuscular Volume
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Electrocardiogram Parameters
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Change From Baseline in Electrocardiogram Pulse Rate
Time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)
Number of Participants With Suicidal Ideation or Behavior Based on The Columbia Suicide Severity Rating Scale (CSSRS)
Time frame: Baseline, Day 15, and Day 21
Plasma Concentrations for Δ9-tetrahydrocannabinol (THC)
Time frame: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Plasma Concentrations for Relevant Metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC), for Δ9-tetrahydrocannabinol (THC)
Time frame: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Plasma Concentrations for Cannabidiol (CBD)
Time frame: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Plasma Concentrations for Relevant Metabolites, 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD), for Cannabidiol (CBD)
Time frame: Period 1: Day 1: predose,0-2 and 2-4 hours (hr) postdose. Day 15: 0-2 and 2-4 hr postdose. Day 21: predose,0-1 and 2-3 hr postdose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39106541Bethoux 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.
- Individual participant dataSharing planned: No
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Multiple Sclerosis Spasticity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nabiximols in people with Spasticity in Participants With Multiple Sclerosis, run by Jazz Pharmaceuticals at 16 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Poland, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04657666, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.