A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.

A Multicentre, Open Label, Follow on Study to Assess the Maintenance of Effect, Tolerance and Safety of Sativex® in the Treatment of Subjects With Neuropathic Pain. This Will be Followed by a Randomised-withdrawal Phase (Part B) for a Subset of Patients.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00713323

Enrollment

380

Registered

2008-07-11

Start date

2005-10-31

Completion date

2007-06-30

Last updated

2023-05-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain, Peripheral Neuropathy

Keywords

Pain, Peripheral Neuropathy

Brief summary

The purpose of this study is to assess the safety and tolerability of long term therapy with Sativex® in relieving neuropathic pain.

Detailed description

This was a 38 week, multicentre, open label (Part A) follow-on study to evaluate, the maintenance of effect of, the development of tolerance through exposure to, and safety of, Sativex® in the treatment of subjects with neuropathic pain. The study provided continued availability of Sativex® to subjects who completed the preceding double-blind neuropathic pain studies. Consenting, eligible subjects who had participated in previous GW Pharma Ltd (GW) randomised, placebo-controlled clinical studies entered the study (Visit 1, Day 0) and commenced dosing. Study visits took place at Week 2 (Visit 2, Day 14), Week 14 (Visit 3, Day 98), and Week 26 (Visit 4, Day 182). Subjects returned to the centre for an end of treatment visit at week 38 (Visit 5, Day 266). All subjects received Sativex®. This was followed by a five week randomised-withdrawal phase (Part B) for a subset of subjects. An end of study visit took place 28 days after Visit 5 (or 5b or 5c) or withdrawal from the study.

Interventions

DRUGSativex®

containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Had participated in a GW clinical study to investigate the effects of Sativex® on peripheral neuropathic pain and had completed the study. This must have been within the last seven days * Had complied with all of the study requirements in the preceding GW parent RCTs, including the completion of diary cards and study questionnaires * Had shown tolerability to the study medication in a preceding GW study * Was expected, in the opinion of the investigator, to gain clinical benefit from receiving Sativex® therapy * Ability (in the investigators opinion) and willingness to comply with all study requirements, including the completion of diary cards and study questionnaires * Agreement for the responsible authorities (as applicable in individual countries), their primary care physician, and their consultant, if appropriate, to be notified of their participation in the study.

Exclusion criteria

* History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition * Known or suspected history of alcohol or substance abuse * History of epilepsy or recurrent seizures * Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication Evidence of cardiomyopathy * Experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction * QT interval; of \> 450 ms (males) or \> 470 ms (females) at Visit 1 * Secondary or tertiary AV block or sinus bradycardia (HR \<50bpm unless physiological) or sinus tachycardia (HR\>110bpm) at Visit 1 * Diastolic blood pressure of \<50 mmHg or \>105 mmHg in a sitting position at rest for five minutes prior to measurement at Visit 1 * Impaired renal function i.e., creatinine clearance is lower than 50ml/min at Visit 1 and is indicative of renal impairment * Significantly impaired hepatic function, at Visit 1, in the Investigator's opinion * Female subjects of child bearing potential and male subjects whose partner was of child bearing potential, unless they were willing to ensure that they or their partner used effective contraception during the study and for three months thereafter * If female, were pregnant or lactating, or were planning pregnancy during the course of the study and for three months thereafter * Received an IMP within the 12 weeks before Visit 1 (except the prerequisite study medication from the GW parent RCTs) * 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 had any abnormalities that, in the opinion of the investigator, would prevent the subject from safely participating in the study. * Intention to donate blood during the study * Previous randomisation into this study

Design outcomes

Primary

Measure	Time frame	Description
Change From Parent Study Baseline in Mean Pain 0-10 Numerical Rating Scale (NRS) Score During the Last 4 Weeks of Open-label Treatment	38 weeks	The average pain NRS was complete at the same time each day, i.e. bedtime in the evening. The patient was asked on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. A negative value indicates an improvement in pain score from baseline.

Secondary

Measure	Time frame	Description
Change From Parent Study Baseline in Mean Sleep Quality 0-10 NRS Score at the End of Open-label Treatment (Week 38)	38 weeks	The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night? where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Subject Global Impression of Change	week 38	A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain since entry into the study using the scale below' with the markers very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse. At Visit 2 (Baseline) patients wrote a brief description of their pain which was used at Week 5 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Change From Parent Study Baseline in Mean EuroQol-5D Weighted Health State Index Score at the End of Open-label Treatment	38 weeks	The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.The weighted health state index used the same VAS as above but was calculated for each assessment without imputation to account for missing values i.e., if one or more individual items was missing then the whole index was missing.
Change From Parent Study Baseline in Mean Neuropathic Pain Scale (NPS) Score at End of Open-label Treatment (Week 38)	38 weeks	The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Incidence of Adverse Events as a Measure of Subject Safety	42 weeks	The number of subjects who reported an adverse event during Part A of the study is presented (including the follow-up period of 28 days following cessation of opel-label treatment).
Change From Parent Study Baseline in Mean Intoxication 0-10 Numerical Rating Scale Score at the End of Open-label Treatment (38 Weeks)	38 weeks	The patient was asked on a scale of '0 to 10' please indicate the average level of your intoxication due to medications over the last 24 hours (0=no intoxication and 10=extreme toxication). A negative value indicates an improvement in pain score from baseline.
Change From Parent Study Baseline in Mean EuroQol-5D Self-rated Health Status Visual Analogue Scale Score at the End of Open-label Treatment	38 weeks	The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
Sativex Subjects received Sativex delivered in 100 μl actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations in 24 hours (THC 65 mg:CBD 60 mg).	380
Total	380

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	75
Overall Study	Lack of Efficacy	36
Overall Study	Lost to Follow-up	11
Overall Study	Low creatine clearance at screening	1
Overall Study	Non-compliance	1
Overall Study	Pain free	1
Overall Study	Pain resolved	1
Overall Study	Subject travelling to Dominica Republic	1
Overall Study	Subject travelling to USA	1
Overall Study	Surgery cured allodynic pain	1
Overall Study	Treatment that may interact with Sativex	1
Overall Study	Withdrawal by Subject	15
Overall Study	Withdrawn due to exclusion criteria 11	1

Baseline characteristics

Characteristic	Sativex
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	93 Participants
Age, Categorical Between 18 and 65 years	287 Participants
Age, Continuous	57.8 years STANDARD_DEVIATION 12.03
Region of Enrollment Belgium	9 participants
Region of Enrollment Canada	5 participants
Region of Enrollment Czech Republic	94 participants
Region of Enrollment Romania	50 participants
Region of Enrollment United Kingdom	222 participants
Sex: Female, Male Female	180 Participants
Sex: Female, Male Male	200 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	295 / 380
serious Total, serious adverse events	40 / 380

Outcome results

Primary

Change From Parent Study Baseline in Mean Pain 0-10 Numerical Rating Scale (NRS) Score During the Last 4 Weeks of Open-label Treatment

The average pain NRS was complete at the same time each day, i.e. bedtime in the evening. The patient was asked on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. A negative value indicates an improvement in pain score from baseline.

Time frame: 38 weeks