Clinical trial NCT00710554: A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
Official title: A Double Blind, Randomized, Placebo Controlled, Parallel Group Study of Sativex® in the Treatment of Subjects With Peripheral Neuropathic Pain, Associated With Allodynia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Peripheral Neuropathy
Keywords: Pain
Peripheral Neuropathy
Allodynia
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-07-04
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving peripheral neuropathic pain associated with allodynia.

Detailed description: This was a 15 week (one week baseline and fourteen weeks treatment period), multicentre, double blind, randomised, placebo controlled, parallel group study to evaluate the efficacy of Sativex® in subjects with PNP, associated with allodynia. Subjects were screened to determine eligibility and completed a seven-day baseline period. Subjects then returned to the centre for assessment, randomisation and dose introduction. Visits occurred at the end of weeks two, six, ten and at the end of the study (treatment week 14) or earlier if they withdrew. A follow up visit occurred 28 days after completion or withdrawal. Subjects in this study were given the opportunity to be enrolled in an open label extension study.

Eligibility criteria: Inclusion Criteria:

* Willing and able to give informed consent.
* Male or female, aged 18 years or above.
* Ability (in the investigators opinion) and willingness to comply with all study requirements.
* Diagnosed with PNP of at least six months duration and in who pain is not wholly relieved with their current therapy.
* Presence of mechanical allodynia within the territory of the affected nerve(s) which has been confirmed by either a positive response to stroking the allodynic area with a SENSELABTM Brush 05 or to force applied by a 5.07 gram Semmes-Weinstein monofilament.
* Had at least one of the following underlying conditions, which caused their peripheral neuropathic pain; post herpetic neuralgia, peripheral neuropathy, focal nerve lesion, radiculopathy or Complex Regional Pain Syndrome (CRPS) type 2.
* The daily diary 0-10 NRS pain scores on days B2 - B7 of the baseline period were completed and summed to at least 24.
* Stable dose of regular pain medication and non-pharmacological therapies (including TENS) for at least 14 days prior to the screening visit and willingness for these to be maintained throughout the study. Where subjects were taking a medication containing paracetamol further instructions were provided, refer to Section 9.4.7.
* In the opinion of the investigator the subject has received or was currently receiving the appropriate PNP treatments for their condition.
* 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:

* Concomitant pain thought by the investigator to be of a nature or severity to interfere with the subject's assessment of their PNP.
* Receiving a prohibited medication and were unwilling to stop or comply for the duration of the study.
* Had CRPS type 1, cancer related neuropathic pain or neuropathic pain resulted from diabetes mellitus.
* Has used either cannabis (either for recreational or medical purposes) or cannabis based medications within the last year and were unwilling to abstain for the duration for the study.
* 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 5 minutes prior to randomisation.
* 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 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.
* 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 exam, 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.
* Intention to travel internationally during the study.
* Previous randomisation into this study.

Primary outcomes:
measure: Change From Baseline in Mean Peripheral Neuropathic Pain on a 0-10 Numerical Rating Scale (NRS) Score at the End of Treatment (15 Weeks)
timeFrame: Day 7 to Day 98
Secondary outcomes:
measure: Change From Baseline in Neuropathic Pain Scale Score at the End of Treatment (15 Weeks)
timeFrame: Day 7 to Day 98
measure: Change From Baseline in Sleep Quality 0-10 Numerical Rating Scale Scores at the End of Treatment (15 Weeks)
timeFrame: Day 7 to Day 98
measure: Change in Baseline Mean Dynamic Allodynia Test Score at the End of Treatment (15 Weeks)
timeFrame: Day 7 and Day 98
measure: Change in Baseline Mean Punctate Allodynia Test Scores at the End of Treatment (15 Weeks)
timeFrame: Day 7 and Day 98
measure: Subject Global Impression of Change
timeFrame: Day 98
measure: Change From Baseline in Brief Pain Inventory (Short Form) Scores at the End of Treatment
timeFrame: Day 7 and Day 98
measure: Change From Baseline in Quality of Life EuroQol 5-D (Health Status Index) Score at the End of Treatment (15 Weeks)
timeFrame: Day 7 and Day 98
measure: Change From Baseline in Quality of Life EuroQol 5-D (Health Status Visual Analogue Scale) Score at the End of Treatment (15 Weeks)
timeFrame: Day 7 and Day 98
measure: Change From Baseline in the Use of Rescue Analgesia at the End Treatment (15 Weeks)
timeFrame: Days 0-7 and Days 92-98
measure: Incidence of Adverse Events as a Measure of Subject's Safety.
timeFrame: 19 weeks
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Pain Clinic Office, Gartnavel General Hospital,
state: West Lothain
Study officials:
affiliation: Pain Clinic Office
name: Mick Serpell, MB ChB, FRCA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Serpell M, Ratcliffe S, Hovorka J, Schofield M, Taylor L, Lauder H, Ehler E. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain. 2014 Aug;18(7):999-1012. doi: 10.1002/j.1532-2149.2013.00445.x. Epub 2014 Jan 13.