Clinical trial NCT00713323: A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Peripheral Neuropathy
Keywords: Pain
Peripheral Neuropathy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-07-11
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Parent Study Baseline in Mean Pain 0-10 Numerical Rating Scale (NRS) Score During the Last 4 Weeks of Open-label Treatment
timeFrame: 38 weeks
Secondary outcomes:
measure: Change From Parent Study Baseline in Mean Neuropathic Pain Scale (NPS) Score at End of Open-label Treatment (Week 38)
timeFrame: 38 weeks
measure: Change From Parent Study Baseline in Mean Sleep Quality 0-10 NRS Score at the End of Open-label Treatment (Week 38)
timeFrame: 38 weeks
measure: Subject Global Impression of Change
timeFrame: week 38
measure: Change From Parent Study Baseline in Mean EuroQol-5D Weighted Health State Index Score at the End of Open-label Treatment
timeFrame: 38 weeks
measure: Change From Parent Study Baseline in Mean EuroQol-5D Self-rated Health Status Visual Analogue Scale Score at the End of Open-label Treatment
timeFrame: 38 weeks
measure: Incidence of Adverse Events as a Measure of Subject Safety
timeFrame: 42 weeks
measure: Change From Parent Study Baseline in Mean Intoxication 0-10 Numerical Rating Scale Score at the End of Open-label Treatment (38 Weeks)
timeFrame: 38 weeks
Other outcomes:
Locations:
city: Solihull
country: United Kingdom
facility: Pain Management Research, Clinical Trials Unit, Netherwood House, Solihull Hospital
state: West Midlands
Study officials:
affiliation: Pain Management Research, Clinical Trials Unit, Netherwood House, Solihull Hospital
name: Barbara Hoggart, MBBS, FRCA
role: PRINCIPAL_INVESTIGATOR
References: