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

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04992962
• Other study ID #: PG-OA-2021
• Status: Recruiting
• Phase: Phase 2
• Start date: July 29, 2021
• Est. completion date: November 14, 2021

Study information

• Verified date: July 2021
• Source: Pure Green
• Contact: Matthew Caloura
• Phone: (248) 802-4380
• Email: mcaloura[@]pgpharma.co
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: November 14, 2021
• Est. primary completion date: October 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. Subject is at least 21 years of age;

2. Subject has a diagnosis of osteoarthritis of the knee as determined by the subject's primary care physician or related health care provider.

3. Subject reports an average NPRS score of = 5 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 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.

6. 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.

7. Subject has not taken any NSAIDs and/or acetaminophen for at least 2 days prior to starting study treatment.

8. Subject is willing to provide his/her written informed consent to participate in the study as stated in the informed consent document.

9. Subject is willing to use an electronic diary to enter trial information for 29 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 the investigational product;

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 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.

17. Subject has taken a prohibited medication during the screening period and prior to starting study treatment or is unwilling to stop these medications.

18. Subject has an allergy to, or has an intolerance to, NSAIDs or acetaminophen.

19. Subject has taken any form of steroids, including a local steroid injection in the knee, within 1 month of starting study treatment.

20. Subject has received any invasive interventions or surgery of the knee.

21. Subject has a history of substance or alcohol abuse.

22. Subject has clinically significant illness, including cardiovascular disorders.

23. 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.

24. Subject does not have access to a smart phone or does not know how to use a smart phone application.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• CBD/CBN
A water-soluble sublingual tablet containing 10 mg of CBD and 10 mg of CBN.
• CBD/THC
A water-soluble sublingual tablet containing 10 mg of CBD and 5 mg of THC.
• Placebo
An inactive compound.

Locations

Country	Name	City	State
United States	Pure Green Pharmaceuticals	West Bloomfield	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Pure Green

Country where clinical trial is conducted

United States, 

References & Publications (13)

Ahrnsbrak, R., Bose, J., Hedden, S. L., Lipari, R. N., & Park-Lee, E. (2017). Key substance use and mental health indicators in the United States: Results from the 2016 National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, 1572.

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. Epub 2005 Nov 9. — View Citation

Childs JD, Piva SR, Fritz JM. Responsiveness of the numeric pain rating scale in patients with low back pain. Spine (Phila Pa 1976). 2005 Jun 1;30(11):1331-4. — View Citation

Eli Lilly & Company. (2019). Cymbalta: Highlights of prescribing information. Indianapolis, IN.

Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9. — View Citation

Frakes EP, Risser RC, Ball TD, Hochberg MC, Wohlreich MM. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011 Dec;27(12):2361-72. doi: 10.1185/03007995.2011.633502. Epub 2011 Nov 9. Erratum in: Curr Med Res Opin. 2012 May;28(5):822. — View Citation

Jacquet C, Pioger C, Khakha R, Steltzlen C, Kley K, Pujol N, Ollivier M. Evaluation of the "Minimal Clinically Important Difference" (MCID) of the KOOS, KSS and SF-12 scores after open-wedge high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. 2021 Mar;29(3):820-826. doi: 10.1007/s00167-020-06026-0. Epub 2020 Apr 27. — View Citation

Michener LA, Snyder AR, Leggin BG. Responsiveness of the numeric pain rating scale in patients with shoulder pain and the effect of surgical status. J Sport Rehabil. 2011 Feb;20(1):115-28. — View Citation

Ogura T, Ackermann J, Mestriner AB, Merkely G, Gomoll AH. The Minimal Clinically Important Difference and Substantial Clinical Benefit in the Patient-Reported Outcome Measures of Patients Undergoing Osteochondral Allograft Transplantation in the Knee. Cartilage. 2021 Jan;12(1):42-50. doi: 10.1177/1947603518812552. Epub 2018 Nov 22. — View Citation

Papaleontiou M, Henderson CR Jr, Turner BJ, Moore AA, Olkhovskaya Y, Amanfo L, Reid MC. Outcomes associated with opioid use in the treatment of chronic noncancer pain in older adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2010 Jul;58(7):1353-69. doi: 10.1111/j.1532-5415.2010.02920.x. Epub 2010 Jun 1. Review. — View Citation

Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(50-51):1445-1452. doi: 10.15585/mmwr.mm655051e1. — View Citation

Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ. 2008 Jun 17;178(13):1669-78. doi: 10.1503/cmaj.071178. Review. — View Citation

Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355-69. doi: 10.1016/j.cger.2010.03.001. Review. Erratum in: Clin Geriatr Med. 2013 May;29(2):ix. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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