Clinical trial NCT04203498: Safety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Therapy in Participants With Spasticity Due to Multiple Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Sclerosis (MS)
Keywords: Spasticity
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-12-18
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Change in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change in Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score
timeFrame: Week 8 and Week 12
measure: Number of Patients Reporting Any Treatment-emergent Adverse Events
timeFrame: From date of first dose of IMP up to 30 days after last dose, up to approximately 16 weeks
measure: Change From Baseline in Clinical Laboratory Test Values
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Erythrocytes
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Hemoglobin
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Hematocrit Ratio
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Blood Pressure
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Heart Rate
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Electrocardiogram Parameters
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Electrocardiogram Pulse Rate
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Weight
timeFrame: Baseline up to Week 12
measure: Change in Body Mass Index
timeFrame: Baseline up to Week 12
measure: Number of Patients With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Screening up to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine
state: Alabama
city: Port Charlotte
country: United States
facility: Neurostudies - Port Charlotte
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: Accel Research Sites - Enterprise
state: Florida
city: Atlanta
country: United States
facility: Shepherd Center
state: Georgia
city: Northbrook
country: United States
facility: Consultants in Neurology - Northbrook
state: Illinois
city: Avon
country: United States
facility: American Health Network of Indiana
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Saint Louis
country: United States
facility: The Multiple Sclerosis Center For Innovations In Care
state: Missouri
city: Raleigh
country: United States
facility: Raleigh Neurology Associates - Raleigh Location
state: North Carolina
city: Dayton
country: United States
facility: University of Cincinnati (UC) Health
state: Ohio
city: Cordova
country: United States
facility: Neurology Clinic - Cordova
state: Tennessee
city: Knoxville
country: United States
facility: Hope Neurology
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Choceň
country: Czechia
facility: Poliklinika Choceň
state: Pardubice
city: Hradec Králové
country: Czechia
facility: Neurologie Taláb Radomír Doc. MUDr., CSc
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava
city: Praha 10
country: Czechia
facility: Fakultní Nemocnice Královské Vinohrady
city: Teplice
country: Czechia
facility: Krajská Zdravotní - Nemocnice Teplice
city: Wrocław
country: Poland
facility: Wromedica Centrum Zdrowia
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych
state: Kujawsko-Pomorskie
city: Warszawa
country: Poland
facility: Centrum Medyczne Neuroprotect
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Medyczne Pratia - Warszawa
state: Mazowieckie
city: Katowice
country: Poland
facility: Neuro-Medic Janusz Zbrojkiewicz
state: Slaskie
city: Zabrze
country: Poland
facility: Wielospecjalistyczne Centrum Medyczne Ibismed
state: Slaskie
city: Kielce
country: Poland
facility: RESMEDICA Poradnia Neurologiczna
state: Swietokrzyskie
city: Poznań
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD
state: Wielkopolskie
city: Lublin
country: Poland
facility: Centrum Medyczne Oporów
city: Plewiska
country: Poland
facility: Neurologiczny NZOZ Centrum Leczenia SM Ośrodek Badań Klinicznych im. dr n. med. Hanki Hertmanowskiej Witosław Cieślak
city: Wrocław
country: Poland
facility: Wromedica Centrum Zdrowia
city: Łódź
country: Poland
facility: SP ZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego w Łodzi
city: Caracal
country: Romania
facility: Spitalul Municipal Caracal
city: Constanţa
country: Romania
facility: Spitalul Clinic Cai Ferate Constanta
city: Câmpulung
country: Romania
facility: Centrul Medical Clubul Sanatatii
city: Rădăuți
country: Romania
facility: Spitalul Municipal Sf. Dr. Cosma si Damian Radauti
city: London
country: United Kingdom
facility: Barts Health NHS Trust
state: England
Study officials:
References: