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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-002623-14 | EudraCT Number |
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This study was terminated based on a business decision by the Sponsor.
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nabiximols | Experimental |
| |
| Placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nabiximols | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period | The change in the average daily spasm count was assessed compared to the baseline period. | Baseline to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score | The MSSS-88 is a self-reported measure of the impact of spasticity (muscle stiffness and spasms) in MS. This 88-item scale captures the patient experience and impact of spasticity, including muscle stiffness, pain and discomfort, muscle spasms, effect on daily activities, ability to walk, body movement, patient feelings, and social functioning. Responses to individual questions can range from "1 - not at all bothered" to "4 - extremely bothered", ranging from 88 to 352 total score. Scores are summed and higher scores indicate poor clinical outcome. Least square means are being reported, with greater negative values indicating better outcome. |
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Inclusion Criteria:
Criteria at screening:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham School of Medicine | Birmingham | Alabama | 35233 | United States | ||
| Neurostudies - Port Charlotte |
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| ID | Title | Description |
|---|---|---|
| FG000 | Nabiximols | Patients randomized to receive GW-1000-2 (nabiximols) self-administered as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks. |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 1, 2021 | Feb 9, 2024 |
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| Placebo | 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. |
|
| Week 8 and Week 12 |
| Number of Patients Reporting Any Treatment-emergent Adverse Events | A TEAE is an adverse event that started, or worsened in severity or seriousness, following the first dose of the investigational medicinal product. | From date of first dose of IMP up to 30 days after last dose, up to approximately 16 weeks |
| Change From Baseline in Clinical Laboratory Test Values | Baseline up to Week 12 |
| Change From Baseline in Erythrocytes | Baseline up to Week 12 |
| Change From Baseline in Hemoglobin | Baseline up to Week 12 |
| Change From Baseline in Hematocrit Ratio | The hematocrit ratio measures the volume of red blood cells compared to the total blood volume. | Baseline up to Week 12 |
| Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | Baseline up to Week 12 |
| Change From Baseline in Blood Pressure | Baseline up to Week 12 |
| Change From Baseline in Heart Rate | Baseline up to Week 12 |
| Change From Baseline in Electrocardiogram Parameters | Baseline up to Week 12 |
| Change From Baseline in Electrocardiogram Pulse Rate | Baseline up to Week 12 |
| Change From Baseline in Weight | Baseline up to Week 12 |
| Change in Body Mass Index | Baseline up to Week 12 |
| Number of Patients With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) | 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. | Screening up to Week 12 |
| Port Charlotte |
| Florida |
| 33952 |
| United States |
| University of South Florida | Tampa | Florida | 33613 | United States |
| Accel Research Sites - Enterprise | Tampa | Florida | 33634 | United States |
| Shepherd Center | Atlanta | Georgia | 30309 | United States |
| Consultants in Neurology - Northbrook | Northbrook | Illinois | 60062 | United States |
| American Health Network of Indiana | Avon | Indiana | 46123 | United States |
| Ochsner Medical Center | New Orleans | Louisiana | 70121 | United States |
| The Multiple Sclerosis Center For Innovations In Care | St Louis | Missouri | 63131 | United States |
| Raleigh Neurology Associates - Raleigh Location | Raleigh | North Carolina | 27607 | United States |
| University of Cincinnati (UC) Health | Dayton | Ohio | 45417 | United States |
| Neurology Clinic - Cordova | Cordova | Tennessee | 38018 | United States |
| Hope Neurology | Knoxville | Tennessee | 37922 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Central Texas Neurology Consultants | Round Rock | Texas | 78681 | United States |
| Poliklinika Choceň | Choceň | Pardubice | 565 01 | Czechia |
| Neurologie Taláb Radomír Doc. MUDr., CSc | Hradec Králové | 500 03 | Czechia |
| Nemocnice Jihlava | Jihlava | 586 01 | Czechia |
| Fakultní Nemocnice Královské Vinohrady | Prague | 100 34 | Czechia |
| Krajská Zdravotní - Nemocnice Teplice | Teplice | 415 29 | Czechia |
| Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD | Poznan | Greater Poland Voivodeship | 61-853 | Poland |
| Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych | Bydgoszcz | Kuyavian-Pomeranian Voivodeship | 85-163 | Poland |
| Wromedica Centrum Zdrowia | Wroclaw | Lower Silesian Voivodeship | 51-685 | Poland |
| Centrum Medyczne Neuroprotect | Warsaw | Masovian Voivodeship | 01-684 | Poland |
| Centrum Medyczne Pratia - Warszawa | Warsaw | Masovian Voivodeship | 01-868 | Poland |
| Neuro-Medic Janusz Zbrojkiewicz | Katowice | Silesian Voivodeship | 40-555 | Poland |
| Wielospecjalistyczne Centrum Medyczne Ibismed | Zabrze | Silesian Voivodeship | 41-800 | Poland |
| SP ZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego w Łodzi | Lodz | 90-001 | Poland |
| Centrum Medyczne Oporów | Lublin | 20-855 | Poland |
| Neurologiczny NZOZ Centrum Leczenia SM Ośrodek Badań Klinicznych im. dr n. med. Hanki Hertmanowskiej Witosław Cieślak | Plewiska | 62-064 | Poland |
| Wromedica Centrum Zdrowia | Wroclaw | 51-685 | Poland |
| RESMEDICA Poradnia Neurologiczna | Kielce | Świętokrzyskie Voivodeship | 25-726 | Poland |
| Centrul Medical Clubul Sanatatii | Campulung Muscel | 115100 | Romania |
| Spitalul Municipal Caracal | Caracal | 235200 | Romania |
| Spitalul Clinic Cai Ferate Constanta | Constanța | 900123 | Romania |
| Spitalul Municipal Sf. Dr. Cosma si Damian Radauti | Radauti | 725400 | Romania |
| Barts Health NHS Trust | London | England | E1 1BB | United Kingdom |
Patients randomized to receive placebo self-administered as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks.
| Safety Analysis Set |
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| COMPLETED |
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| NOT COMPLETED |
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Baseline characteristics are reported from the Full Analysis Set defined as all patients from the Safety Analysis Set who signed the informed consent and are randomized by interactive response technology.
