Overview
A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain
Status:
Recruiting
Recruiting
Trial end date:
2025-02-01
2025-02-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
To be eligible for the trial, subjects must have ongoing moderate to severe neuropathic pain related to a prior course of platinum and/or taxane chemotherapy and have no clinical evidence of actively progressive disease. The trial period will comprise a Screening Period (up to 35 Days), a two-week period for the determinations of Baseline pain followed by randomization and 4-day treatment, followed by a 12-week follow up period (12 weeks total after initial treatment), and an End-of-Trial/Follow-up visit, which will occur at Week 13. This is a study to research the effects of the study drug on neuropathic pain compared placebo.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Wex Pharmaceuticals Inc.Treatments:
Tetrodotoxin
Criteria
Inclusion Criteria:• Male or female subjects aged ≥21 years.
o Subjects and their partners using an acceptable method of birth control. Female subjects
of child-bearing potential (see below) must have a negative pregnancy test (urine or serum)
at the screening visit and must agree to use adequate birth control from the time of
signature of the informed consent form up until 30 days following the end of the Treatment
Period.
Non-childbearing potential is a female who is (defined as postmenopausal for at least 1
year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy]) or subjects and their partner practicing 1 of the following medically
acceptable methods of birth control:
- Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal
contraceptives for a minimum of 1 full Cycle (based on the subject's usual menstrual
Cycle period) before trial drug administration.
- Total abstinence from sexual intercourse since the last menses before trial drug
administration.
- Intrauterine device.
- Double barrier method (condoms, sponge, or diaphragm with spermicidal jellies or
cream.
o Male subjects must agree to use adequate birth control from the signature of the
informed consent form up until 30 days after the end of the Treatment Period.
- Subjects with neuropathic pain attributed to platinum and/or taxane chemotherapy for a
minimum of 3 months duration from screening.
- Subjects with cancer who have completed a chemotherapy regimen that included taxanes
or platinums (or in combination) and have no clinical evidence of actively progressive
disease. Subjects must have undergone at least a 90-Day washout period between the
last dose of cytotoxic chemotherapy/radiotherapy agent and randomization. Concurrent
hormonal therapy is permitted.
- Subjects with a score of 4 or higher out of 10 on the Diagnosing Neuropathic Pain-DN4
Questionnaire (Appendix F) at Screening.
- Subjects must have at least 10 non-missing scores in the 14 Days prior to
randomization during their Baseline Period.
- Subjects with moderate to severe neuropathic pain that has been stable for 14 Days.
Stable pain will be confirmed using an 11-point (0-10) NPRS. To establish moderate or
severe stable pain, the average daily pain scores during the 14-Day Baseline Period
must be ≥4 with fluctuation in the daily pain score of ≤2 points in increase or
decrease. Subjects with an average pain score >9 at Baseline will be excluded.
- Subjects with an Eastern Cooperative Oncology Group Performance Status score of 0 or 1
(Oken et al, 1982).
- Subjects who are able to communicate well with the trial staff and to comply with the
trial requirements (restrictions, appointments, and examination schedule).
- Subjects who are able to complete the trial-related questionnaires independently in
either English or in the local language.
- Subjects who sign an informed consent document (prior to the performance of any trial
related procedures).
Exclusion Criteria:
- History of peripheral neuropathy attributed to any cause other than platinum or taxane
chemotherapy (e.g., radiotherapy, vinca alkaloids, diabetes, alcohol, toxin,
hereditary, human immunodeficiency virus, or severe malnutrition).
- Subjects who have received TTX at any time prior to enrolment.
- Subjects receiving agents known to cause peripheral neuropathy within 90 Days of
randomization.
- Current use of any other therapy (including alternative nonmedical therapy) for the
treatment of neuropathic pain within 60 Days of randomization unless the dose is
stable for the 60 Days immediately prior to randomization. Subjects who fail this
criterion can be rescreened after 60 Days of stability.
- Subjects who used opioids within 14 Days of randomization or plan on using opioids
during the study period.
- Subjects who require rescue medication for breakthrough pain with medication other
than acetaminophen or Ibuprofen. Before and after randomization, acetaminophen will be
allowed at doses up to 650 mg of acetaminophen 4 times a Day <3 times a week or
Ibuprofen will be allowed at doses up to 400 mg 3 times a Day <3 times a week.
- Any concomitant medication that prolongs the QT or QRS interval unless on a stable
dose for 60 Days prior to randomization.
- Subjects with known impaired renal function or have screening GFR < 50 mL/min/1.73 m2
(using MDRD formula).
- Subjects who have not recovered from all toxicities related to chemotherapy to < grade
1 or mild AE's with the exception of CINP.
- Subjects who have inadequate organ function tests including: Hgb < 10 g/dl; ANC <
1500/µL; Plt. count < 100,000/µL; liver function (ALT and/or AST) more than 2 times
the upper limit of normal.
- Subjects with urinary retention.
- Subjects with documented bone metastases at the time of trial entry.
- Subjects with predicted life expectancy of <8 months.
- Subjects scheduled for chemotherapy or radiotherapy between Screening and the End of
Trial visit (Week 13).
- Current use of lidocaine (including Lidoderm) and other types of sodium channel
antiarrhythmic drugs within 30 Days of randomization.
- Subjects who have been injected with Botulinum toxin (e.g., Botox®) in the 3 months
prior to randomization, or who plan to receive a Botulinum toxin injection during the
study period.
- Subjects who require regular antiemetic medication.
- Current use of tricyclic antidepressant medication, anticonvulsants, or monoamine
oxidase inhibitors. Stable use of those medications for at least 2 months is
permissible if the subject has qualifying pain and plans to remain on a stable dose
throughout the trial.
- Subjects will be excluded if they have a current diagnosis of Major Depressive
Disorder.
- Subjects with current uncontrolled asthma, carbon dioxide retention, or oxygen
saturation <92% on room air, or require oxygen therapy at any concentration.
- Subjects with second- or third-degree heart block or prolonged QTc interval (corrected
for rate) on screening electrocardiogram (ECG) (i.e., confirmed >450 msec for men and
>470 msec for women on repeated occasion) or any other active cardiac arrhythmia or
abnormality that might constitute a clinical risk (i.e., LBBB, pacemaker).
- Subjects with motor impairment / neuromuscular abnormalities of the neck or throat,
including clinically significant neuromuscular abnormalities affecting the vocal cords
or breathing apparatus (excluding the tongue).
- Use of an investigational agent within 30 Days prior to Screening or scheduled to
receive an investigational drug other than TTX during the course of the trial.
- History of alcoholism, including binge drinking considered excessive in the opinion of
an investigator, within 12 months, or routine use of ethanol averaging > 3 units of
alcohol per Day.
- Significant history of drug dependency in the opinion of the investigator, including
prescription drug abuse or positive urine drug screening.
- Women who are pregnant or breast feeding.
- Any other condition that in the opinion of the investigators is likely to interfere
with treatment, impede data collection, or that poses a risk to the subject.