A Study of the Long-term Safety of Sativex Use

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01606137
• Collaborator: (none)
• Enrollment: 507
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 14.9

Study Details

Study Description

Brief Summary

Subjects who had previously received GW-1000-02 in a GW study who opted to continue using it in the long-term were monitored for ongoing tolerability and evidence of clinical benefit.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis; Spasticity; Pain	Drug: GW-1000-02	Phase 3

Detailed Description

Subjects who had previously participated in a placebo controlled GW clinical study were screened and if eligible began dosing with GW-1000-02. Subjects were reviewed for tolerability and evidence of clinical benefit at weeks two and four and then every eight weeks. Subjects self-titrated to symptom resolution or maximum tolerated/allowable dose of 130 mg THC and 120 mg CBD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 507 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-term, Open Label, Safety and Tolerability Study of Cannabis Based Medicine Extract in Patients Who Have Participated in a GW Clinical Study Using Cannabis Based Medicine.
• Study Start Date: Feb 1, 2002
• Actual Primary Completion Date: Dec 1, 2004
• Actual Study Completion Date: Dec 1, 2004

Arms and Interventions

Arm

Intervention/Treatment

Experimental: GW-1000-02 Active treatment

Drug: GW-1000-02; Contained delta-9-tetrahydrocannabinol (THC) (27 mg/ml) and cannabidiol (CBD) (25 mg/ml) as extract of Cannabis sativa L., with peppermint oil, 0.05% (v/v), in ethanol:propylene glycol (50:50) excipient. Each 100 μl actuation of the pump action spray delivered 2.7 mg THC and 2.5 mg CBD. A maximum daily exposure of 130 mg THC was specified by the UK regulatory authority authorisation.; Other Names: Sativex

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events as a Measure of Subject Safety. [Up to 1051 days]

   Following data entry, all adverse events were medically encoded using the Medical Dictionary for Regulatory Activities (MedDRA) 6.0. All subjects who experienced an adverse event during the treatment period is presented.

Secondary Outcome Measures

1. Change From Parent Study Baseline in Spasticity 0-10 Numerical Rating Scale Score After 52 Weeks of Treatment. [0 - 52 weeks]

   Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.

2. Change From Parent Study Baseline in Central Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. [0 - 52 weeks.]

   Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.

3. Change From Parent Study Baseline in Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment in Multiple Sclerosis Subjects. [0 - 52 weeks.]

   Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.

4. Change From Parent Study Baseline in Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. [0 - 52 weeks.]

   Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.

5. Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. [Up to 1051 days]

   Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.

6. Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. [Up to 1051 days]

   Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.

7. Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. [Up to 1051 days]

   Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.

8. Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. [Up to 1051days]

   Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.

9. Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. [Up to 1051]

   Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.

10. Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. [Up to 1051 days]

    Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.

11. Subject Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. [Up to 1051 days]

    Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.

12. Investigator Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. [Up to 1051 days.]

    Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.

13. Investigator Global Assessment at the Last Study Visit in Subjects With Neuropathic Pain Due to Multiple Sclerosis. [Up to 1051 days]

    Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.

14. Investigator Global Assessment at the Last Study Visit in Subjects With Central Neuropathic Pain. [Up to 1051 days.]

    Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.

15. Investigator Global Assessment at the Last Study Visit in Subjects With Pain. [Up to 1051 days.]

    Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.

16. Investigator Global Assessment at the Last Study Visit in Subjects With Multiple Sclerosis. [Up to 1051 days.]

    Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing and able to give informed consent.

• Male or female aged 18 years or above.

• Diagnosed with a condition categorised as one of the following: multiple sclerosis, spinal cord conditions, peripheral nerve injury or central nervous system damage associated with vascular, traumatic, infective, genetic or metabolic disease and whose symptom(s) were not wholly relieved by currently available therapy, prior to the previous study of GW-1000-02 or placebo.

• Had participated in a GW clinical study using GW-1000-02 within the previous month.

• Had shown tolerability to the study medication during the previous GW study.