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| ID | Title | Description |
|---|---|---|
| BG000 | Nabiximols | Patients randomized to receive GW-1000-2 (nabiximols) self-administered as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks. |
| BG001 | Placebo | Patients randomized to receive placebo self-administered as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period | The change in the average daily spasm count was assessed compared to the baseline period. | Average daily spasm count was assessed in participants with available data in the Full Analysis Set defined as all patients from the Safety Analysis Set who signed the informed consent and are randomized by interactive response technology.. | Posted | Least Squares Mean | Standard Error | daily spasm count | Baseline to Week 12 |
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| Secondary | Change in Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score | The MSSS-88 is a self-reported measure of the impact of spasticity (muscle stiffness and spasms) in MS. This 88-item scale captures the patient experience and impact of spasticity, including muscle stiffness, pain and discomfort, muscle spasms, effect on daily activities, ability to walk, body movement, patient feelings, and social functioning. Responses to individual questions can range from "1 - not at all bothered" to "4 - extremely bothered", ranging from 88 to 352 total score. Scores are summed and higher scores indicate poor clinical outcome. Least square means are being reported, with greater negative values indicating better outcome. | Changes in Multiple Sclerosis Spasticity Scale were assessed in participants with available data in the Full Analysis Set defined as all patients from the Safety Analysis Set who signed the informed consent and are randomized by interactive response technology. | Posted | Least Squares Mean | Standard Error | unit on a scale | Week 8 and Week 12 |
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| Secondary | Number of Patients Reporting Any Treatment-emergent Adverse Events | A TEAE is an adverse event that started, or worsened in severity or seriousness, following the first dose of the investigational medicinal product. | Treatment-emergent adverse events were assessed in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Count of Participants | Participants | From date of first dose of IMP up to 30 days after last dose, up to approximately 16 weeks |
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| Secondary | Change From Baseline in Clinical Laboratory Test Values | Clinical laboratory values were assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | 10^9 cells/liter | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Erythrocytes | Erythrocytes were assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | 10^12 cells/liter | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Hemoglobin | Hemoglobin was assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | g/dL | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Hematocrit Ratio | The hematocrit ratio measures the volume of red blood cells compared to the total blood volume. | Hematocrit ratio was assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | ratio of packed cells to total volume | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | Erythrocyte mean corpuscular hemoglobin was assessed patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | pg | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Blood Pressure | Blood pressure was assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | mmHg | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Heart Rate | Heart rate was assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | beats/minute | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Electrocardiogram Parameters | Electrocardiogram parameters were assessed in patients with available data in the Safety Analysis Set. defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | msec | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Electrocardiogram Pulse Rate | Electrocardiogram heart rate was assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | beats/min | Baseline up to Week 12 |
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| Secondary | Change From Baseline in Weight | Weight was assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | kg | Baseline up to Week 12 |
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| Secondary | Change in Body Mass Index | Body mass index was assessed in patients with available data in the Safety Analysis Set defined as all participants who received at least 1 dose of study intervention in the study. | Posted | Mean | Standard Deviation | kg/m^2 | Baseline up to Week 12 |
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| Secondary | Number of Patients With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) | 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. | Suicidal ideation or behavior was assessed in the Safety Analysis Set. defined as all participants who received at least 1 dose of study intervention in the study | Posted | Count of Participants | Participants | Screening up to Week 12 |
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Adverse event data were collected from baseline up to 14 days after the end of treatment visit, up to Day 99 (safety follow up visit).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nabiximols | Patients randomized to receive GW-1000-2 (nabiximols) self-administered as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks. | 0 | 67 | 3 | 67 | 46 | 67 |
| EG001 | Placebo | Patients randomized to receive placebo self-administered as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks. | 0 | 70 | 5 | 70 | 19 | 70 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Arthritis bacterial | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| SARS-CoV-2 test positive | Investigations | MedDRA24.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA24.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA24.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA24.0 | Systematic Assessment |
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| Taste disorder | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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Study enrollment was ended early and did not reach the planned number of participants.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosure & Transparency | Jazz Pharmaceuticals Inc. | 215-832-3750 | ClinicalTrialDisclosure@JazzPharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 22, 2022 | Feb 9, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D009128 | Muscle Spasticity |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009122 | Muscle Hypertonia |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C587251 | nabiximols |
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| ≥18 years to <45 years |
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| ≥45 years to <65 years |
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| ≥65 years |
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| Male |
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| Black or African American |
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| Asian |
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| American Indian or Alaska Native |
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| Native Hawaiian or Other Pacific Islander |
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| Other |
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| Week 5 to 8 |
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| Week 9 to 12 |
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