Exploratory Study of PENNSAID Gel to Treat Symptoms of Knee Osteoarthritis

A Phase 2, Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Clinical Study to Evaluate the Safety and Efficacy of PENNSAID Gel in the Symptomatic Treatment of Osteoarthritis of the Knee

Osteoarthritis (OA) is the most common form of arthritis. It can cause pain, swelling, and reduced motion in the joints. That can reduce quality of life.

OA can occur in any joint, but usually affects the hands, knees, hips or spine.

The purpose of this study is to find out if doctors might be able to use 2% PENNSAID gel to treat OA in the knee.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: PENNSAID Gel; Drug: Vehicle

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Genova Clinical Research
  • California
    • Sacramento, California, United States, 95816
      • Benchmark Research
  • Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research, Inc
    • DeLand, Florida, United States, 32724
      • Avail Clinical Research
    • Saint Petersburg, Florida, United States, 33716
      • Comprehensive NeuroScience Inc.
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
    • Savannah, Georgia, United States, 31406
      • South Coast Medical Group
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Clinical Trials Technology, Inc.
  • Kentucky
    • Erlanger, Kentucky, United States, 41018
      • Sterling Research
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research
    • Saint Louis, Missouri, United States, 63141
      • Radiant Research Inc.
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Clinical Study Center of Asheville
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research, LLC
    • Salisbury, North Carolina, United States, 28144
      • Crescent Medical Research
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Medical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research
    • Columbus, Ohio, United States, 43212
      • Radiant Research Inc.
    • Perrysburg, Ohio, United States, 43551
      • Clinical Research Source, Inc.
  • South Carolina
    • Anderson, South Carolina, United States, 29261
      • Radiant Research Inc.
    • Mount Pleasant, South Carolina, United States, 29464
      • Palmetto Medical Research
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group Clinical Research
  • Texas
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research
    • San Angelo, Texas, United States, 76904
      • Benchmark Research
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Roanoke, Virginia, United States, 24018
      • HypotheTest, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Primary osteoarthritis of the knee
2. Radiologic evidence of OA of the knee
3. On stable pain therapy with an oral or topical NSAID or acetaminophen
4. Experience a "moderate flare" of pain following washout of stable pain therapy
5. Able to read and understand English or Spanish to answer pain assessment questions without any explanation
6. If female, surgically sterile or non-pregnant
7. Except for OA, in reasonably good general health
8. Written informed consent

Exclusion Criteria:

1. Secondary OA of the study knee
2. History of pseudo gout or inflammatory flare-ups
3. Participation would conflict with contraindications, warnings or precautions as stated in the prescribing information for oral or topical diclofenac
4. Severe, uncontrolled cardiac, renal, hepatic, or other systemic disease
5. Any malignancy within the previous 3 years, except local therapy for superficial skin cancer not on the study knee
6. Known sensitivity to the use of oral or topical diclofenac, aspirin [acetylsalicylic acid (ASA)] or any other NSAID, dimethyl sulfoxide (DMSO), or ethanol
7. Ongoing abnormality that could confound interpretation of the safety results (eg, anemia, unresponsive gastrointestinal [GI] reflux, etc.)
8. Documented gastroduodenal ulcer or any GI bleeding (except hemorrhoidal) within the last 6 months
9. Uncontrolled diabetes
10. Screening laboratory test results of serum creatinine ≥ 1.5 times upper limit of normal; aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyltransferase (GGT) ≥ 3 times upper limit of normal; and hemoglobin less than or equal to lower limit of normal
11. Documented alcohol or drug abuse within 1 year
12. If female, breast-feeding
13. Major surgery or previous damage to the study knee at any time, or minor knee surgery to the study knee within 1 year
14. Requires oral or intra-muscular corticosteroids, or received an intra articular corticosteroid injection into the study knee within the past 90 days, or into any other joint within the past 30 days, or currently applying topical corticosteroids onto the study knee
15. Received intra-articular viscosupplementation (eg, hylan G-F 20 [Synvisc®]) in the study knee in the past 6 months
16. On prior stable therapy (ie, more than 3 days per week for the previous month) with an opioid analgesic prior to the screening visit will be excluded.
17. Recently started taking a sedative hypnotic medication for insomnia
18. Taking anti-depressants
19. Not willing to discontinue prohibited medications/therapies
20. Cannot tolerate acetaminophen
21. Re-entering study after dropping out or withdrawn from study
22. Used another investigational drug within the previous 30 days
23. On or currently applying for disability benefits on the basis of knee OA
24. History of fibromyalgia
25. Other painful or disabling conditions affecting the knee or leg, or disabling condition of the hands (used to apply the study drug)
26. Skin disorder with current involvement on the hands (used to apply the study drug) or the knee(s) (application site)
27. Referred to an orthopedic surgeon for consideration of, or been advised to have, knee replacement or knee reconstruction surgery
28. Radiologic evidence of OA of the knee advanced to the point that all cartilage has been eroded (ie, bone on bone)
29. Recently started using a cane within the past 30 days
30. History of chronic headaches that may require more than occasional use of rescue medication for headaches

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PENNSAID Gel; Diclofenac sodium 2.0% w/w	Drug: PENNSAID Gel; 2 mL applied to the front, back and sides of the knee twice a day (morning and night) for 4 weeks; Other Names: diclofenac sodium 2.0% w/w
Placebo Comparator: Vehicle; The complete carrier containing ingredients at the same concentrations as experimental arm without diclofenac sodium	Drug: Vehicle; 2 mL applied to the front, back and sides of the knee twice a day (morning and night) for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain When Walking On A Flat Surface	Participants rate their pain intensity when walking on a flat surface as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Baseline
Pain When Walking On A Flat Surface	Participants rate their pain intensity when walking on a flat surface as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Week 4
Pain When Going Up Or Down Stairs	Participants rate their pain intensity when going up or down stairs as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Baseline
Pain When Going Up Or Down Stairs	Participants rate their pain intensity when going up or down stairs as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Week 4
Pain At Night While In Bed	Participants rate their pain intensity at night while in bed as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Baseline
Pain At Night While In Bed	Participants rate their pain intensity at night while in bed as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Week 4
Pain While Sitting Or Lying Down	Participants rate their pain intensity while sitting or lying down as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Baseline
Pain While Sitting Or Lying Down	Participants rate their pain intensity while sitting or lying down as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Week 4
Pain While Standing	Participants rate their pain intensity while standing as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Baseline
Pain While Standing	Participants rate their pain intensity while standing as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.	at Week 4

Collaborators and Investigators

• Sponsor: Mallinckrodt
• Investigators: Study Director: Joseph Pierro, MD, Mallinckrodt

Publications and helpful links

General Publications

• Wadsworth LT, Kent JD, Holt RJ. Efficacy and safety of diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled, 4 week study. Curr Med Res Opin. 2016;32(2):241-50. doi: 10.1185/03007995.2015.1113400. Epub 2015 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2010
• Primary Completion (Actual): February 16, 2011
• Study Completion (Actual): February 16, 2011

Study Registration Dates

• First Submitted: April 28, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (Estimate): May 10, 2010

Study Record Updates

• Last Update Posted (Actual): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Arthritis; Osteoarthritis; Topical NSAID; Diclofenac; NSAIDs; PENNSAID
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: COV05100031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No