A Study of Sativex® for Pain Relief Due to Diabetic Neuropathy
Condition: Pain; Diabetic Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies
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: 297.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pain; diabetic neuropathy

Summary:

      The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in
      relieving pain due to Diabetic Neuropathy.
    

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 Type 1 or 2 diabetes mellitus as diagnosed according to the World
             Health Organisation (WHO) criteria.

          -  Diagnosed with neuropathic pain due to distal symmetrical diabetic neuropathy of at
             least six months duration, as defined by a NDS score of at least 4, and in who pain is
             not wholly relieved with their current therapy. The NDS score must be attained from at
             least two different test parameters and not only the ankle jerk reflex.

          -  The last six daily diary 0-10 NRS pain scores before randomisation 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.

          -  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 their assessment of their painful diabetic neuropathy.

          -  Uncontrolled diabetes with HbA1c blood levels of more than 11% at Visit1, Day B1.

          -  Receiving a prohibited medication and were unwilling to stop or comply for the
             duration of the study.

          -  Has used cannabinoid based medications within 60 days of study entry and were
             unwilling to abstain for the duration for the study.

          -  Has used cannabis within 30 days of study entry 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
             IMP.

          -  Postural drop of 20mmHg or more in systolic blood pressure at screening.

          -  Medical history of gastroparesis.

          -  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) 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 randomisation.

          -  Impaired renal function i.e., creatinine clearance is lower than 50 ml/min at Visit 1.

          -  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.

          -  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.