TTX-CINP-201: The Purpose of This Study is to Determine if Tetrodotoxin (TTX) is Effective in the Treatment of Pain Resulting From Chemotherapy Treatment

• Sponsor: Wex Pharmaceuticals Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01655823
• Collaborator: Premier Research Group plc (Industry)
• Enrollment: 125
• Locations: 23
• Arms: 5
• Duration (Months): 31.4
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pain; Peripheral Neuropathy; Neuropathic Pain	Drug: Placebo; Drug: Tetrodotoxin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Dose-Finding, Placebo Controlled, Phase II Multicenter Study of Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Feb 11, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo (twice daily) Placebo for injection (1 ml volume), twice a day for four consecutive days.	Drug: Placebo; Sham treatment acting as control arm; Other Names: placebo for injection
Experimental: Low dose Tetrodotoxin (twice daily) Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.	Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection
Experimental: Mid-range dose of Tetrodotoxin (twice daily) Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.	Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection
Experimental: 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.	Drug: Placebo; Sham treatment acting as control arm; Other Names: placebo for injection ; Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection
Experimental: Max dose Tetrodotoxin (twice daily) Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.	Drug: Tetrodotoxin; Comparison of different dosages of Tetrodotoxin; Other Names: TTX for injection

Outcome Measures

Primary Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lalita Pandit	Fountain Valley	California	United States	92708
2	Robert Moss	Fountain Valley	California	United States	92708
3	Alliance Research Centers	Laguna Hills	California	United States	92653
4	Global Research Management	Los Angeles	California	United States	90027
5	Innovative Clinical Research	Los Angeles	California	United States	90603
6	El Camino Cancer Center	Mountain View	California	United States	94040
7	Pacific Cancer Care	Salinas	California	United States	93901
8	Redwood Regional Medical Group	Santa Rosa	California	United States	95403
9	St. Vincent's Medical Center	Bridgeport	Connecticut	United States	06606
10	Medsol Clinical Research Center	Port Charlotte	Florida	United States	33952
11	Axcess Medical Research	Wellington	Florida	United States	33414
12	Cancer Center of Middle Georgia	Dublin	Georgia	United States	31021
13	Cancer Center of Kansas	Wichita	Kansas	United States	67214
14	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
15	St. Louis Cancer Care	Bridgeton	Missouri	United States	63044
16	Mercy Medical Research Institute	Springfield	Missouri	United States	65807
17	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
18	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico	United States	87103
19	Signal Point Clinical Research Center	Middletown	Ohio	United States	45042
20	Institute of Pain Research	Oklahoma City	Oklahoma	United States	73104
21	Gettysburg Cancer Center	Gettysburg	Pennsylvania	United States	17325
22	University of Texas Southwestern	Dallas	Texas	United States	75390-9179
23	Jean Brown Research	Salt Lake City	Utah	United States	84124

Sponsors and Collaborators

• Wex Pharmaceuticals Inc.
• Premier Research Group plc

Investigators

• Principal Investigator: Samuel Goldlust, MD, Hackensack University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wex Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT01655823
• Other Study ID Numbers: TTX-CINP-201
• First Posted: Aug 2, 2012
• Last Update Posted: Oct 30, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Wex Pharmaceuticals Inc.: Pain; Puffer fish; Tetrodotoxin; TTX; Neuropathy; Chemotherapy; WEX Pharmaceuticals
• Additional relevant MeSH terms: Neuralgia; Peripheral Nervous System Diseases; Tetrodotoxin

Study Results

Participant Flow

Arm/Group Title	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)
Arm/Group Description	Placebo for injection (1 ml volume), twice a day for four consecutive days. Placebo: Sham treatment acting as control arm	Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin	Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin	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	Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin
Period Title: Overall Study
STARTED	25	25	24	25	26
COMPLETED	25	23	24	24	25
NOT COMPLETED	0	2	0	1	1

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	Placebo for injection (1 ml volume), twice a day for four consecutive days. Placebo: Sham treatment acting as control arm	Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin	Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin	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	Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin	Total of all reporting groups
Overall Participants	25	25	24	25	26	125
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.0 (10.3)	59.1 (10.29)	61.4 (10.01)	60.4 (10.28)	60.6 (11.05)	60.1 (10.28)
Sex: Female, Male (Count of Participants)
Female	15 60%	16 64%	15 62.5%	15 60%	16 61.5%	77 61.6%
Male	10 40%	9 36%	9 37.5%	10 40%	10 38.5%	48 38.4%
Region of Enrollment (participants) [Number]
United States	25 100%	25 100%	24 100%	25 100%	26 100%	125 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28.
Description	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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	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)
Arm/Group Description	Placebo for injection (1 ml volume), twice a day for four consecutive days. Placebo: Sham treatment acting as control arm	Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin	Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin	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	Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin
Measure Participants	25	25	24	25	26
Baseline	6.662 (1.4832)	6.285 (1.3312)	7.012 (1.3706)	6.240 (1.1743)	6.255 (1.3561)
Mean Scores for Days 22-28	5.323 (2.2765)	5.005 (2.0451)	5.987 (2.2531)	4.566 (2.4931)	4.749 (1.7701)
Change from Baseline in Mean Scores for Days 22-28	-1.339 (2.0681)	-1.269 (1.3959)	-1.052 (1.5742)	-1.682 (2.3231)	-1.529 (1.8203)

Adverse Events

Arm/Group Title	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)
Arm/Group Description	Placebo for injection (1 ml volume), twice a day for four consecutive days. Placebo: Sham treatment acting as control arm		Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin		Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin		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		Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days. Tetrodotoxin: Comparison of different dosages of Tetrodotoxin
All Cause Mortality
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/25 (4%)		0/25 (0%)		1/24 (4.2%)		0/25 (0%)		1/26 (3.8%)
Infections and infestations
Viral upper respiratory tract infection	0/25 (0%)		0/25 (0%)		0/24 (0%)		0/25 (0%)		1/26 (3.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic carcinoma of bladder and Prostate cancer	0/25 (0%)		0/25 (0%)		1/24 (4.2%)		0/25 (0%)		0/26 (0%)
Colon cancer metastatic	1/25 (4%)		0/25 (0%)		0/24 (0%)		0/25 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/25 (72%)		21/25 (84%)		22/24 (91.7%)		20/25 (80%)		24/26 (92.3%)
Nervous system disorders
Paraesthesia	6/25 (24%)		5/25 (20%)		7/24 (29.2%)		5/25 (20%)		10/26 (38.5%)
Hypoaesthesia	2/25 (8%)		2/25 (8%)		1/24 (4.2%)		2/25 (8%)		1/26 (3.8%)
headache	5/25 (20%)		6/25 (24%)		3/24 (12.5%)		1/25 (4%)		9/26 (34.6%)
dizziness	5/25 (20%)		3/25 (12%)		4/24 (16.7%)		3/25 (12%)		8/26 (30.8%)
Paraesthesia Oral	3/25 (12%)		4/25 (16%)		9/24 (37.5%)		10/25 (40%)		11/26 (42.3%)
Hypoaesthesia Oral	3/25 (12%)		5/25 (20%)		7/24 (29.2%)		6/25 (24%)		10/26 (38.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.