Osteoarthritis of the Knee Pain Study Using a CBD and THC Sublingual Tablet

• ClinicalTrials.gov Identifier: NCT04195269
• Recruitment Status: Unknown
• First Posted: December 11, 2019
• Last Update Posted: April 14, 2020
• Sponsor: Pure Green
• Information provided by (Responsible Party): Pure Green

Study Description

Brief Summary:

This study is a prospective Phase 2, drug controlled, open-label study to evaluate the safety and efficacy of Pure Green sublingual tablets for the treatment of pain associated with osteoarthritis of the knee.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee; Pain	Drug: Test Article	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Osteoarthritis of the Knee Pain Study Using CBD and THC in Rapidly Dissolvable Sublingual Tablet
• Estimated Study Start Date: April 20, 2020
• Estimated Primary Completion Date: June 30, 2020
• Estimated Study Completion Date: July 15, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pure Green Sublingual Tablet - Daily; Subjects will take 2 tablets daily, one in the morning and one in the evening, and are able to take up to 2 additional tablets per day as needed for pain.	Drug: Test Article; 10 mg CBD, 10 mg of THC, and a proprietary blend of terpenes.

Outcome Measures

Primary Outcome Measures :

1. Impact of Pure Green sublingual tablets on pain due to osteoarthritis of the knee using a daily self-reported pain scale score. [ Time Frame: 30 days ]
   To evaluate the safety and efficacy of Pure Green sublingual tablets for the treatment of pain due to osteoarthritis of the knee by having patients evaluate their daily pain scale score reported as 0-10 where 0 is no pain and 10 is the worst pain possible as self-reported with every dose taken by the patient in the smart phone app. The objective is to reduce the patients average daily pain scale score to less than 4.

Secondary Outcome Measures :

1. Impact of Pure Green sublingual tablets on general health and well-being of Osteoarthritis of the knee patients. [ Time Frame: 30 Days ]
   To evaluate the impact of Pure Green sublingual tablets on the general health and well-being of osteoarthritis of the knee patiens. The objective is to examine quality of life metrics: overall quality of life and general health, physical health, and knee pain as measured on a 1-5 scale before and after the study
2. Impact of Pure Green sublingual tablets on sleep improvement of patients with osteoarthritis of the knee. [ Time Frame: 30 Days ]
   The Pittsburgh Sleep Quality Index will be used to compare pre and post Pure Green sublingual tablet study on sleep changes. Patients will be asked questions before beginning of the study and after completion.
3. Impact of Pure Green sublingual tablets on anxiety of patients with osteoarthritis if the knee [ Time Frame: 30 Days ]
   The Hamilton Anxiety rating scale questionnaire will be administered before the study begins and after completion to examine the impact of Pure Green sublingual tablets on anxiety in patients with osteoarthritis of the knee. The scale of 0-4 will be used where 0 is no anxiety present and 4 is very severe anxiety.
4. Impact on the use of sublingual tablets as the route of administration. [ Time Frame: 30 Days ]
   To explore the impact of sublingual administration on patient compliance by evaluating the number of tablets taken per day as entered by the patients into the smart phone app.

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subject is at least 21 years of age;
2. Subject has a diagnosis of a pain related to osteoarthritis of the knee as determined by the subject's primary care physician or related health care provider.
3. Subject has a mean pain scale score of ≥ 4 recorded in the 7 days prior to enrollment.
4. 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.
5. 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 promises 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.
6. Subject has not taken any pain medication, including NSAIDs, for at least 2 days before taking the first dose of study drug.
7. Subject is willing to provide his/her written informed consent to participate in the study as stated in the informed consent document.
8. Subject is willing to use an electronic diary to enter a pain scale score up to four times a day for 28 days.

