search
Back to results

A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain

Primary Purpose

Chemotherapy-induced Neuropathic Pain, Chemotherapy-induced Peripheral Neuropathy

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tetrodotoxin
Placebo
Sponsored by
Wex Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chemotherapy-induced Neuropathic Pain focused on measuring CINP, Neuropathy

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Providence Medical FoundationRecruiting
  • MEDSOL Clinical Research CenterRecruiting
  • SUNY Upstate Medical UniversityRecruiting
  • Neurotherapy MontrealRecruiting
  • Raven Bailey

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Tetrodotoxin for injection

Placebo

Arm Description

30 µg, 1 ml SC injection in the thigh or abdomen, twice daily for 4 Days

1.0 mL of placebo, SC injection in the thigh or abdomen, twice daily for 4 Days

Outcomes

Primary Outcome Measures

NPRS Pain reduction - at week 4
The Change from Baseline (average of Days -14 to -1) at Week 4 in average weekly NPRS scores in subjects treated with TTX compared to Placebo

Secondary Outcome Measures

NPRS Pain reduction - at week 8
The Change from Baseline (average of Days -14 to -1) at Week 8 in average weekly NPRS scores in subjects treated with TTX compared to Placebo
NPRS Pain reduction - at week 12
The Change from Baseline (average of Days -14 to -1) at Week 12 in average weekly NPRS scores in subjects treated with TTX compared to Placebo

