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

NCT ID: NCT04203498

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2023-02-28

Brief Summary

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).

Detailed Description

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.

Conditions

Multiple Sclerosis (MS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nabiximols

Group Type: EXPERIMENTAL

Nabiximols

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

GW-1000-02; Sativex

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, United States

Neurostudies - Port Charlotte

Port Charlotte, Florida, United States

University of South Florida

Tampa, Florida, United States

Accel Research Sites - Enterprise

Tampa, Florida, United States

Shepherd Center

Atlanta, Georgia, United States

Consultants in Neurology - Northbrook

Northbrook, Illinois, United States

American Health Network of Indiana

Avon, Indiana, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

The Multiple Sclerosis Center For Innovations In Care

St Louis, Missouri, United States

Raleigh Neurology Associates - Raleigh Location

Raleigh, North Carolina, United States

University of Cincinnati (UC) Health

Dayton, Ohio, United States

Neurology Clinic - Cordova

Cordova, Tennessee, United States

Hope Neurology

Knoxville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Central Texas Neurology Consultants

Round Rock, Texas, United States

Poliklinika Choceň

Choceň, Pardubice, Czechia

Neurologie Taláb Radomír Doc. MUDr., CSc

Hradec Králové, , Czechia

Nemocnice Jihlava

Jihlava, , Czechia

Fakultní Nemocnice Královské Vinohrady

Prague, , Czechia

Krajská Zdravotní - Nemocnice Teplice

Teplice, , Czechia

Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD

Poznan, Greater Poland Voivodeship, Poland

Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Wromedica Centrum Zdrowia

Wroclaw, Lower Silesian Voivodeship, Poland

Centrum Medyczne Neuroprotect

Warsaw, Masovian Voivodeship, Poland

Centrum Medyczne Pratia - Warszawa

Warsaw, Masovian Voivodeship, Poland

Neuro-Medic Janusz Zbrojkiewicz

Katowice, Silesian Voivodeship, Poland

Wielospecjalistyczne Centrum Medyczne Ibismed

Zabrze, Silesian Voivodeship, Poland

SP ZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego w Łodzi

Lodz, , Poland

Centrum Medyczne Oporów

Lublin, , Poland

Neurologiczny NZOZ Centrum Leczenia SM Ośrodek Badań Klinicznych im. dr n. med. Hanki Hertmanowskiej Witosław Cieślak

Plewiska, , Poland

Wromedica Centrum Zdrowia

Wroclaw, , Poland

RESMEDICA Poradnia Neurologiczna

Kielce, Świętokrzyskie Voivodeship, Poland

Centrul Medical Clubul Sanatatii

Campulung Muscel, , Romania

Spitalul Municipal Caracal

Caracal, , Romania

Spitalul Clinic Cai Ferate Constanta

Constanța, , Romania

Spitalul Municipal Sf. Dr. Cosma si Damian Radauti

Radauti, , Romania

Barts Health NHS Trust

London, England, United Kingdom

Countries

United States; Czechia; Poland; Romania; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002623-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GWSP18023

Identifier Type: -

Identifier Source: org_study_id