Exclusion Criteria

1. Subject is pregnant or lactating;
2. Subject has an allergy to cannabis, the Cannabaceae plant family (e.g., hemp, hops), palmitoylethanolamide, or terpenes;
3. Subject has a known allergy to active or inert ingredients of PG-OA-10:10-2020-B tablets;
4. 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));
5. 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;
6. Subject is currently being treated with antibiotics for sinus, throat, or lung infections;
7. Subject has shortness of breath associated with allergies;
8. Subject has uncontrolled asthma;
9. Subject has a fever and/or productive cough;
10. Subject has unstable angina, uncontrolled hypertension;
11. Subject currently or has a history of congestive heart failure;
12. Subject has any other unstable medical condition;
13. Subject has a personal or family history of schizophrenia;
14. Subject has a personal history or currently has suicidal ideation or attempted suicide;
15. Subject has a major neurological disorder, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain injury/head injury, and seizures.
16. Subject has taken pain medicine of any kind throughout the screening period, or has taken acetaminophen within 2 days of taking the first dose of study drug.
17. Subject has an allergy to, or has an intolerance to, acetaminophen.
18. Subject is currently taking any form of opioids.
19. Subject has a history of alcohol or substance abuse
20. Subject has clinically significant illness, including cardiovascular disorders.
21. 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.
22. Subject does not have access to a smart phone or does not know how to use a smart phone application.

Contacts and Locations

Contacts

Contact: Matthew Caloura, C.C.R.P.; (248) 802-4380; mcaloura@pure.green

Locations

United States, Michigan

Pure Green, LLC; Recruiting

West Bloomfield, Michigan, United States, 48323

Contact: Matthew Caloura 248-802-4380 mcaloura@pure.green

Sponsors and Collaborators

Pure Green

Investigators

• Principal Investigator: Debra Kimless, M.D.; Chief Medical Officer

More Information

Publications:

Brown JP, Boulay LJ. Clinical experience with duloxetine in the management of chronic musculoskeletal pain. A focus on osteoarthritis of the knee. Ther Adv Musculoskelet Dis. 2013 Dec;5(6):291-304. doi: 10.1177/1759720X13508508.

Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006 Jan;45(1):50-2. doi: 10.1093/rheumatology/kei183. Epub 2005 Nov 9.

Australian Public Assessment Report for Nabiximols

O'Brien M, McDougall JJ. Cannabis and joints: scientific evidence for the alleviation of osteoarthritis pain by cannabinoids. Curr Opin Pharmacol. 2018 Jun;40:104-109. doi: 10.1016/j.coph.2018.03.012. Epub 2018 Apr 7.

Huggins JP, Smart TS, Langman S, Taylor L, Young T. An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain. 2012 Sep;153(9):1837-1846. doi: 10.1016/j.pain.2012.04.020. Epub 2012 Jun 21.

Fukuda S, Kohsaka H, Takayasu A, Yokoyama W, Miyabe C, Miyabe Y, Harigai M, Miyasaka N, Nanki T. Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis. BMC Musculoskelet Disord. 2014 Aug 12;15:275. doi: 10.1186/1471-2474-15-275.

Krustev E, Reid A, McDougall JJ. Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints. Arthritis Res Ther. 2014 Sep 27;16(5):437. doi: 10.1186/s13075-014-0437-9.

Smith FL, Fujimori K, Lowe J, Welch SP. Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in nonarthritic and arthritic rats. Pharmacol Biochem Behav. 1998 May;60(1):183-91. doi: 10.1016/s0091-3057(97)00583-2.

Schuelert N, McDougall JJ. Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 2008 Jan;58(1):145-53. doi: 10.1002/art.23156.

Schuelert N, Johnson MP, Oskins JL, Jassal K, Chambers MG, McDougall JJ. Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain. 2011 May;152(5):975-981. doi: 10.1016/j.pain.2010.11.025. Epub 2010 Dec 24.

Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, Kendall DA, Scammell BE, Reeve AJ, Chapman V. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008;10(2):R43. doi: 10.1186/ar2401. Epub 2008 Apr 16.

• Responsible Party: Pure Green
• ClinicalTrials.gov Identifier: NCT04195269
• Other Study ID Numbers: PG-OA-1010-19-004
• First Posted: December 11, 2019
• Last Update Posted: April 14, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pure Green:

CBD; THC; Cannabidiol; Tetrahydrocannabinol; Osteoarthritis; Knee; Pain

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases