Clinical trial NCT01610713: An Study to Investigate the Efficacy of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis
Official title: Double Blind, Randomised, Parallel Group, Placebo Controlled Trial of a Combination of THC and CBD in Patients With Multiple Sclerosis, Followed by an Open Label Assessment and Study Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-06-04
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An open-label extension study in which patients with multiple sclerosis received GW-1000-02 \[named Sativex® in Canada and also named Sativex® Oromucosal Spray\] for four weeks in an open-label manner.

Detailed description: Subjects who took part in GWMS0001 Part A were invited to continue to receive GW-1000-02 in this four-week open-label part of the study. Subjects received open-label cannabinoid extract (GW-1000-02) for four weeks, either with or without peppermint flavouring, according to their study centre. Subjects who completed the study could choose to continue receiving GW-1000-02 by entering the long-term safety extension follow-on study.

Eligibility criteria: Inclusion Criteria:

* Aged at least 18 years.
* Multiple Sclerosis of any type.
* Stable Multiple Sclerosis symptomatology during the four weeks before study entry.
* Symptoms of the required severity (\>50 mm on a 100 mm Visual Analogue Scale severity scale) in least one of the specified impairment categories; spasticity, muscle spasms, disturbed bladder control, neuropathic pain, limb tremor.
* A stable medication regime during the four weeks before study entry.
* Willing to abstain from cannabis or cannabinoids for at least seven days before study entry, and during the study.
* Agreed either to use effective contraception during the study and for three months thereafter, or had been surgically sterilised or, if female, were post-menopausal.
* Clinically acceptable laboratory results for pre-study screening.
* Willing and able to undertake and comply with all study requirements.
* Willing and able to read, consider and understand the subject information and consent form and give written informed consent. Subjects unable to read or to sign the document procedures were treated as detailed in the Declaration of Helsinki.
* Willing for their general practitioner, and consultant if appropriate, to be informed of study participation.
* Willing for their name to be notified to Home Office for participation in the study.

Exclusion Criteria:

* Known or strongly suspected to be abusing drugs, including alcohol.
* Not prepared to abstain from cannabis or cannabinoids during the study.
* Current or past addiction to cannabis.
* Known or suspected to have had an adverse reaction to cannabinoids causing psychosis or other severe psychiatric illness.
* History of any type of schizophrenia, any other psychotic illness, or other significant psychiatric illness or personality disorder other than depression associated with chronic illness.
* Received any drug containing levodopa (Sinemet®, Sinemet plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®).
* Serious cardiovascular disorder including angina, uncontrolled hypertension, or an uncontrolled symptomatic cardiac arrhythmia.
* Significant renal or hepatic impairment as shown in medical history or indicated by laboratory results.
* History of epilepsy.
* Terminal illness or other condition in which placebo medication would be inappropriate.
* Pregnant, lactating or at risk of pregnancy.
* Participated in any other clinical research study during the 12 weeks before study entry.
* Planned hospital admission between study entry and Visit 6.
* Planned travel outside the UK between study entry and Visit 6.

Primary outcomes:
measure: Change From Mean Part A Primary Impairment Visual Analogue Scale Score (After 6 Weeks) at the End of Four Weeks of Open-label Treatment (10 Weeks Total)
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
Secondary outcomes:
measure: Change From Mean Part A Guy's Neurological Disability Scale Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Care-Giver Strain Index Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Reading Visual Acuity Test Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Ashworth Scale Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Short Orientation Memory Concentration Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Barthel Activities for Daily Living Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Total Adult Memory and Information Processing Battery Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Beck's Depression Inventory (BDI-II) Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Fatigue Severity Scale Questionnaire Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Rivermead Mobility Index Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Total 28-item General Health Questionnaire Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Nine Hole Peg Test Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Total Bladder Control Questionnaire Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Tremor Activities of Daily Living Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Mean Part A Sleep Quality 100 mm Visual Analogue Scale Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Incidence of Adverse Events as a Measure of Patient Safety
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Sleep Amount 100 mm Visual Analogue Scale Score at the End of Open-label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Feeling Upon Wakening 100 mm Visual Analogue Scale Score at the End of Open-Label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Spasticity Visual Analogue Scale Score at the End of Open-Label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Pain Visual Analogue Scale Score at the End of Open-Label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Muscle Spasm Visual Analogue Scale Score at the End of Open-Label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Tremor Visual Analogue Scale Score at the End of Open-Label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Bladder Problems Visual Analogue Scale Score at the End of Open-Label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Change From Part A Mean Ten-metre Mobility Score at the End of Open-Label Treatment
timeFrame: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
measure: Subject Global Opinion of Effect on Multiple Sclerosis at the End of Open-label Treatment
timeFrame: End of Part B (week 10)
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Rivermead Rehabilitation Centre
Study officials:
References:
citation: Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004 Aug;10(4):434-41. doi: 10.1191/1352458504ms1082oa.
citation: 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.