PainPhase 3TEC-006NCT00725114
Safety & Efficacy Study of Subcutaneous Tetrodotoxin for Moderate to Severe Inadequately Controlled Cancer-related Pain
A Phase 3 study testing Tetrodotoxin in people with Pain and Cancer, run by Wex Pharmaceuticals Inc. at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Tetrodotoxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 165 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2008to Nov 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Male or female 18 years of age and over.
- Inpatient or outpatient with a diagnosis of cancer.
- Stable but inadequately controlled pain with current therapy for at least two weeks.
- Experiencing somatic, visceral and/or neuropathic pain related to cancer.
- 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.
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- Life expectancy of at least 3 months.
- Ability to communicate well with the investigator and to comply with the requirements (restrictions, appointments, and examination schedule) of the entire study.
- Signed informed consent document (prior to any study-related procedures being performed).
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Planned initiation of chemotherapy, radiotherapy, or bisphosphonates within 30 days prior to randomization.
- Use of anaesthetics.
- Use of lidocaine and other types of antiarrhythmic drugs.
- Use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine.
- History of CO2 retention, or SaO2 <80% either on room air or O2 of not greater than 2-4 L/min by nasal cannula.
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- 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.
- 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.
- Known hypersensitivity to puffer fish, tetrodotoxin and/or its derivatives.
- 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.
- 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).
- Females with a positive serum pregnancy test at screening or positive urine pregnancy test on admission to study site.
- 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.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the detailed description
Study Objectives:
Male or female subjects with moderate to severe pain (related to cancer or cancer treatment)inadequately controlled by current therapy:
Primary Objectives:
- To compare the efficacy of subcutaneous tetrodotoxin treatment (TTX) with that of placebo as measured by:
- pain outcome (pain intensity reduction or use of analgesics)
- improvement in quality of life (physical and emotional functioning)
- To compare the safety of subcutaneous tetrodotoxin with that of placebo.
Secondary Objectives:
- To assess the onset of analgesic response of subcutaneous tetrodotoxin.
- To determine the duration of analgesic response associated with subcutaneous tetrodotoxin treatment.
Overall Study Design:
This will be a multicentre, randomized, double-blind, placebo-controlled, parallel-design trial of the efficacy and safety of tetrodotoxin in patients over 18 years of age with stable but inadequately controlled moderate to severe pain associated with cancer. Approximately 15 centers across Canada, New Zealand and Australia are expected to participate. Subcutaneous tetrodotoxin (30 µg b.i.d.) or placebo will be administered to 127 patients per group for four consecutive days.
The study period will be at least three weeks from the start of screening to the end of analgesic response. Patients will be screened for the study and will enter a 4- to 7-day baseline period within 28 days of screening. Following the baseline period, patients will either be admitted to the hospital or be seen at the site's outpatient facility on a daily basis. Patients will be randomized on Day 1 to receive study drug twice daily for four consecutive days. After the treatment period, all patients will be seen again on Days 5, 8, and 15 for further safety and efficacy evaluations, and then every two weeks until their pain returns.
Sample Size:
A total of 254 subjects (127 per treatment arm) will be enrolled in this study. The first interim analysis is planned to adjust the sample size after 60 evaluable subjects are enrolled, completed and data are available for analysis. A second interim analysis is planned after 50% of subjects(110 evaluable subjects) have completed the study and data are available for analysis.
Investigational Product 30 µg TTX (tetrodotoxin injectable) or an equivalent volume of placebo, identical in appearance, injected subcutaneously twice daily for 4 days.
Efficacy Variables:
Efficacy assessments will include global pain intensity, component-specific pain intensity, 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), impressions of change, onset of analgesic response, duration of analgesic response, and time to peak analgesic response.
Safety Variables:
Safety assessments will include adverse event reporting, vital signs, physical and neurological examinations, 12-lead electrocardiogram, clinical laboratory tests.
Data Analysis Method:
Two co-primary endpoints will be analyzed in this study as follows:
Co-primary #1 (composite endpoint): Proportion of responders observed in each treatment arm for the composite endpoint satisfying the following three components:
- a ≥30% decrease in mean pain intensity or a decrease of ≥50% of opioid use from baseline
- a ≥30% improvement of QOL in at least one descriptor of physical functioning
- a ≥30% improvement of QOL in at least one descriptor of emotional functioning
Co-primary #2 (Pain intensity endpoint): Proportion of responders observed in each treatment arm for reduction in pain intensity satisfying the following:
- a ≥30% decrease in mean pain intensity or a decrease of ≥50% of opioid use from baseline
Trends for differences between treatments will be individually tabulated for:
- impact of pain on physical functioning
- impact of pain on emotional functioning
Comparison of the proportion of responders in each treatment group will be made using the Mantel-Haenszel procedure.
Safety as assessed by the analysis of adverse events, abnormal laboratory results, and abnormalities detected by 12-lead electrocardiogram.
- Being tested
- Tetrodotoxin, Placebo
- Keywords
- due, cancer, treatment
- Medical subject headings
- Pain, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TetrodotoxinBiological
Also called TTX
30 µg twice daily for 4 days
PlaceboBiological
2 mL subcutaneous injection twice daily for 4 days
| Study group | Role | What they receive |
|---|---|---|
| Tetrodotoxin | Active comparator | Not described Receives: Biological: Tetrodotoxin |
| Sugar injection | Placebo comparator | Not described Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Dec2010
Secondary outcomes (2)
The period of onset of pain response as reported by responders.
Measured: Dec2010
The number of days a subject meets the definition of pain response.