• Was expected, by the investigator, to gain clinical benefit from receiving long-term GW-1000-02.

• Were willing, if female and of child bearing potential or male subjects with a partner of child bearing potential, to ensure that effective contraception was used during the study and for three months thereafter.

• Had not used cannabinoids (cannabis, Marinol or Nabilone) for at least seven days before Visit 1 (the exception being GW-1000-02 given as study medication) and were willing to abstain from any use of cannabis during the study.

• Recent (within seven days) haematology and blood chemistry that was normal or considered clinically acceptable in view of the subjects underlying condition.

• Able (in the investigators opinion) and willing to comply with all study requirements.

• Willing for the Home Office to be notified of his or her participation in the study.

• Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

• History of serious psychiatric illness, including schizophrenia, other psychotic illness or severe personality disorder other than depression associated with the underlying condition.

• Known or strongly suspected of alcohol or substance abuse or considered by the investigator to have been at risk of alcohol or substance abuse.

• Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.

• History of epilepsy or convulsions.

• Significant renal or hepatic impairment.

• Terminally ill.

• Any other significant disease or disorder which, in the opinion of the investigator, may have either put the subject at risk because of participation in the study, or may have influenced the result of the study, or the subject's ability to participate in the study.

• Female subjects who were pregnant, lactating or planning pregnancy during the course of the study.

• Regular levodopa (Sinemet, Sinemet Plus, Levodopa, L-dopa, Madopar, Benserazide) therapy within seven days of study entry.

• Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication.

• Known or suspected adverse reaction to cannabinoids.

• Donation of blood during the study.

• Previous participation in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gartnavel General Hospital	Glasgow		United Kingdom	G12 0YN

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

• Principal Investigator: Michael Serpell, ChB FRCA, Gartnavel General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01606137
• Other Study ID Numbers: GWEXT0102
• First Posted: May 25, 2012
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Additional relevant MeSH terms: Multiple Sclerosis; Nabiximols

Study Results

Participant Flow

Arm/Group Title	GW-1000-02
Arm/Group Description	Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). The maximum permitted dose of was eight actuations in any three hour period, and 48 actuations in any 24 hour period (THC 130 mg : CBD 120 mg).
Period Title: Overall Study
STARTED	507
COMPLETED	245
NOT COMPLETED	262

Baseline Characteristics

Arm/Group Title	GW-1000-02
Arm/Group Description	Active treatment
Overall Participants	507
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	458 90.3%
>=65 years	49 9.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (12.3)
Sex: Female, Male (Count of Participants)
Female	288 56.8%
Male	219 43.2%
Region of Enrollment (participants) [Number]
United Kingdom	507 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Events as a Measure of Subject Safety.
Description	Following data entry, all adverse events were medically encoded using the Medical Dictionary for Regulatory Activities (MedDRA) 6.0. All subjects who experienced an adverse event during the treatment period is presented.
Time Frame	Up to 1051 days

Outcome Measure Data

Analysis Population Description

All subjects who took part in the extension study were included in the analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	507
Number [participants]	477 94.1%

2. Secondary Outcome

Title	Change From Parent Study Baseline in Spasticity 0-10 Numerical Rating Scale Score After 52 Weeks of Treatment.
Description	Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.
Time Frame	0 - 52 weeks

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a parent randomised controlled trial (RCT) investigating the efficacy of GW-1000-02 in the treatment of spasticity associated with multiple sclerosis, and who received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	61
Mean (Standard Deviation) [units on a scale]	-1.83 (2.41)

3. Secondary Outcome

Title	Change From Parent Study Baseline in Central Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment.
Description	Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.
Time Frame	0 - 52 weeks.

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a central neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	62
Mean (Standard Deviation) [units on a scale]	-2.96 (2.03)

4. Secondary Outcome

Title	Change From Parent Study Baseline in Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment in Multiple Sclerosis Subjects.
Description	Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.
Time Frame	0 - 52 weeks.

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a neuropathic pain in multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	63
Mean (Standard Deviation) [units on a scale]	-3.11 (1.90)

5. Secondary Outcome

Title	Change From Parent Study Baseline in Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment.
Description	Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = "best possible" and 10 = "worst possible". A negative value indicates an improvement in score from baseline.
Time Frame	0 - 52 weeks.

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	131
Mean (Standard Deviation) [units on a scale]	-2.57 (2.02)

6. Secondary Outcome

Title	Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.
Time Frame	Up to 1051 days

Outcome Measure Data

Analysis Population Description

All multiple sclerosis subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	98
Number [participants]	75 14.8%

7. Secondary Outcome

Title	Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.
Time Frame	Up to 1051 days

Outcome Measure Data

Analysis Population Description

All multiple sclerosis subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	98
Number [participants]	76 15%

8. Secondary Outcome

Title	Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.
Time Frame	Up to 1051 days

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	168
Number [participants]	112 22.1%

9. Secondary Outcome

Title	Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.
Time Frame	Up to 1051days

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	168
Number [participants]	111 21.9%

10. Secondary Outcome

Title	Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Pain.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.
Time Frame	Up to 1051

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	314
Number [participants]	193 38.1%

11. Secondary Outcome

Title	Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Pain.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.
Time Frame	Up to 1051 days

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	314
Number [participants]	190 37.5%

12. Secondary Outcome

Title	Subject Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented.
Time Frame	Up to 1051 days

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	286
Number [participants]	199 39.3%

13. Secondary Outcome

Title	Investigator Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects.
Description	Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented.
Time Frame	Up to 1051 days.

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	287
Number [participants]	200 39.4%

14. Secondary Outcome

Title	Investigator Global Assessment at the Last Study Visit in Subjects With Neuropathic Pain Due to Multiple Sclerosis.
Description	Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.
Time Frame	Up to 1051 days

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a parent RCT investigation neuropathic pain due to multiple sclerosis, and who received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	98
Number [participants]	30 5.9%

15. Secondary Outcome

Title	Investigator Global Assessment at the Last Study Visit in Subjects With Central Neuropathic Pain.
Description	Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.
Time Frame	Up to 1051 days.

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a central neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	166
Number [participants]	83 16.4%

16. Secondary Outcome

Title	Investigator Global Assessment at the Last Study Visit in Subjects With Pain.
Description	Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.
Time Frame	Up to 1051 days.

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	312
Number [participants]	122 24.1%

17. Secondary Outcome

Title	Investigator Global Assessment at the Last Study Visit in Subjects With Multiple Sclerosis.
Description	Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of "much worse", "worse", "no change", "better", "much better". The number of subjects rated by the investigator as "better" or "much better" at the last study visit is presented.
Time Frame	Up to 1051 days.

Outcome Measure Data

Analysis Population Description

All subjects who entered the study from a multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.

Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
Measure Participants	284
Number [participants]	87 17.2%

