A Phase 2a Study to Assess Safety & Pharmacokinetics of Sustained Release Sodium Nitrite in Patients With Diabetic Pain

A Randomized, Double-blinded, Phase 2a Study to Assess the Safety and Pharmacokinetics of a Sustained Release Formulation of Sodium Nitrite (TV1001sr) in Patients With Diabetic Neuropathic Pain (DNP)

In this study, subjects with diabetic neuropathic pain (DNP) will be treated for 12 weeks with either placebo, 40 or 80 mg sustained release sodium nitrite (TV1001sr) twice daily. Primary endpoints will be safety and pharmacokinetics. Assessment of the study medications affects on pain following treatment will also be recorded.

This is a dose-ranging study to evaluate the safety, pharmacokinetics, and tolerability of multiple doses of an oral, sustained release formulation of sodium nitrite (TV1001sr) in subjects with DNP. The primary objective is to assess the safety and tolerability of multiple doses of twice daily 40 mg and 80 mg TV1001sr compared with placebo over a 12 week treatment period and the pharmacokinetics of the sustained release formulation of sodium nitrite. Secondary objectives are to evaluate the pharmacokinetics and markers of functional improvement including pain questionnaires, quantitative sensory testing and changes in markers of diabetes.

Inclusion Criteria:

• Female subjects must be post-menopausal, sterilized or using suitable birth control
• Diagnosis of diabetes (HbA1c > 6.0)
• Diagnosis of diabetic peripheral neuropathy pain in feet
• Presence of ongoing diabetic neuropathic for at least 3 months
• A pain score of greater than or equal to 4 on the Numerical Pain Rating Scale at screening
• Ability to provide written informed consent

Exclusion Criteria:

• Patients with fibromyalgia or regional pain caused by lumbar or cervical compression
• History or diagnosis of significant neurological disease
• History and diagnosis of clinically significant psychiatric diseases
• Serious liver disease
• Poorly controlled diabetes
• Hypersensitivity to sodium nitrite or related compounds
• Life expectancy < 6 months
• A chronic illness that may increase the risks associated with this study
• Active malignancy requiring active anti-neoplastic therapy that will, in the opinion of the investigator, interfere with study treatment or participation
• Pregnant or nursing women
• Current diagnosis of alcohol or other substance abuse
• Current use of sildenafil or other phosphodiesterase Type 5 Inhibitors
• History of methemoglobinemia, (met-Hb ≥ 15%)
• Subject is involved in litigation or receives worker's compensation
• Inability to speak English