Diabetic Neuropathic Pain Relief, 6 Weeks Dosage Sublingual Water-soluble CBD/PEA

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether the DIA/NPR-6 is a better pain reliever in patients with diabetic neuropathic pain of the feet compared to placebo.

Detailed Description
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Subjects will be enrolled in the study for a maximum of 63 days, including an optional 14-day screening period, 42 days of active product administration, and followed by post-treatment blood work, EKG, and questionnaires within 24-hours following study treatment completion and a psychiatric and primary health care provider evaluation within 1 week of trial completion. The primary objective of this study is: To evaluate the impact of PGP-010-50-1 on subject's painful diabetic neuropathic pain (pDNP), anxiety, and sleep quality compared to a placebo control. To evaluate the impact of PGP-010-50-1 on the subject's impression of their response to the treatment compared to a placebo control. The secondary objectives of this study are: To evaluate the safety of PGP-010-50-1 for the treatment of painful diabetic peripheral neuropathy (DPN) of the feet compared to a placebo control To evaluate PGP-010-50-1 on liver function. To evaluate PGP-010-50-1 on Hbg A1C

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial Using Cannabidiol and Palmitoylethanolamide for the Treatment of Painful Diabetic Peripheral Neuropathy of the Feet

Conditions
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Diabetic Peripheral Neuropathic Pain

Intervention / Treatment
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* Drug: CBD/PEA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 21 years of age. Subject is or under the age of 65 years of age. Subject has a primary health care provider and gives permission for PG Pharma to contact the primary health care provider. Subject has a diagnosis of diabetic neuropathic pain of the feet . Subject has a mean pain scale score of ≥ 4 and ≤ 8 recorded localized to the foot in the 7 days prior to randomization. If female, the subject is postmenopausal (> 1 year), surgically sterile (> 3 months), had a hysterectomy, or is currently using 2 effective forms of birth control. Subject has not taken marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD for at least 14 days prior to this study, and agrees to not take marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD while participating in this study. Subject is willing to provide his/her written informed consent to participate in the study as stated in the informed consent document. Subject has a smart phone, knows how to use it, and is willing to use it for accessing and interacting with an electronic diary to enter trial information for the duration of the study - 57 days. (up to 14-day screening period and 42 days active dosing and 1 day post dosing. Exclusion Criteria: Subject is pregnant or lactating. Subject is unwilling to utilize two forms of birth control with partner. Male subject is unwilling to agree to not donate sperm from the time of dosing until 90 days after dosing of study drug. Subject has an allergy to cannabis, the Cannabaceae plant family (e.g., hemp, hops), palmitoylethanolamide, or terpenes. Subject has a known allergy to active or inert ingredients of the investigational product. Subject is taking a concomitant medication or treatment that would complicate use or interpretation of the study drug's effects (examples include: Cannabis or any cannabinoid products; Any drug or herbal product that influences the endocannabinoid system (ECS)). However, subjects are allowed to continue gabapentin and pregabalin medications, if the subject still meets the pain scale inclusion criteria, evidencing lack of effectiveness of their concomitant pain medication. Subjects on SNRIs or SSRIs. Subject is taking marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD for at least 14 days prior to this study, and does not promise that they will not take marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD while participating in this study; Subject has shortness of breath. Subject has uncontrolled asthma. Subject has a fever and/or productive cough. Subject has unstable angina, uncontrolled hypertension. Subject currently or has a history of congestive heart failure. Subject meets any DSM-V criteria for current, major psychiatric illness, including but not limited to: bipolar disorder, major depressive disorder, psychosis, or substance abuse disorder. Subject has a personal or family history of schizophrenia. Subject has a personal history or currently has suicidal ideation or attempted suicide. Subject has a major neurological disorder, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain injury/head injury, and seizures. Subject has a history of multiple sclerosis. Subject is currently taking any form of opioids. Subject has a history of substance or alcohol abuse. Subject has clinically significant illness, including cardiovascular disorders. Subject has any condition in which the investigator believes will confound the data of the study or could put the subject at risk of harm. Subject does not have access to a smart phone or does not know how to use a smart phone application. Subject is not within 30 miles of a Quest Diagnostics laboratory. The skin under the tongue or anywhere in the oral cavity is not intact. Subject has abnormal liver function test results. Subject has a history of abnormal liver dysfunction or liver pathology.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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
Interventional Model Description: There are 2 groups in this trial: interventional group (active drug) and control group (placebo).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD/PEA<br>Subject will receive a 42-day supply of 10/50 mg CBD/PEA sublingual tablets to be taken 3 times a day for 42 days. | Drug: CBD/PEA<br>* A water-soluble sublingual tablet containing 10/50 mg of CBD/PEA.<br>* Other names: PGP-DPN-10/50;|
| Placebo Comparator: Placebo Control<br>A placebo sublingual tablet to be taken three times a day for 42 days. | Drug: Placebo<br>* An inactive compound.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain as assessed by Numerical Pain Rating Scale (NPRS) | To evaluate the impact of DIA/NPR-6 on the subject's neuropathic pain as assessed by utilizing a Numeric Pain Rating Scale (NPRS). NPRS is from 0-10, where higher scores indicate worse pain, and lower scores indicate less pain reported by the subject. | Six Weeks | 
| Pain as measured by the Brief Pain Inventory (BPI) | To evaluate the impact of DIA/NPR-6 on the subject's neuropathic pain as assessed by utilizing a Brief Pain Inventory (BPI) where patients will answer 15 questions regarding their pain. | Six Weeks | 
| Anxiety as measured by the Self-Rating Anxiety Scale (SAS) | To evaluate the impact of DIA/NPR-6 on the subject's anxiety as assessed by the Self-Rating Anxiety Scale (SAS). Subjects will complete SAS prior to first dose and during post-treatment. | Six Weeks | 
| Sleep as measured by the Pittsburg Sleep Quality Index (PSQI) | To evaluate the impact of DIA/NPR-6 on the subject's sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI). Subjects will be evaluated pre- and post-treatment. The PSQI produces a global score and 6 subscales, Subjective Sleep Quality, Sleep Latency, Sleep Duration, Habitual Sleep Efficiency, Sleep Disturbances, Use of Sleeping Medications, and Daytime Dysfunction. | Six Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-related adverse events as assessed by CTCAE v4.0 | To evaluate the safety of DIA/NPR-6 for the treatment of painful DPN of the feet compared to a placebo control assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. | Six Weeks | 
| Subject's Response to Treatment as assessed by Patient's Global Impression of Change (PGIC) | To evaluate the impact of DIA/NPR-6 on the subject's impression of their response to the treatment compared to a placebo control as assessed by Patient's Global Impression of Change (PGIC). Subjects indicate their overall impression of their response to treatment on 0-10 scale, where a higher number represents the subject feeling worse than before the intervention, and a lower number represents the subject feeling better than before the intervention. | Six Weeks |