Full Information

First Posted
April 25, 2022
Last Updated
August 21, 2023
Sponsor
Wex Pharmaceuticals Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT05359133
Brief Title
A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain
Official Title
A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 19, 2022 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wex Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Neuropathic Pain, Chemotherapy-induced Peripheral Neuropathy
Keywords
CINP, Neuropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
222 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tetrodotoxin for injection
Arm Type
Active Comparator
Arm Description
30 µg, 1 ml SC injection in the thigh or abdomen, twice daily for 4 Days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
1.0 mL of placebo, SC injection in the thigh or abdomen, twice daily for 4 Days
Intervention Type
Drug
Intervention Name(s)
Tetrodotoxin
Other Intervention Name(s)
Halneuron
Intervention Description
TTX for Injection, 30 µg/mL, is a sterile, nonpyrogenic, white, lyophilized powder provided in a 5 mL glass single-use vial with a rubber stopper and aluminum overseal. Upon reconstitution of the lyophilized product with 1.1 mL of sterile water for injection, each vial delivers 1 mL of fluid containing 30 µg of TTX with a pH of 4.0 to 5.5
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sterile 0.9% sodium chloride injection
Intervention Description
Placebo for injection is a sterile 0.9% sodium chloride injection or normal saline for injection. To ensure blinding, subjects receiving placebo will receive the same volume (1.0 mL) for injection to match the volume used for the cohorts assigned to receive active trial drug. Route and frequency: 1.0 mL of placebo, SC injection in the thigh or abdomen, twice daily for 4 Days in each treatment Cycle.
Primary Outcome Measure Information:
Title
NPRS Pain reduction - at week 4
Description
The Change from Baseline (average of Days -14 to -1) at Week 4 in average weekly NPRS scores in subjects treated with TTX compared to Placebo
Time Frame
At week 4
Secondary Outcome Measure Information:
Title
NPRS Pain reduction - at week 8
Description
The Change from Baseline (average of Days -14 to -1) at Week 8 in average weekly NPRS scores in subjects treated with TTX compared to Placebo
Time Frame
At week 8
Title
NPRS Pain reduction - at week 12
Description
The Change from Baseline (average of Days -14 to -1) at Week 12 in average weekly NPRS scores in subjects treated with TTX compared to Placebo
Time Frame
At week 12
Other Pre-specified Outcome Measures:
Title
AUC up to week 12
Description
AUC calculated on the Change from Baseline through Week 12 in weekly average NPRS scores.
Time Frame
baseline to week 12
Title
NPRS Pain reduction - weekly
Description
Change from Baseline to each study week through Week 12 in Average Weekly NPRS scores
Time Frame
baseline to week 12
Title
NPRS Pain reduction - weekly
Description
Percent Change from Baseline to each study week through Week 12 in Average Weekly NPRS scores
Time Frame
baseline to week 12
Title
Subjects with at least 30% reduction in pain
Description
Proportion of responders at Week 12, defined as subjects showing a 30% or greater reduction from overall Baseline (Week -1 & week -2) to Week 12 in weekly average NPRS score.
Time Frame
baseline to week 12 (assessed weekly)
Title
Subjects with at least 50% reduction in pain
Description
Proportion of responders at Week 12, defined as subjects showing a 30% or greater reduction from overall Baseline (Week -1 & week -2) to Week 12 in weekly average NPRS score.
Time Frame
baseline to week 12 (assessed weekly)
Title
Time to response
Description
Time to first response defined as (30%/50%) reduction from overall Baseline in weekly average NPRS score
Time Frame
Day 1 to week 12
Title
Duration of response
Description
Duration of response defined as time from initial (30%/50%) reduction from overall baseline in weekly average NPRS score to first loss of response.
Time Frame
Day 1 to week 12
Title
BPI change
Description
Change from Baseline to each study visit through Week 12 in quality of life and pain intensity measures using the Brief Pain Inventory (BPI).
Time Frame
Baseline to Week 12
Title
NPSI change
Description
Change from Baseline to each study visit through Week 12 in neuropathic pain symptoms using the Neuropathic Pain Symptoms Inventory (NPSI)
Time Frame
Baseline to Week 12
Title
POMS change
Description
Change from Baseline to each study visit through Week 12 in Profile of Mood States (POMS2) total mood disturbance, and each of the 6 specific subscales.
Time Frame
Baseline to Week 12
Title
Percent of subjects taking Rescue Medication
Description
Percentage of subjects taking allowed and prohibited rescue medication at each week, including Week 12.
Time Frame
Baseline to Week 12
Title
Average rescue medication consumed
Description
Average per-subject consumption of allowed and prohibited rescue medication at each week, including Week 12
Time Frame
Baseline to Week 12
Title
Patient global impression of change questionnaire
Description
Subjects' Global Impression of Change responses at each visit through the End-of-Trial visit.
Time Frame
at week 12
Title
Proportion of responders (30%/50%)
Description
Proportion of responders (30%/50%) at each study week through Week 12
Time Frame
weekly until week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mehran Kavoosi
Phone
6046767900
Email
mehrank@wexpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter Korz
Organizational Affiliation
COO
Official's Role
Study Director
Facility Information:
Facility Name
Providence Medical Foundation
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tracy Foster
Phone
707-521-3836
Email
tracy.foster@stjoe.org
Phone
(707) 521-3830
First Name & Middle Initial & Last Name & Degree
Ian Anderson, M.D.
Facility Name
MEDSOL Clinical Research Center
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Vasconcelos
Phone
941-623-9744
Email
mvasconcelos@medsolcrc.com
First Name & Middle Initial & Last Name & Degree
George Li, M.D.
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Clark
Phone
315-464-8276
Email
clarksar@upstate.edu
First Name & Middle Initial & Last Name & Degree
Mary Cunningham, M.D.
Facility Name
Neurotherapy Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3P 3E5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Soufiane Boucetta, Ph.D.
Phone
(514) 481-7867
Ext
110
Email
sboucetta@neuromtl.com
Phone
(514) 233-9693
First Name & Middle Initial & Last Name & Degree
Gilbert Blaise, M.D.
Facility Name
Raven Bailey
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raven Bailey
Email
RABailey@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Salahadin Abdi, M.D.

12. IPD Sharing Statement

Learn more about this trial

A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain

We'll reach out to this number within 24 hrs