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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wex Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT00726011
First received: July 28, 2008
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Pain
Cancer
Biological: Tetrodotoxin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicentre, Open-label, Long-term Efficacy and Safety Continuation Study of Subcutaneous Tetrodotoxin (TTX) for Moderate to Severe Cancer-related Pain

Resource links provided by NLM:


Further study details as provided by Wex Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Efficacy: long-term efficacy of tetrodotoxin (TTX) in reducing pain and improving quality of life. Safety: long-term safety and tolerability of s.c. TTX [ Time Frame: Repeat treatment for patients with meaningful analgesic response ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • For each Treatment Cycle: the total number of days a subject meets the definition of pain response. [ Time Frame: Repeat treatment for subjects with meaningful analgesic response ] [ Designated as safety issue: No ]

Enrollment: 113
Study Start Date: July 2008
Study Completion Date: July 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tetrodotoxin
There is only one arm; active treatment with TTX
Biological: Tetrodotoxin
30 µg twice daily for 4 days; repeated every two weeks as long as there is a meaningful analgesic response
Other Name: TTX

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All patients who participated in the TEC-006 study (tetrodotoxin and placebo-treated) will be eligible for inclusion in this study provided they wish to continue to receive treatment and meet the inclusion and exclusion criteria.

NOTE: The blinded treatment assignment of patients in the TEC-006 will not be revealed to either the investigator or the patient. Patients will not be aware which treatment they received in the TEC-006 study. All patients will receive tetrodotoxin treatment in the TEC-006OL study.

A patient will be eligible or continue to be eligible for inclusion in this study (First Treatment Cycle and subsequent Treatment Cycles) only if all of the following criteria apply:

  1. Male or female 18 years of age and over
  2. In-patients or out-patients with a diagnosis of cancer
  3. Patients must be experiencing somatic, visceral and/or neuropathic pain related to cancer.
  4. Compliant to the requirements of the TEC-006 Protocol.
  5. Inadequately controlled pain: Pain intensity described as 'moderate', 'severe' or 'excruciating', as assessed by the VRS during the screening/baseline period of the First Treatment Cycle, and a baseline pain intensity score of ≥4 as assessed by NRS (worst, average, or component-specific pain).
  6. Meet the Responder or Clinical Responder definition for repeat cycle treatment (cycle #2 to cycle #4)
  7. Life expectancy of > 3 months.
  8. Ability to communicate well with the Investigator and to comply with the requirements of the entire study.

8. Willingness to give written informed consent (prior to any study-related procedures being performed) and to be able to adhere to the study restrictions, appointments and examination schedule.

Exclusion Criteria:

A patient will not be eligible for inclusion in this study if any of the following criteria apply:

  1. Planned initiation of chemotherapy, radiotherapy or bisphosphonates within 30 days prior to enrolment.
  2. Known renal disease.
  3. If it has been more than 14 days since their TEC_006 End of Study Visit or their pain returned to baseline since their last tetrodotoxin treatment cycle (for repeat cycle).
  4. Patient has previously completed 4 cycles of tetrodotoxin
  5. If it has been more than 6 months since patient signed consent to participate in the TEC-006 OL study.
  6. Use of anaesthetics.
  7. Use of lidocaine, and other types of antiarrhythmic drugs.
  8. Use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine.
  9. History of CO2 retention, or SaO2 <80% either on room air or O2 of not greater than 2-4 L/min by nasal cannula.
  10. Second or third degree heart block or prolonged QTc interval (corrected for rate) on screening ECG (confirmed > 450 msec on repeated occasion) or any other active cardiac arrhythmia or abnormality that would constitute a clinical risk.
  11. Coagulation or bleeding defects if in the opinion of the Investigator this represents a risk to the subject considering the subcutaneous (s.c.) route of administration.
  12. Known hypersensitivity to puffer fish, tetrodotoxin and/or its derivatives.
  13. Received an investigational agent other than tetrodotoxin within 30 days prior to screening or who is scheduled to receive an investigational drug other than tetrodotoxin during the course of the study.
  14. Females who are lactating or at risk of pregnancy (i.e., sexually active with fertile males and not using an adequate form of birth control).
  15. Females with a positive pregnancy test at screening or on admission to study site.
  16. Any other condition that, in the opinion of the investigators, is likely to interfere with the successful collection of the measures required for the study or poses a risk to the patient.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00726011

Locations
Canada, British Columbia
WEX Pharmaceuticals Inc.
Vancouver, British Columbia, Canada, V6C 1G8
Sponsors and Collaborators
Wex Pharmaceuticals Inc.
Investigators
Study Chair: Dr. Neil Hagen, MD, FRCPC Tom Baker Cancer Centre
  More Information

No publications provided

Responsible Party: Wex Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00726011     History of Changes
Other Study ID Numbers: TEC-006OL
Study First Received: July 28, 2008
Last Updated: October 22, 2012
Health Authority: Canada: Health Canada

Keywords provided by Wex Pharmaceuticals Inc.:
due
cancer treatment

Additional relevant MeSH terms:
Tetrodotoxin
Anesthetics
Anesthetics, Local
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Sodium Channel Blockers
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014