A double blind, randomized, placebo controlled, parallel group dose range exploration study of Sativex® in relieving pain in patients with advanced cancer, who experience inadequate analgesia during optimized chronic opioid therapy.

• Conditions: Pain in patients with advanced cancer, who experience inadequate analgesia during optimized chronic opioid therapy.

• Registration Number: EUCTR2007-005225-30-DE
• Lead Sponsor: GW Pharma Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02-20
• Last Update Posted: 14 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 336

Inclusion Criteria

Inclusion:

• The patient has advanced active cancer for which there is no known curative therapy.
• The patient is able (in the investigators opinion) and willing to comply with all study requirements.
• The patient has a clinical diagnosis of cancer related pain, which is not wholly alleviated with their current opioid treatment.
• The patient is receiving a sustained release (SR) fixed dose of opioid therapy (excluding Methadone). N.B. The opiate therapy must be Step III according to the WHO analgesic ladder.
• If the response to either of the two criteria below is yes, then the
patient is eligible for the trial.
1. The patient is currently receiving a SR fixed dose opioid at a daily dose
equivalent to less than 90mg of morphine, and has
experienced opioid-related side effects which preclude further increases in
daily opioid dose.
2. The patient is currently receiving a SR fixed dose opioid at a daily dose
equivalent to at least 90mg of morphine, and is not expected
to gain additional therapeutic benefit by further increasing the dose of the
SR opioid therapy.
• All of the following criteria must be met on the same three consecutive days during the baseline period in order to be eligible for randomization:
1. The patient is receiving no more than an average of 4 doses of opioid break-through analgesia (IR) per day. Please note that patients are permitted to use more than one type of break-through opioid analgesia (IR) in the study.
N.B., The opioid break-through analgesia must be Step III according to
the WHO analgesic ladder.
2. The patient has not altered their SR fixed dose opioid therapy.
3. The level of pain is =4 and =8 on an 11-point NRS for three consecutive days, when the patient is asked the following question:
On a scale of ‘0 to 10’, please rate your pain by indicating the number that best describes your pain on average in the last 24 hours” where:
0 = no pain” and 10 = Pain as bad as you can imagine”
4. The 11-point NRS does not change by more than two points over the three consecutive days (i.e., no more than two points between the highest and lowest scores).
5. The patient is not experiencing intolerable side effects.
• The patient is willing to continue to take their regular daily baseline opioid regimen (SR) at the same dose, throughout the duration of study.
• The patient has satisfactorily completed the IVRS.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion

• The patient should be excluded from entering study if they have received or are due to receive during the study period; chemotherapy, hormone therapy or radiotherapy, which, in the opinion of the investigator will affect their pain.
• The patient is currently receiving a prohibited medication and unwilling to stop or comply for the duration of the study.
• The patient is currently using or has used cannabis or cannabinoid based medications or Acomplia [Rimonabant] within 30 days of study entry and unwilling to abstain for the duration of the study.
• Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
• Any known or suspected history of a diagnosed dependence disorder, current heavy alcohol consumption, current use of an illicit drug or current non prescribed use of any prescription drug.
• The patient has poorly controlled epilepsy or recurrent seizures (i.e. at least one year since last seizure).
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IP.
• The patient has experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the patient at risk of a clinically relevant arrhythmia or myocardial infarction.
• The patient has a QT interval of > 450 ms (males) or > 470 ms (females) at Visit 1.
• The patient has a secondary or tertiary atrioventricular (AV) block or sinus bradycardia (HR <50bpm unless physiological) or sinus tachycardia (HR>110bpm) at Visit 1.
• The patient has a diastolic blood pressure of <50 mmHg or >105 mmHg (when measured in a sitting position at rest for 5 minutes) prior to randomization.
• In the opinion of the Investigator, the patient has impaired renal function, which could put the patient at risk during participation in the trial.
• The patient has significantly impaired hepatic function at Visit 1 (ALT >5X Upper limit of normal (ULN) or bilirubin > 2X ULN).
• Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for three months thereafter.
• Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
• Patients who have received an IP within the 12 weeks before Visit 1.
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the result of the study, or the patient’s ability to participate in the study.
• Following a physical exam, the patient has any abnormalities that, in the
opinion of the investigator, would prevent them from safely participating in the study.
• Unwilling to abstain from donation of blood during the study.
• Travel outside the country of residence planned during the study.
• Patients previously randomized into this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To evaluate the efficacy of Sativex compared with placebo on:<br><br>• Secondary measures of pain relief<br>• Sleep Disruption<br>• Patient Assessment of Constipation Quality of Life (PAC-QoL)<br>• Patient global impression of change (PGIC)<br>• Montgomery Asberg Depression Rating Scale (MADRS)<br>• Addiction Research Center Inventory (ARCI)<br><br>To assess the safety and tolerability of Sativex®.;Primary end point(s): The primary endpoint is the patient 30% pain response status, where a response is defined as a 30% or greater reduction in the IVRS 11-point Numeric Rating Scale pain score (average pain) during the last three days of week 5 compared with the 3 day baseline period.;Main Objective: To determine the effective dose range and to demonstrate a non-effective dose range of Sativex in patients with advanced cancer, who experience inadequate analgesia during optimized chronic opioid therapy.