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

NCT ID: NCT00702468

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2009-01-31

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®.

Detailed Description

This five week (one week baseline and four weeks randomised treatment period), multi-centre, placebo controlled, parallel group, randomized withdrawal study will evaluate the maintenance of effect after long-term treatment with Sativex® in subjects with symptoms of spasticity due to MS who have been receiving long-term benefit from treatment with Sativex®. Subjects will be selected from the Supply of Unlicensed Sativex® (SUS) or named patient supply programmes and must have been receiving Sativex® for at least 12 weeks prior to study entry. Following informed consent and screening, eligible subjects will enter the study (Visit 1, Day 1) and commence a seven day open label baseline period, before returning for a randomisation visit (Visit 2, Day 7), at which point they are randomised to receive either Sativex® or placebo (randomised withdrawal period). Subjects will return to the centre for an end of study visit at week five (Visit 3, Day 35) or earlier if they withdraw from treatment. Spasticity and sleep disruption review and dosing diaries will be completed each day from the start of the baseline period until completion or withdrawal.

Conditions

Spasticity; Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Sativex

Sativex

Group Type: EXPERIMENTAL

Sativex

Intervention Type: 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

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Sativex

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

GW-1000-02

Eligibility 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 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

Exclusion Criteria

• 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.
• 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, 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.
• Travel outside the UK planned during the study.
• Unwilling to abstain from donation of blood during the study.
• Subjects previously randomised into this study.

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

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Notcutt, MB ChB, FRCA

Role: PRINCIPAL_INVESTIGATOR

James Paget University Hospital NHS Foundation Trust

Locations

James Paget University Hospital NHS Foundation Trust

Gorleston-on-Sea, Norfolk, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 21878454 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25475413 (View on PubMed)

Other Identifiers

GWSP0702

Identifier Type: -

Identifier Source: org_study_id