A Study of the Safety and Effectiveness of Sativex®, for the Relief of Symptoms of Spasticity in Subjects With Multiple Sclerosis (MS) - Full Text View

Sponsored by:	GW Pharmaceuticals Ltd.
Information provided by:	GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:	NCT00681538

Purpose

The purpose of this study is to determine whether Sativex® versus Placebo is effective in the relief of symptoms of spasticity in subjects with multiple sclerosis.

Condition	Intervention	Phase
Spasticity Multiple Sclerosis	Drug: Sativex® Drug: Placebo	Phase III

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Propylene glycol Cannabis GW-1000 Ethanol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Further study details as provided by GW Pharmaceuticals Ltd.:

Primary Outcome Measures:

The mean spasticity NRS score over the last seven days of the evaluable period. [ Time Frame: Week 17 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of subjects showing an improvement of 30% or more and 50% or more in their primary endpoint from baseline. [ Time Frame: Week 1 to Week 17 (last seven days of treatment) ] [ Designated as safety issue: No ]
Spasm frequency (number of spasms per day). [ Time Frame: Week 1 to Week 17 ] [ Designated as safety issue: No ]
Sleep disruption (daily 11-point NRS). [ Time Frame: Week 1 to Week 17 ] [ Designated as safety issue: No ]
Modified Ashworth Scale. [ Time Frame: Weeks 2, 6 and 18 ] [ Designated as safety issue: No ]
Motricity Index [ Time Frame: Weeks 2,6 and 18 ] [ Designated as safety issue: No ]
Timed 10-metre walk. [ Time Frame: Weeks 2,6, 10, 14 and 18 ] [ Designated as safety issue: No ]
Barthel Activities of Daily Living (ADL) Index. [ Time Frame: Weeks 2, 6 and 18 ] [ Designated as safety issue: No ]
Carer, Physician and Subject global impressions of change. [ Time Frame: Weeks 6, 10 , 14 and 18 ] [ Designated as safety issue: No ]
Carer global impressions of change for ease of transfer. [ Time Frame: weeks 6, 10, 14 and 18 ] [ Designated as safety issue: No ]
Spasm frequency (number of spasms per day). [ Time Frame: Weeks 1 to Week 17 ] [ Designated as safety issue: No ]
Adverse events (AEs). [ Time Frame: Weeks 1 to Week 18 ] [ Designated as safety issue: Yes ]
Clinical laboratory tests. [ Time Frame: Weeks 1, 6 and 18 ] [ Designated as safety issue: Yes ]
Vital signs. [ Time Frame: weeks 1, 2, 6, 10, 14 and 18 ] [ Designated as safety issue: Yes ]
Oral Examination. [ Time Frame: Weeks 2,6 & 18 ] [ Designated as safety issue: Yes ]
QOL Assessments: EuroQoL quality of life questionnaire (EQ-5D); Short Form 36 Health Survey (SF-36). [ Time Frame: weeks 2, 6 and 18 ] [ Designated as safety issue: No ]
Mood Assessment: Beck Depression Inventory - II (BDI-II) [ Time Frame: Weeks 2, 6 and 18 ] [ Designated as safety issue: No ]

Estimated Enrollment:	488
Study Start Date:	January 2008
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	Drug: Sativex® containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum dose within any 24-hour interval is 12 sprays (THC 32.4 mg: CBD 30 mg)
B: Placebo Comparator	Drug: Placebo containing ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and colourings FD&C Yellow No.5 (E102 tartrazine) (0.0260%), FD&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Willing and able to give written informed consent for participation in the study.
Male or female, aged 18 years or above.
Subject is able (in the investigator's opinion) and willing to comply with all study requirements.
Diagnosed with any disease sub-type of MS of at least six months duration.
Spasticity due to MS of at least three months duration, which is not wholly relieved with current anti-spasticity therapy, and which is expected to remain stable for the duration of the study.
Subject fulfils at least one of the two criteria below. Subject must be either: Currently established on a regular dose of anti-spasticity therapy or Previously tried and failed, or could not tolerate suitable anti-spasticity therapy.
Subject is currently receiving a stable regimen (for at least 30 days prior to study entry) of all medications that may have an effect on spasticity; and willing to maintain this for the duration of the study. If the subject is currently taking disease-modifying medication, this must be at a stable dose for at least three months prior to the screening visit; the dose must also remain stable for the duration of the study.
Willing for his or her name to be notified to his or her primary care physician, and consultant and the responsible authorities for participation in this study, as applicable.

Exclusion Criteria:

Any concomitant disease or disorder that has spasticity-like symptoms or that may influence the subject's level of spasticity.
Subject's medical history suggests that relapse/remission is likely to occur during the study (over the next 19 weeks) which, in the opinion of the investigator, is expected to influence the subject's spasticity.
Currently receiving a prohibited medication and unwilling to stop for the stated period prior to the screening visit and for the duration of the study.
Any known or suspected history of: schizophrenia or other psychotic illness;diagnosed dependence disorder;poorly controlled epilepsy or recurrent seizures;hypersensitivity to cannabinoids.
Significant cardiac, renal or hepatic disease.
Female subjects of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for three months thereafter.
Female subject who is pregnant, lactating or planning pregnancy during the course of the study or for three months thereafter.
Subjects who have received an IMP within the 12 weeks before Visit 1.
Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study.
Following a physical examination, the subject has any abnormalities that, in the opinion of the investigator, would prevent them from safely participating in the study.
Unwilling to abstain from donation of blood during the study.
Travel outside the country of residence planned during the study.
Subjects previously randomised into this study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00681538

Locations

United Kingdom, Northampton
Department of Neurology, Northampton General Hospital
Cliftonville, Northampton, United Kingdom, NN1 5BD

Sponsors and Collaborators

GW Pharmaceuticals Ltd.

Investigators

Principal Investigator:

Paul Davies, MRCP, FRCP

Department of Neurology

More Information

Responsible Party:	GW Pharmaceuticals Ltd. ( Carolina Fernandez / Senior Clinical Project Manager )
Study ID Numbers:	GWSP0604
Study First Received:	May 19, 2008
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00681538
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency; Czech Republic: State Institute for Drug Control; Spain: Spanish Agency of Medicines; Italy: Ethics Committee; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by GW Pharmaceuticals Ltd.:

Spasticity
Multiple Sclerosis

Study placed in the following topic categories:

Autoimmune Diseases
Demyelinating Diseases
Sclerosis
Demyelinating diseases
Signs and Symptoms
Muscle Spasticity
Multiple Sclerosis

Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Demyelinating Autoimmune Diseases, CNS
Neurologic Manifestations
Autoimmune Diseases of the Nervous System
Ethanol

Additional relevant MeSH terms:

Neuromuscular Manifestations
Pathologic Processes
Immune System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on January 30, 2009