Safety & Efficacy Study of Subcutaneous Tetrodotoxin for Moderate to Severe Inadequately Controlled Cancer-related Pain

Inclusion criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

1. Male or female 18 years of age and over.
2. Inpatient or outpatient with a diagnosis of cancer.
3. Stable but inadequately controlled pain with current therapy for at least two weeks.
4. Experiencing somatic, visceral and/or neuropathic pain related to cancer.
5. 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.
6. Life expectancy of at least 3 months.
7. Ability to communicate well with the investigator and to comply with the requirements (restrictions, appointments, and examination schedule) of the entire study.
8. Signed informed consent document (prior to any study-related procedures being performed).

Exclusion criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

1. Planned initiation of chemotherapy, radiotherapy, or bisphosphonates within 30 days prior to randomization.
2. Use of anaesthetics.
3. Use of lidocaine and other types of antiarrhythmic drugs.
4. Use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine.
5. History of CO2 retention, or SaO2 \<80% either on room air or O2 of not greater than 2-4 L/min by nasal cannula.
6. 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.
7. 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.
8. Known hypersensitivity to puffer fish, tetrodotoxin and/or its derivatives.
9. 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.
10. 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).
11. Females with a positive serum pregnancy test at screening or positive urine pregnancy test on admission to study site.
12. 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.
13. 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