Cannabinoid Tablets for the Treatment of Pain From Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of PG-OA-10CN and PG-OA-5TH tablets as a better pain reliever in patients with moderate to severe chronic pain due to osteoarthritis of the knee than a placebo.

Detailed Description
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Subjects will be enrolled in the study for a maximum of 36 days, including a 7-day screening period, 28 days of active product administration, and followed by a post-treatment follow-up within 1 day. The primary objective of this study is: To evaluate the efficacy of PG-OA-10CN and PG-OA-5TH for the treatment of pain associated with osteoarthritis of the knee, compared to a placebo control. The secondary objectives of this study are: To evaluate differences of efficacy between PG-OA-10CN and PG-OA-5TH To evaluate the impact of PG-OA-10CN and PG-OA-5TH for stiffness, function in daily living, function in sport and recreation, and knee related quality of life as assessed by the KOOS. To evaluate the safety of PG-OA-10CN and PG-OA-5TH for the treatment of pain associated with osteoarthritis of the knee.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Three-Arm Trial Examining Sublingual Cannabinoid Tablets for the Treatment of Pain From Osteoarthritis of the Knee.

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: CBD/CBN
* Drug: CBD/THC
* 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 has a diagnosis of osteoarthritis of the knee as determined by the subject's primary care physician or related health care provider. Subject reports an average NPRS score of ≥ 5 in the 7 days prior to enrollment. 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. If subject is currently taking a prohibited medication, subject must be willing to and complete a washout of these medications during the screening period and prior to starting study treatment. Subject has not taken any NSAIDs and/or acetaminophen for at least 2 days prior to starting study treatment. Subject is willing to provide his/her written informed consent to participate in the study as stated in the informed consent document. Subject is willing to use an electronic diary to enter trial information for 29 days. Exclusion Criteria: Subject is pregnant or lactating; 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)); 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 is currently being treated with antibiotics for sinus, throat, or lung infections; Subject has shortness of breath associated with allergies; 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 has any other unstable medical condition; 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 taken pharmaceutical pain medicine, including OTC pain medicine of any kind, or has taken a NSAID and/or acetaminophen within 2 days of starting study treatment. Subject has taken a prohibited medication during the screening period and prior to starting study treatment or is unwilling to stop these medications. Subject has an allergy to, or has an intolerance to, NSAIDs or acetaminophen. Subject has taken any form of steroids, including a local steroid injection in the knee, within 1 month of starting study treatment. Subject has received any invasive interventions or surgery of the knee. 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.

Ages Eligible for Study
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Minimum Age: 21 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD/CBN<br>Participants will receive a 28-day supply of CBD/CBN sublingual tablets to be taken 3 times a day for 28 days. | Drug: CBD/CBN<br>* A water-soluble sublingual tablet containing 10 mg of CBD and 10 mg of CBN.<br>|
| Experimental: CBD/THC<br>Participants will receive a 28-day supply of CBD/THC sublingual tablets to be taken 3 times a day for 28 days. | Drug: CBD/THC<br>* A water-soluble sublingual tablet containing 10 mg of CBD and 5 mg of THC.<br>|
| Placebo Comparator: Placebo<br>A placebo sublingual tablet to be taken three times a day for 28 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 PG-OA-10CN and PG-OA-10TC on the subject's osteoarthritis of the knee 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. | 28 Days | 
| Pain as assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS) | To evaluate the impact of PG-OA-10CN and PG-OA-10TC on the subject's osteoarthritis of the knee pain as assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS is scored from 0-100, where 0 represents extreme problems and 100 represents no problems, as reported by the subject. | 28 Days | 

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 PG-OA-10CN and PG-OA-10TC for the treatment of pain associated with osteoarthritis of the knee compared to a placebo control assessed by Common Terminology Criteria For Adverse Events (CTCAE) v4.0. | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CBN, Cannabidiol, Cannabinol, THC, CBD, Osteoarthritis, Pain, Placebo