Optimisation of Hydromorphone - Naloxone Ratio for the Treatment of Pain

A Confirmatory, Placebo-controlled, Randomised, Double-blind, Single-dummy, Parallel Group, Ratio-finding Study in Constipated Pain Patients to Establish an Optimal Hydromorphone - Naloxone Ratio With an Improved Bowel Function and a Comparable Analgesic Efficacy Compared to Hydromorphone Alone

The purpose of this study is to establish an optimal hydromorphone - naloxone ratio with an improved bowel function for constipated pain patients.

Subjects suffering from cancer or non-cancer pain suffering from constipation cased or aggravated by opioids will be randomised to one of four ratios of hydromorphone PR plus naloxone PR or Hydromorphone PR plus placebo to investigate whether a hydromorphone/naloxone combination will lead to comparable analgesia, with a decrease in constipation, and to investigate the optimal dose ratio of hydromorphone and naloxone.

Inclusion Criteria:

1. Male or female subjects at least 18 years with a history of non-cancer or cancer pain that requires around-the-clock opioid therapy (8, 24 or 48 mg hydromorphone PR per day for the duration of the study).
2. Subjects with constipation caused or aggravated by opioids
3. Subjects must be willing to discontinue their current opioid analgesic routine, and .
4. current laxative regimen

Exclusion Criteria:

1. Chronic or intermittent pain that results from Fibromyalgia or Rheumatoid Arthritis.
2. Subjects presently taking, or who have taken, naloxone <=30 days prior to the start of the Screening Period.
3. Subjects suffering from diarrhoea.
4. Abnormal liver or kidney function.