Tetrodotoxin Open-label Efficacy and Safety Continuation Study — TEC-006OL  

Pain Clinical Trial

Official title: A Multicentre, Open-label, Long-term Efficacy and Safety Continuation Study of Subcutaneous Tetrodotoxin (TTX) for Moderate to Severe Cancer-related Pain

Status Completed

Clinical Trial Summary

Different pathophysiologic mechanisms are responsible for the development of chronic pain disorders. Pain pathways are triggered in part by ectopic discharges of voltage-sensitive sodium channels, which are in abundance in both the peripheral and the central nervous systems. Tetrodotoxin (TTX) is a selective blocker of Na+ channels and causes analgesia either by decreasing the propagation of action potentials by Na+ channels and/or by blocking of ectopic discharges associated with chronic pain. TTX is extracted from the puffer fish (fugu). Results from animal pharmacology studies revealed that TTX is a more potent analgesic than standard analgesic agents such as aspirin, morphine or meperidine.

At present, the management of severe cancer pain generally includes the use of opiates. This can often result in undesirable side effects, and treatment with this type of medication is not always effective. Because currently available pain-relieving therapy is unsatisfactory for many patients, there is a need for new therapeutic approaches for the management of moderate or severe cancer pain.

Recent studies indicate that intramuscular (into a muscle) or subcutaneous (under the skin) injections of tetrodotoxin (TTX) may reduce pain in cancer patients who did not respond to standard therapies.

The current proposed study (TEC-006OL) is designed to provide the option for all patients who participated in the TEC-006 study (both tetrodotoxin and placebo-treated) to receive or continue to receive tetrodotoxin treatment.

Clinical Trial Description

Study Objectives: In cancer patients with moderate to severe pain who participated in the TEC-006 study:

Primary Objectives:

• To assess the long-term efficacy of subcutaneous tetrodotoxin (TTX) treatment in reducing the pain outcome and improving the quality of life (physical and emotional functioning).

• To assess the long-term safety and tolerability of subcutaneous tetrodotoxin (TTX).

Secondary Objective:

• To assess the duration of analgesia following repeated cycles of tetrodotoxin (TTX) treatment.

Overall Study Design:

This will be a multicentre, open-label, continuation trial of the efficacy and safety of tetrodotoxin in patients with inadequately controlled moderate to severe pain associated with cancer. All patients who participated in the TEC-006 study (tetrodotoxin and placebo-treated), who would like to continue with tetrodotoxin treatment and meet the inclusion/exclusion criteria, are eligible to receive the First Treatment Cycle for this continuation study.

The study will be conducted at all centres participating in the TEC-006 study. Patients may receive repeated cycles of treatment with tetrodotoxin. Each Treatment Cycle will consist of 4 days of treatment with 30 μg b.i.d. of tetrodotoxin injected subcutaneously. Each Treatment Cycle will last from the start of treatment to the end of the analgesic response. All patients completing the first Treatment Cycle in this protocol must meet the criteria of the Responder (First TEC-006OL Treatment Cycle) definition in order to be eligible for a second Treatment Cycle. Patient eligibility for all subsequent Treatment Cycles will be determined using the eligibility criteria for a Repeated Treatment Cycle.

Sample Size:

Up to 120 patients.

Investigational Product:

30ug TTX(Tetrodotoxin injectable) injected subcutaneously twice daily for 4 days.

Efficacy Variables:

Worst pain in last 24 hours, average pain in last 24 hours, and/or component-specific pain intensity in last 24 hours, ATC and breakthrough analgesic use, impact of pain on physical functioning (general activity, walking ability, or normal work), and emotional functioning (mood, relations with other people, or enjoyment of life).

Safety Variables:

Safety assessments will include adverse event reporting, vitals signs, physical and neurological examinations, 12-lead electrocardiogram, clinical laboratory tests.

Data Analysis Method:

An initial analysis of results of the TEC-006OL study will be completed in parallel with the TEC-006 study. Further periodic analyses will be completed every 6 months until the study is closed.

All efficacy and safety analyses will be performed for subjects that are dosed at least once in protocol TEC-006OL. All analyses performed will be descriptive. No statistics involving hypothesis testing will be performed. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Pain

• NCT number: NCT00726011
• Study type: Interventional
• Source: Wex Pharmaceuticals Inc.
• Status: Completed
• Phase: Phase 3
• Start date: July 2008
• Completion date: July 2012