Neuropathic Pain, Pain, Peripheral Neuropathy
Conditions
Keywords
Pain, Puffer fish, Tetrodotoxin, TTX, Neuropathy, Chemotherapy, WEX Pharmaceuticals
Brief summary
Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of many chemotherapeutic agents including vincristine, paclitaxel, cisplatin, oxaliplatin, bortezomib and ixabepilone. Chemotherapy-induced peripheral neuropathy commonly occurs in greater than 40% of patients. To improve the peripheral neuropathy, the chemotherapy dosing is often either decreased or discontinued potentially affecting tumor responsiveness, prognosis, and survival. There is an unmet medical need for treatment of cancer patients with chemotherapy induced neuropathic pain (CINP) and the proposed study will investigate the efficacy and safety of multiple dose levels of tetrodotoxin (TTX) versus placebo in moderate to severe neuropathic pain caused by chemotherapy.
Interventions
DRUGPlacebo
Sham treatment acting as control arm
DRUGTetrodotoxin
Comparison of different dosages of Tetrodotoxin
Sponsors
Premier Research
Wex Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* If female, not of childbearing potential. * Patients with documented neuropathic pain * Cancer Patients who have completed a chemotherapy regimen which included taxanes or platinums (or both) and have no evidence actively progressive disease. Concurrent hormonal therapies are allowed * Patients with stable moderate to severe neuropathic pain * Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. * Patients who are able to complete the study-related questionnaires independently in either English or Spanish.
Exclusion criteria
* History of peripheral neuropathy attributed to any cause other than chemotherapy. * Patients receiving any concurrent agents known to cause peripheral neuropathy within 30 days of Randomization. * Current use of other therapy (ies), including alternative therapies, for treatment of peripheral neuropathy within 30 days of Randomization (with the exception of protocol allowed concurrent medications). * Patients who used controlled release opioids within seven days of baseline period or who expect to use controlled release opioids at any time from baseline to end of study. * Patients with abnormal kidney function. * Patients with bone metastases. * Patients scheduled for treatment for their cancer with chemotherapy or radiotherapy between screening and the end of study visit. * Current use of lidocaine and other types of antiarrhythmic drugs within 30 days of Randomization. * Current use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine within 30 days of Randomization. * Current cause of Chemotherapy Induced Neuropathic Pain attributed to Velcade (Bortezomib) or vinca alkaloids or analogues such as vincristine, vinblasine, vinorelbine and vindesine. * Current use of tricyclic antidepressant medication, anticonvulsants and monoamine oxidase inhibitors. * Patients with current uncontrolled asthma or lung disease. * Patients with significant heart disease. * Use of an investigational agent within 30 days prior to screening or is scheduled to receive an investigational drug other than TTX during the course of the study. * Females who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Day 22 to Day 28 | The primary efficacy endpoint for Part I was the change from baseline in weekly average NPRS scores at 22 to 28 days after treatment. Baseline was defined as the average of NPRS scores for the last 7 days prior to dosing. Pain was assessed using a Numerical Pain Rating Scale (NPRS) with a range of 0 (no pain) to 10 (extreme pain). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Twice Daily) Placebo for injection (1 ml volume), twice a day for four consecutive days.
Placebo: Sham treatment acting as control arm | 25 |
| Low Dose Tetrodotoxin (Twice Daily) Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.
Tetrodotoxin: Comparison of different dosages of Tetrodotoxin | 25 |
| Mid-range Dose of Tetrodotoxin (Twice Daily) Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.
Tetrodotoxin: Comparison of different dosages of Tetrodotoxin | 24 |
| Max Dose Tetrodotoxin (Once Daily) Max dose Tetrodotoxin injectable (1 ml volume), once a day in the morning for four consecutive days and Placebo for injection (1 ml volume), once a day in the afternoon for four consecutive days. Total of 4 treatment days.
Placebo: Sham treatment acting as control arm
Tetrodotoxin: Comparison of different dosages of Tetrodotoxin | 25 |
| Max Dose Tetrodotoxin (Twice Daily) Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.
Tetrodotoxin: Comparison of different dosages of Tetrodotoxin | 26 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo (Twice Daily) | Low Dose Tetrodotoxin (Twice Daily) | Mid-range Dose of Tetrodotoxin (Twice Daily) | Max Dose Tetrodotoxin (Once Daily) | Max Dose Tetrodotoxin (Twice Daily) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 10.3 | 59.1 years STANDARD_DEVIATION 10.29 | 61.4 years STANDARD_DEVIATION 10.01 | 60.4 years STANDARD_DEVIATION 10.28 | 60.6 years STANDARD_DEVIATION 11.05 | 60.1 years STANDARD_DEVIATION 10.28 |
| Region of Enrollment United States | 25 participants | 25 participants | 24 participants | 25 participants | 26 participants | 125 participants |
| Sex: Female, Male Female | 15 Participants | 16 Participants | 15 Participants | 15 Participants | 16 Participants | 77 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 9 Participants | 10 Participants | 10 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 25 | 21 / 25 | 22 / 24 | 20 / 25 | 24 / 26 |
| serious Total, serious adverse events | 1 / 25 | 0 / 25 | 1 / 24 | 0 / 25 | 1 / 26 |
Outcome results
Primary
Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28.
The primary efficacy endpoint for Part I was the change from baseline in weekly average NPRS scores at 22 to 28 days after treatment. Baseline was defined as the average of NPRS scores for the last 7 days prior to dosing. Pain was assessed using a Numerical Pain Rating Scale (NPRS) with a range of 0 (no pain) to 10 (extreme pain).
Time frame: Day 22 to Day 28
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Baseline | 6.662 11 point units on a scale | Standard Deviation 1.4832 |
| Placebo (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Change from Baseline in Mean Scores for Days 22-28 | -1.339 11 point units on a scale | Standard Deviation 2.0681 |
| Placebo (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Mean Scores for Days 22-28 | 5.323 11 point units on a scale | Standard Deviation 2.2765 |
| Low Dose Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Mean Scores for Days 22-28 | 5.005 11 point units on a scale | Standard Deviation 2.0451 |
| Low Dose Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Baseline | 6.285 11 point units on a scale | Standard Deviation 1.3312 |
| Low Dose Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Change from Baseline in Mean Scores for Days 22-28 | -1.269 11 point units on a scale | Standard Deviation 1.3959 |
| Mid-range Dose of Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Mean Scores for Days 22-28 | 5.987 11 point units on a scale | Standard Deviation 2.2531 |
| Mid-range Dose of Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Baseline | 7.012 11 point units on a scale | Standard Deviation 1.3706 |
| Mid-range Dose of Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Change from Baseline in Mean Scores for Days 22-28 | -1.052 11 point units on a scale | Standard Deviation 1.5742 |
| Max Dose Tetrodotoxin (Once Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Baseline | 6.240 11 point units on a scale | Standard Deviation 1.1743 |
| Max Dose Tetrodotoxin (Once Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Change from Baseline in Mean Scores for Days 22-28 | -1.682 11 point units on a scale | Standard Deviation 2.3231 |
| Max Dose Tetrodotoxin (Once Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Mean Scores for Days 22-28 | 4.566 11 point units on a scale | Standard Deviation 2.4931 |
| Max Dose Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Mean Scores for Days 22-28 | 4.749 11 point units on a scale | Standard Deviation 1.7701 |
| Max Dose Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Baseline | 6.255 11 point units on a scale | Standard Deviation 1.3561 |
| Max Dose Tetrodotoxin (Twice Daily) | Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28. | Change from Baseline in Mean Scores for Days 22-28 | -1.529 11 point units on a scale | Standard Deviation 1.8203 |