A Prospective Clinical Trial to Evaluate the Efficacy and Safety of Neurotropic B-Vitamins in Clinically Diagnosed Peripheral Sensory Polyneuropathy of Different Etiologies.

Study Overview
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Brief Summary
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This study is designed to investigate the efficacy of the Test Product in subjects with clinically diagnosed peripheral sensory polyneuropathy of different etiologies compared to placebo.

Detailed Description
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This prospective, multi-center, randomized, double-blind, placebo-controlled, parallel-group Phase III clinical study is designed to investigate the efficacy and safety of the Test product versus placebo in male and non-pregnant female subjects with clinically diagnosed peripheral sensory polyneuropathy of different etiologies aged 18 to 70 years. The study will be conducted in 17 sites in Mexico. 318 patients with clinically diagnosed symptoms of peripheral sensory polyneuropathy of different etiologies who fulfill the inclusion and exclusion criteria will be enrolled and randomized in a 1:1 ratio to receive either oral vitamin B combination daily or matching placebo for 120 days. The primary and secondary outcome measures will be evaluated at each post-Screening visit. Exploratory outcomes, and safety/tolerability/treatment satisfaction assessments will be evaluated as per schedule of activities. Approvals were obtained from Local Ethics Committees and from Mexican Regulatory Authority (COFEPRIS).

Official Title
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A Prospective, Multicenter, Randomized, Double Blind, Placebo-controlled Parallel Group Clinical Trial to Evaluate the Efficacy and Safety of the Product Vitamins B1 (100mg), B6 (100 mg), Plus B12 (5 mg) in Tablets in Subjects With Clinically Diagnosed PerIpheral Sensory polyNeuropathy of Different etiologieS (PINS Study)

Conditions
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Peripheral Sensory Neuropathy of Different Etiologies

Intervention / Treatment
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* Drug: Vitamin B combination tablet
* Drug: Placebo Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand the purpose and risks of the study Considered reliable and capable of adhering to protocol, visit schedule, and medication administration instructions Demonstrates that participant can successfully complete the study eDiary using electronic device Male or female, 18 to 70 years of age (inclusive) Subjects with symptoms of peripheral sensory polyneuropathy (measured with MNSI scale) NTSS-6 total score at Screening and Baseline: no severe symptoms Duration of peripheral sensory polyneuropathy symptoms ≥6 months Blood pressure ≤140/90 mmHg at Screening or taking a stable dose of antihypertensive medication Diabetes: diagnosed T1DM or T2DM ≥ 1 year prior Screening, HbA1c <9% at Screening, no severe hyper-/hypoglycemia/ketoacidosis Stable on allowed concomitant medication Contraception for women of childbearing potential and men with potentially fertile female partner Exclusion Criteria: Subjects with genetic, autoimmune, inflammatory and chemotherapy-induced peripheral neuropathy (PN), compressive mononeuropathy of lower extremity Subacute onset of peripheral sensory polyneuropathy No increase in PN symptoms for 1 y or longer Pain in the rest of the body higher than pain in the lower limbs from peripheral sensory polyneuropathy Fails to successfully submit eDiary data Known hypersensitivity to vitamins B1, B6, or B12 Taken vitamin supplement containing vitamins B1, B6, B12, E, D higher than RDA Taken alpha lipoic acid Taken any cytostatic drug Taken anti-epileptics, opioids or other drugs for neuropathic pain management. Use of cannabis/cannabidiol Taken topical medication that alters sensation of assessment Subjects with any active systemic infection or disease that requires antibiotics, antifungals, antiviral agents BMI ≥35 kg/m2 Pregnancy, subjects planning to become pregnant, or breastfeeding subjects

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin B combination tablet (B1, B6, B12)<br> | Drug: Vitamin B combination tablet<br>* Once daily, with some liquid with or after a meal<br>|
| Placebo Comparator: Placebo tablet<br> | Drug: Placebo Tablet<br>* Once daily, with some liquid with or after a meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathy Total Symptom Score-6 (NTSS-6) | The NTSS-6 scale is a validated neuropathy symptoms scale which evaluates the frequency and intensity of 6 neuropathy sensory symptoms in feet and legs such as numbness, prickling sensation, burning/aching/lancinating pain and allodynia. | 120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Questionnaire | The Quality of Life Questionnaire is a reliable, and valid measure of physical and mental health. | 120 days | 
| modified Toronto Clinical Neuropathy Score (mTCNS) sensory test subscores | The mTCNS is a reliable clinical score with high validity for tracking mild to moderate distal symmetric polyneuropathy (DSP) and is sensitive to early DSP changes. | 120 days | 
| B vitamins blood levels | Assess the effect of the Test Product on concentrations of vitamins B1, B6, and B12 | 120 days | 
| Safety Data | Safety of Vitamin B combination tablet in patients with peripheral sensory polyneuropathy in the feet comparing the incidence of adverse and serious adverse events, and the incidence of clinically significant laboratory values to Placebo Incidence of adverse events (AEs) and serious adverse events (SAEs) Incidence of clinically significant laboratory values | 120 days |