A prospective, randomized, placebo-controlled, double-blind, cross-over study of the usefulness of sustained-release opioids in the subjective sensation of dyspnoea secondary to advanced disease with no reversible components in opioid naive patients.

Patients will be randomized in a double-blind fashion by the pharmacy’s central randomization service at The Repatriation General Hospital. Each patient will be randomized to receive either a once-daily single 20mg KapanolTM capsule for 4 days followed 4 days of a once-daily single placebo capsule or vice versa. Patients will also receive 1-2 coloxyl with sennaTM tablets daily as prophylactic measure against constipation. Patients will be instructed that they can adjust the quantity and type of laxative according to response and preference. Medications will be dispensed from the central pharmacy according to the blinded randomization scheme. Patients may continue any other ongoing dyspnoea management program that has been prescribed for them prior to entering the study, including oxygen, physical therapy, and non-opioid medications. Since the steady state of five-times Tmax will be reached at 45-60 hours, the maintenance of the study drug for four days will allow sufficient washout time. Analysis will be on days 4 and 8 of the study. Patients will be reviewed by the study investigators at randomisation, at the cross-over point, and at completion of the study (i.e. Days 0, 4, and 8). In addition, patients will be contacted by phone every 2 days when they are not seen by study investigators (i.e. Days 2 and 6) to follow their progress on the study and to monitor for adverse reactions. At the completion of the study or if the patient withdraws early, the patient will revert to their previously prescribed dyspnoea management program as they were receiving prior to beginning of the study.