A Long-term Safety Extension Study of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT01610687
First received: May 31, 2012
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

An extension study to evaluate the long-term safety, tolerability and efficacy of GW-1000-02 treatment in multiple sclerosis.


Condition Intervention Phase
Multiple Sclerosis
Spasticity
Drug: GW-1000-02
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 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

Resource links provided by NLM:


Further study details as provided by GW Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • Incidence of Adverse Events as a Measure of Patient Safety [ Time Frame: up to1206 days ] [ Designated as safety issue: Yes ]
    The number of patients who experienced an adverse event during the course of this extension study is presented


Secondary Outcome Measures:
  • Mean Number of Sprays of Study Medication Taken During the Last 6 Days of Treatment [ Time Frame: up to 1206 days ] [ Designated as safety issue: No ]
    A categorical summary was produced of the mean number of sprays per day during the last six days of treatment, and the mean number of sprays was rounded to the nearest whole number for categorisation.

  • Change From Baseline in Mean Intoxication 100 mm Visual Analogue Scale Scores at Week 18. [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    Intoxication levels were recorded on a Visual Analogue Scale, where 0 equals 'no intoxication' and 10 equals 'extreme intoxication'. A decrease in score indicates an improvement in intoxication levels.

  • Investigator Assessed Global Severity Score at Week 18 [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    The investigator rated the global severity of the subject's primary condition since entry into the study using a five-point verbal rating scale-5: 1=much worse, 2=worse, 3=no change, 4=better, 5=much better. The number of patients which were considered better or much better (scores 4 and 5) at week 18 of the study better is presented.

  • Change From Baseline in the Mean Pain 100 mm Visual Analogue Scale Score at Week 18 [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    A clinical assessment of pain was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no pain and 100 = worst possible pain. A decrease in score indicates an improvement.

  • Change From Baseline in the Mean Spasticity 100 mm Visual Analogue Scale Score at Week 18 [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    A clinical assessment of spasticity was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no spasticity and 100 = worst possible spasticity. A decrease in score indicates an improvement.

  • Change From Baseline in the Mean Tremor 100 mm Visual Analogue Scale Score at Week 18 [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    A clinical assessment of tremor was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no tremor and 100 = worst possible tremor. A decrease in score indicates an improvement.

  • Change From Baseline in the Mean Bladder Problems 100 mm Visual Analogue Scale Score at Week 18 [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    A clinical assessment of bladder problems was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no bladder problems and 100 = worst possible bladder problems. A decrease in score indicates an improvement.


Enrollment: 137
Study Start Date: July 2001
Study Completion Date: February 2005
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GW-1000-02
Active treatment
Drug: GW-1000-02
Contained THC and CBD as extract of Cannabis sativa L. Each 100 μl actuation delivered a dose containing 2.7 mg THC and 2.5mg CBD. The maximum permitted dose was eight actuations (22 mg THC and 20 mg CBD) in any three hour period, and 48 actuations (130 mg THC and 120 mg CBD) in any 24 hour period.
Other Name: Sativex

Detailed Description:

Patients who participated in the placebo controlled phase of this study and opted to continue receiving open label GW-1000-02 entered the follow-on extension of the study and completed symptom assessments to determine whether they were continuing to receive clinical benefit from GW-1000-02.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610687

Locations
United Kingdom
Rivermead Rehabilitation Centre
Oxford, United Kingdom, OX3 7LD
Sponsors and Collaborators
GW Pharmaceuticals Ltd.
Investigators
Principal Investigator: Derick Wade, FRCP MD Rivermead Rehabilitation Centre
  More Information

Publications:
Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01610687     History of Changes
Other Study ID Numbers: GWMS0001 EXT
Study First Received: May 31, 2012
Results First Received: July 11, 2012
Last Updated: June 18, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Multiple Sclerosis
Muscle Spasticity
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes
Dronabinol
Hallucinogens
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 01, 2014