Safety & Efficacy Study of Subcutaneous Tetrodotoxin for Moderate to Severe Inadequately Controlled Cancer-related Pain (TEC-006)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Wex Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT00725114
First received: July 28, 2008
Last updated: August 8, 2012
Last verified: August 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-006) is designed to 1) demonstrate in a double-blind, placebo-controlled trial that the subcutaneous 30 μg b.i.d. dose of TTX for 4 days is effective in reducing pain outcome and improving quality of life; 2) characterize the onset and duration of analgesia, and 3) demonstrate that TTX is well tolerated in patients with inadequately controlled cancer-related pain.


Condition Intervention Phase
Pain
Cancer
Biological: Tetrodotoxin
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre , Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of the Efficacy and Safety of Subcutaneous Tetrodotoxin (TTX) for Moderate to Severe Inadequately Controlled Cancer-related Pain

Resource links provided by NLM:


Further study details as provided by Wex Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Efficacy: Composite-endpoint will be an evaluation that combines pain outcome and quality of life. Pain intensity will be used a co-primary endpoint. Safety as assessed by the analysis of AEs, 12-lead ECG, and abnormal lab values. [ Time Frame: Dec2010 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The period of onset of pain response as reported by responders. [ Time Frame: Dec2010 ] [ Designated as safety issue: No ]
  • The number of days a subject meets the definition of pain response. [ Time Frame: Dec2010 ] [ Designated as safety issue: No ]

Estimated Enrollment: 254
Study Start Date: April 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tetrodotoxin Biological: Tetrodotoxin
30 µg twice daily for 4 days
Other Name: TTX
Placebo Comparator: Sugar injection Biological: Placebo
2 mL subcutaneous injection twice daily for 4 days
Other Name: Placebo

  Show Detailed Description

  Eligibility

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

Inclusion criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

  1. Male or female 18 years of age and over.
  2. Inpatient or outpatient with a diagnosis of cancer.
  3. Stable but inadequately controlled pain with current therapy for at least two weeks.
  4. Experiencing somatic, visceral and/or neuropathic pain related to cancer.
  5. Baseline pain intensity, as assessed by Question #3 of the Brief Pain Inventory (BPI) that meets the definition of "moderate" (score of 4-5) or "severe" (score of 6-10) pain.
  6. Life expectancy of at least 3 months.
  7. Ability to communicate well with the investigator and to comply with the requirements (restrictions, appointments, and examination schedule) of the entire study.
  8. Signed informed consent document (prior to any study-related procedures being performed).

Exclusion criteria

A subject 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 randomization.
  2. Use of anaesthetics.
  3. Use of lidocaine and other types of antiarrhythmic drugs.
  4. Use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine.
  5. History of CO2 retention, or SaO2 <80% either on room air or O2 of not greater than 2-4 L/min by nasal cannula.
  6. 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 could constitute a clinical risk.
  7. 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.
  8. Known hypersensitivity to puffer fish, tetrodotoxin and/or its derivatives.
  9. Use of an investigational agent within 30 days prior to screening or is scheduled to receive an investigational drug other than tetrodotoxin during the course of the study.
  10. 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).
  11. Females with a positive serum pregnancy test at screening or positive urine pregnancy test on admission to study site.
  12. 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.
  13. Men with glomerular filtration rate (GRF) less than 60 mL/min/1.73 m2 and women with GFR less than 50 mL/min/1.73 m2
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00725114

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: NCT00725114     History of Changes
Other Study ID Numbers: TEC-006
Study First Received: July 28, 2008
Last Updated: August 8, 2012
Health Authority: Canada: Health Canada

Keywords provided by Wex Pharmaceuticals Inc.:
due
cancer
treatment

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

ClinicalTrials.gov processed this record on April 23, 2014