A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
Condition: Pain; Peripheral Neuropathy
MeSH terms: Neuralgia; Peripheral Nervous System Diseases; Hyperalgesia
Intervention: Sativex; Placebo
Intervention description: 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; containing peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient.
Intervention MeSH terms: Nabiximols
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 246.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pain; Peripheral Neuropathy; Allodynia

Summary:

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

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.