Adverse Events

Time Frame	All adverse events occurring from the extension study onset to the last study visit (up to 1051 days) were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected.
Adverse Event Reporting Description	All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Arm/Group Title	GW-1000-02
Arm/Group Description	Each 100 ul actuation contains 27 mg THC and 25 mg CBD. A maximum of 48 actuations (130 mg of THC 120 and mg of CBD) was permitted in any 24 hour period.
All Cause Mortality
	GW-1000-02
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	GW-1000-02
	Affected / at Risk (%)	# Events
Total	74/507 (14.6%)
Cardiac disorders
CARDIAC FAILURE CONGESTIVE	1/507 (0.2%)
VENTRICULAR BIGEMINY	1/507 (0.2%)
Eye disorders
CORNEAL ULCER	1/507 (0.2%)
EYELID OEDEMA	1/507 (0.2%)
Gastrointestinal disorders
ABDOMINAL PAIN NOT OTHERWISE SPECIFIED (NOS)	2/507 (0.4%)
ABDOMINAL PAIN UPPER	2/507 (0.4%)
DIARRHOEA NOS	2/507 (0.4%)
NAUSEA	2/507 (0.4%)
RECTAL HAEMORRHAGE	2/507 (0.4%)
VOMITING NOS	2/507 (0.4%)
ABDOMINAL DISCOMFORT	1/507 (0.2%)
ABDOMINAL DISTENSION	1/507 (0.2%)
CONSTIPATION AGGRAVATED	1/507 (0.2%)
DYSPHAGIA	1/507 (0.2%)
HAEMATEMESIS	1/507 (0.2%)
IRRITABLE BOWEL SYNDROME	1/507 (0.2%)
OESOPHAGITIS NOS	1/507 (0.2%)
SMALL INTESTINAL GANGRENE NOS	1/507 (0.2%)
SMALL INTESTINAL OBSTRUCTION NOS	1/507 (0.2%)
General disorders
CHEST PAIN	2/507 (0.4%)
WEAKNESS	2/507 (0.4%)
PAIN EXACERBATED	1/507 (0.2%)
Hepatobiliary disorders
CHOLELITHIASIS	1/507 (0.2%)
Immune system disorders
DRUG HYPERSENSITIVITY	2/507 (0.4%)
Infections and infestations
URINARY TRACT INFECTION NOS	14/507 (2.8%)
SEPSIS NOS	2/507 (0.4%)
BRONCHOPNEUMONIA NOS	1/507 (0.2%)
CELLULITIS	1/507 (0.2%)
GASTROENTERITIS NOS	1/507 (0.2%)
INFECTION NOS	1/507 (0.2%)
KLEBSIELLA SEPSIS	1/507 (0.2%)
LOWER RESPIRATORY TRACT INFECTION NOS	1/507 (0.2%)
OESOPHAGEAL CANDIDIASIS	1/507 (0.2%)
PNEUMONIA NOS	1/507 (0.2%)
POST PROCEDURAL SITE WOUND INFECTION	1/507 (0.2%)
URINARY TRACT INFECTION BACTERIAL	1/507 (0.2%)
Injury, poisoning and procedural complications
FEMUR FRACTURE	2/507 (0.4%)
ANKLE FRACTURE	1/507 (0.2%)
DEVICE FAILURE	1/507 (0.2%)
FRACTURED PELVIS NOS	1/507 (0.2%)
HIP FRACTURE	1/507 (0.2%)
INCISIONAL HERNIA NOS	1/507 (0.2%)
MEDICAL DEVICE COMPLICATION	1/507 (0.2%)
POST PROCEDURAL URINE LEAK	1/507 (0.2%)
Investigations
LIVER FUNCTION TESTS NOS ABNORMAL	2/507 (0.4%)
BLOOD IN STOOL	1/507 (0.2%)
WEIGHT DECREASED	1/507 (0.2%)
Metabolism and nutrition disorders
HYPOGLYCAEMIA NOS	2/507 (0.4%)
ANOREXIA	1/507 (0.2%)
DEHYDRATION	1/507 (0.2%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/507 (0.2%)
INGUINAL MASS	1/507 (0.2%)
MUSCLE SPASMS	1/507 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG CANCER STAGE UNSPECIFIED (EXCL METASTATIC TUMOURS TO LUNG)	1/507 (0.2%)
MALIGNANT MELANOMA	1/507 (0.2%)
Nervous system disorders
MULTIPLE SCLEROSIS RELAPSE	5/507 (1%)
MULTIPLE SCLEROSIS AGGRAVATED	4/507 (0.8%)
CONVULSIONS NOS	2/507 (0.4%)
DEPRESSED LEVEL OF CONSCIOUSNESS	2/507 (0.4%)
DIZZINESS	2/507 (0.4%)
DYSARTHRIA	2/507 (0.4%)
SOMNOLENCE	2/507 (0.4%)
GRAND MAL CONVULSION	1/507 (0.2%)
HYPOAESTHESIA	1/507 (0.2%)
PARAESTHESIA	1/507 (0.2%)
TREMOR	1/507 (0.2%)
Psychiatric disorders
SUICIDAL IDEATION	2/507 (0.4%)
DELUSIONAL PERCEPTION	1/507 (0.2%)
PARANOIA	1/507 (0.2%)
Renal and urinary disorders
URINARY RETENTION	2/507 (0.4%)
RENAL FAILURE ACUTE ON CHRONIC	1/507 (0.2%)
Respiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATION	2/507 (0.4%)
EPISTAXIS	1/507 (0.2%)
PULMONARY EMBOLISM	1/507 (0.2%)
Skin and subcutaneous tissue disorders
DECUBITUS ULCER	1/507 (0.2%)
URTICARIA NOS	1/507 (0.2%)
Social circumstances
PREGNANCY OF PARTNER	4/507 (0.8%)
Vascular disorders
CIRCULATORY COLLAPSE	1/507 (0.2%)
DEEP VENOUS THROMBOSIS NOS	1/507 (0.2%)
Other (Not Including Serious) Adverse Events
	GW-1000-02
	Affected / at Risk (%)	# Events
Total	477/507 (94.1%)
Gastrointestinal disorders
Nausea	87/507 (17.2%)
Diarrhoea NOS	60/507 (11.8%)
Vomiting NOS	55/507 (10.8%)
Dry Mouth	43/507 (8.5%)
Constipation	27/507 (5.3%)
Glossodynia	26/507 (5.1%)
Oral Pain	24/507 (4.7%)
Dyspepsia	23/507 (4.5%)
Tooth Discolouration	19/507 (3.7%)
General disorders
Fatigue	61/507 (12%)
Weakness	34/507 (6.7%)
Fall	26/507 (5.1%)
Pain Exacerbated	25/507 (4.9%)
Feeling Drunk	25/507 (4.9%)
Application Site Pain	24/507 (4.7%)
Lethargy	18/507 (3.6%)
Oedema Peripheral	17/507 (3.4%)
Influenza Like Illness	16/507 (3.2%)
Malaise	16/507 (3.2%)
Infections and infestations
Urinary Tract Infection NOS	111/507 (21.9%)
Nasopharyngitis	40/507 (7.9%)
Lower Respiratory Tract Infection NOS	30/507 (5.9%)
Influenza	19/507 (3.7%)
Investigations
Gamma-glutamyltransferase Increased	26/507 (5.1%)
Weight Decreased	20/507 (3.9%)
Alanine Aminotransferase Increased	16/507 (3.2%)
Blood Alkaline Phosphatase NOS Increased	13/507 (2.6%)
Musculoskeletal and connective tissue disorders
Muscle Spasms	35/507 (6.9%)
Arthralgia	31/507 (6.1%)
Back Pain	27/507 (5.3%)
Pain in Limb	24/507 (4.7%)
Nervous system disorders
Dizziness	144/507 (28.4%)
Headache Not Otherwise Specified (NOS)	56/507 (11%)
Somnolence	43/507 (8.5%)
Dysgeusia	39/507 (7.7%)
Multiple Sclerosis Aggravated	39/507 (7.7%)
Multiple Sclerosis Relapse	30/507 (5.9%)
Balance Impaired NOS	27/507 (5.3%)
Memory Impairment	18/507 (3.6%)
Disturbance in Attention	17/507 (3.4%)
Mouth Ulceration	28/507 (5.5%)
Psychiatric disorders
Euphoric Mood	22/507 (4.3%)
Depression	20/507 (3.9%)
Depressed Mood	18/507 (3.6%)
Insomnia	18/507 (3.6%)
Anxiety	15/507 (3%)
Respiratory, thoracic and mediastinal disorders
Pharyngitis	26/507 (5.1%)
Cough	18/507 (3.6%)
Skin and subcutaneous tissue disorders
Contusion	16/507 (3.2%)
Rash NOS	16/507 (3.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GW will coordinate the dissemination of data from this study and may solicit input and assistance from the principal investigator. All publications, for example manuscripts, abstracts, oral/slide presentations or book chapters based on this study, must be submitted to GW for corporate review before release.