Phase III Clinical Trial of Fentanyl Transdermal Matrix Patch, in the Management of Chronic Intractable Pain- Assessment of Effectiveness, Safety and Pharmacokinetics

An Open Label Study to Confirm the Effectiveness, and Safety of Fentanyl Transdermal Matrix Patch in Japanese Patients With Chronic Intractable Pain Who Has Prior Therapy of Codeine, Morphine Hydrochloride, or Fentanyl Injectable Preparations.

The purpose of this study is to verify the effectiveness, and safety in Japanese patients with chronic intractable pain after 4-week medication of fentanyl transdermal matrix patches containing either 12.5 mcg/hr, 25 mcg/hr, 50 mcg/hr, 75 mcg/hr, or 100 mcg/hr, who have been switched from existing formulations, such as codeine, morphine hydrochloride, or fentanyl injectable. Furthermore, the safety and effectiveness of long term treatment such as 48 weeks are to be assessed, if possible.

Fentanyl transdermal matrix patch is a narcotic analgesic agent. Compared with the existing reservoir-type Durotep® Patch, fentanyl transdermal matrix patch is not liable to leakage of drug solution and does not contain alcohol, which becomes a cause of skin irritation. Also this new formulation has become available in a smaller dose of 12.5mg/hr while the smallest Durotep® Patch is 25mg/hr. While Durotep® Patch is currently indicated only for cancer pain in Japan, this clinical trial was planned to assess effectiveness, and safety of fentanyl transdermal matrix patch in Japanese patients with chronic intractable pain receiving codeine, morphine hydrochloride, or fentanyl injectable formulations. After pre-treatment period for seven to fourteen days for evaluating the eligibility of the patients for the study, patients will be treated for 4 weeks as Treatment period 1 and 48 weeks as Treatment period 2 followed by 3-day post-treatment observation period. One patch can be used for 72 hours, which is the same as the existing Patch. Starting from the first day of treatment, fentanyl will be applied to the chest, the upper arm or other appropriate site, which will be replaced with a new patch every three days (ca. 72 hr). Starting dose should be between 12.5 mcg/hr and 75 mcg/hr, depending on the prior opioid dose.

Inclusion Criteria:

• Patients with chronic intractable pain receiving any of the following treatments :(1)Codeine phosphate, (2)Morphine hydrochloride preparations equivalent to less than 315 mg/day of oral morphine, (3)Fentanyl citrate injectable solution equivalent to less than 0.3 mg/day
• Patients with chronic intractable pain in whom lesions causative of pain cannot be removed or treated, or in whom pain has been persisting for at least 12 weeks despite of the existing medication
• Patients may be hospitalized during application of the initial transdermal dose of fentanyl transdermal matrix patches (patients may be ambulatory when the study starts).

Exclusion Criteria:

• Patients with respiratory dysfunction such as chronic pulmonary disease
• Patients with asthma
• Patients with bradyarrhythmia
• Patients with concurrent liver and/or kidney dysfunction according to the latest laboratory test values within 14 days before the start of the pre-treatment observation period
• Patients with organic brain disorder such as elevated intracranial pressure, disturbance of consciousness/coma, or brain tumor
• Patients with any psychoneurologic complication and judged incapable of self assessment
• Patients with or with a history of drug dependency or narcotic abuse
• Patients with a history of hypersensitivity to fentanyl or any other opioid analgesic