A Study of Sativex® for Pain Relief Due to Diabetic Neuropathy

A Double Blind, Randomized, Placebo Controlled, Parallel Group Study of Sativex in the Treatment of Subjects With Pain Due to Diabetic Neuropathy

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

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 pain due to diabetic neuropathy. 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.

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.