Measured: Dec2010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2008 (estimated)
- Study startApr 2008
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wex Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Neil Hagen, MD, FRCPC, Study chair, Tom Baker Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00725114
- Sponsor's protocol ID
- TEC-006
- Acronym
- TEC-006
- Status last verified
- Aug 2012
- First submitted
- 28 Jul 2008
- Last updated
- 9 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Hagen NA, Cantin L, Constant J, Haller T, Blaise G, Ong-Lam M, du Souich P, Korz W, Lapointe B. Tetrodotoxin for Moderate to Severe Cancer-Related Pain: A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Trial. Pain Res Manag. 2017;2017:7212713. doi: 10.1155/2017/7212713. Epub 2017 May 7.
PubMed 28555092
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00725114
- Acronym / sponsor ID
- TEC-006 / TEC-006
- Keywords
- due, cancer, treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Wex Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 30 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Objectives:
Male or female subjects with moderate to severe pain (related to cancer or cancer treatment)inadequately controlled by current therapy:
Primary Objectives:
- To compare the efficacy of subcutaneous tetrodotoxin treatment (TTX) with that of placebo as measured by:
- pain outcome (pain intensity reduction or use of analgesics)
- improvement in quality of life (physical and emotional functioning)
- To compare the safety of subcutaneous tetrodotoxin with that of placebo.
Secondary Objectives:
- To assess the onset of analgesic response of subcutaneous tetrodotoxin.
- To determine the duration of analgesic response associated with subcutaneous tetrodotoxin treatment.
Overall Study Design:
This will be a multicentre, randomized, double-blind, placebo-controlled, parallel-design trial of the efficacy and safety of tetrodotoxin in patients over 18 years of age with stable but inadequately controlled moderate to severe pain associated with cancer. Approximately 15 centers across Canada, New Zealand and Australia are expected to participate. Subcutaneous tetrodotoxin (30 µg b.i.d.) or placebo will be administered to 127 patients per group for four consecutive days.
The study period will be at least three weeks from the start of screening to the end of analgesic response. Patients will be screened for the study and will enter a 4- to 7-day baseline period within 28 days of screening. Following the baseline period, patients will either be admitted to the hospital or be seen at the site's outpatient facility on a daily basis. Patients will be randomized on Day 1 to receive study drug twice daily for four consecutive days. After the treatment period, all patients will be seen again on Days 5, 8, and 15 for further safety and efficacy evaluations, and then every two weeks until their pain returns.
Sample Size:
A total of 254 subjects (127 per treatment arm) will be enrolled in this study. The first interim analysis is planned to adjust the sample size after 60 evaluable subjects are enrolled, completed and data are available for analysis. A second interim analysis is planned after 50% of subjects(110 evaluable subjects) have completed the study and data are available for analysis.
Investigational Product 30 µg TTX (tetrodotoxin injectable) or an equivalent volume of placebo, identical in appearance, injected subcutaneously twice daily for 4 days.
Efficacy Variables:
Efficacy assessments will include global pain intensity, component-specific pain intensity, 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), impressions of change, onset of analgesic response, duration of analgesic response, and time to peak analgesic response.
Safety Variables:
Safety assessments will include adverse event reporting, vital signs, physical and neurological examinations, 12-lead electrocardiogram, clinical laboratory tests.
Data Analysis Method:
Two co-primary endpoints will be analyzed in this study as follows:
Co-primary #1 (composite endpoint): Proportion of responders observed in each treatment arm for the composite endpoint satisfying the following three components:
- a ≥30% decrease in mean pain intensity or a decrease of ≥50% of opioid use from baseline
- a ≥30% improvement of QOL in at least one descriptor of physical functioning
- a ≥30% improvement of QOL in at least one descriptor of emotional functioning
Co-primary #2 (Pain intensity endpoint): Proportion of responders observed in each treatment arm for reduction in pain intensity satisfying the following:
- a ≥30% decrease in mean pain intensity or a decrease of ≥50% of opioid use from baseline
Trends for differences between treatments will be individually tabulated for:
- impact of pain on physical functioning
- impact of pain on emotional functioning
Comparison of the proportion of responders in each treatment group will be made using the Mantel-Haenszel procedure.
Safety as assessed by the analysis of adverse events, abnormal laboratory results, and abnormalities detected by 12-lead electrocardiogram.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tetrodotoxin | Active comparator | Biological: Tetrodotoxin |
| Sugar injection | Placebo comparator | Biological: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Male or female 18 years of age and over.
- Inpatient or outpatient with a diagnosis of cancer.
- Stable but inadequately controlled pain with current therapy for at least two weeks.
- Experiencing somatic, visceral and/or neuropathic pain related to cancer.
Key exclusion criteria (14 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Planned initiation of chemotherapy, radiotherapy, or bisphosphonates within 30 days prior to randomization.
- Use of anaesthetics.
- Use of lidocaine and other types of antiarrhythmic drugs.
- Use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TetrodotoxinAlso: TTX30 µg twice daily for 4 days | Biological | Tetrodotoxin |
| Placebo2 mL subcutaneous injection twice daily for 4 days | Biological | Sugar injection |
Primary outcome
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
2 secondary outcomes
The period of onset of pain response as reported by responders.
Time frame: Dec2010
The number of days a subject meets the definition of pain response.
Time frame: Dec2010
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2014.
- Derived from this study: PubMed 28555092Hagen NA, Cantin L, Constant J, Haller T, Blaise G, Ong-Lam M, du Souich P, Korz W, Lapointe B. Tetrodotoxin for Moderate to Severe Cancer-Related Pain: A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Trial. Pain Res Manag. 2017;2017:7212713. doi: 10.1155/2017/7212713. Epub 2017 May 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Neil Hagen, MD, FRCPC study chair
Tom Baker Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tetrodotoxin in people with Pain and Cancer, run by Wex Pharmaceuticals Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00725114, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2014.