Evaluate the Maintenance of Effect After Long-term Treatment With Sativex® in Subjects With Symptoms of Spasticity Due to Multiple Sclerosis

NCT00702468 | Completed Phase 3 Results

• 1 other identifier: GWSP0702
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the maintenance of effect after long-term treatment with Sativex® in subjects with symptoms of spasticity due to Multiple Sclerosis (MS) who have been receiving long-term benefit from treatment with Sativex®.

Conditions

Spasticity; Multiple Sclerosis

Keywords

Spasticity; Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Who Experience Treatment Failure.

  The time to treatment failure was calculated as the number of days from the first day of treatment up to the day of treatment failure. The day of treatment failure was the earliest of:the day of premature cessation of study medication;the first day of the longest period, ending on the last day of treatment, where the mean spasticity NRS had increased by at least 20% and at least 1 unit from the treatment baseline; the day of a clinically relevant increase in anti-spasticity or disease modifying medication. The number of subjects who failed treatment were calculated.

  Week 1- Week 5

Secondary Outcomes (8)

• Change in Mean Daily Spasticity Severity as Measured on a Spasticity Severity 0-10 Numerical Rating Scale (NRS).

  Baseline (Week 1) to Week 5

• Change in Modified Ashworth Scale.

  Day 7 to Day 28

• Change in Motricity Index

  Week 2 and Week 5

• Timed 10-metre Walk.

  Week 2 and Week 5

• Daily Sleep Disruption NRS

  Week 1- Week 5

Study Arms (2)

Sativex

EXPERIMENTAL

Sativex

Drug: Sativex

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Sativex DRUG

containing delta-9-tetrahydrocannabinol (THC)(27 mg/ml):cannabidiol (CBD)(25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Dose: 100 µl oromucosal spray, as required for symptom relief

Also known as: GW-1000-02

Sativex

Placebo DRUG

Contains no active drug and is delivered in 100 microlitre actuations by a pump action oromucosal spray

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 MS.
• Received Sativex for the relief of spasticity for at least 12 weeks prior to screening and willing to stop dosing with their own supply for the duration of the study.
• Judged to have been receiving benefit from and shown tolerability to Sativex, in the investigators' and subjects' opinion.
• Takes a minimum dose of Sativex of two sprays per day.
• If receiving disease-modifying medications, these must have been at a stable dose for at least three months prior to screening, and willing to maintain this for the duration of the study.
• Has had a stable regimen for at least 30 days prior to study entry, for all medications and non-pharmacological therapies that may have an affect on spasticity; and willing to maintain this for the duration of the study (N.B. This should be three months prior to study entry, in the case of Interferon therapy).
• Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the study.
• Willing for his or her name to be notified to the responsible authorities for participation in this study

You may not qualify if:

• Has any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity.
• Unable to rate their level of spasticity or distinguish it from other MS symptoms.
• Currently receiving a prohibited medication (Botulinum Toxin, or Acomplia (Rimonabant), and unwilling to stop or comply for the duration of the study or had received said medication/ therapy within three months prior to the screening visit.
• Unwilling to stop their own Sativex treatment for the duration of the study.
• Any known or suspected immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
• Has evidence of cardiomyopathy.
• Has experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction.
• Has a QT interval of \> 450 ms (males) or \> 470 ms (females) at Visit 1.
• Has a secondary or tertiary atrioventricular (AV) block or sinus bradycardia (HR \<50bpm unless physiological) or sinus tachycardia (HR\>110bpm) at Visit 1.
• Has a diastolic blood pressure of \<50 mmHg or \>105 mmHg (when measured in a sitting position at rest for five minutes) prior to randomisation
• Has impaired renal function e.g. creatinine clearance is lower than 50ml/min at Visit 1 and is indicative of renal impairment.
• Has significantly impaired hepatic function, at Visit 1, in the investigator's opinion.
• 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 and for three months thereafter.
• Subjects who have received any IMP within the 12 weeks before Visit 1.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (1)

James Paget University Hospital NHS Foundation Trust

Gorleston-on-Sea, Norfolk, NR31 6LA, United Kingdom

Location

Related Publications (2)

• Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex(R) (nabiximols). Mult Scler. 2012 Feb;18(2):219-28. doi: 10.1177/1352458511419700. Epub 2011 Aug 30.

  PMID: 21878454 RESULT

• Di Marzo V, Centonze D. Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes. CNS Neurosci Ther. 2015 Mar;21(3):215-21. doi: 10.1111/cns.12358. Epub 2014 Dec 4.

  PMID: 25475413 DERIVED

MeSH Terms

Conditions

Muscle Spasticity; Multiple Sclerosis

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Richard Potts Clinical Operations Director
• Organization: GW Pharma Ltd

rp@gwpharm.com

+44 1353 616600

Study Officials

• William Notcutt, MB ChB, FRCA

  James Paget University Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2008
• First Posted: June 20, 2008
• Study Start: November 1, 2007
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: May 6, 2023
• Results First Posted: June 17, 2011

Record last verified: 2023-04

Locations

GB (1)