GOAL: multicenter, open-label, post-marketing study of flavocoxid, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin

Abstract

Objectives:

GOAL (Gauging Osteoarthritis [OA] with Limbrel

*Limbrel is manufactured by Primus Pharmaceuticals, Inc., Scottsdale, AZ, USA.

), an open-label, post-marketing study was performed to determine the overall efficacy and gastrointestinal (GI) tolerability of flavocoxid, a novel, plant-based, anti-inflammatory medication, in a ‘real world’ clinical practice setting. To this end, the study enrolled several unique patient types including nonsteroidal anti-inflammatory drug (NSAID) naïve patients, those who had used NSAIDs in the past, regardless of outcome (positive or negative), and those who had previously taken a gastroprotective medication to improve GI tolerability or continued to take it as a precautionary measure to prevent NSAID-associated GI damage.

Methods:

A total of 1067 individuals at 41 rheumatology practices were enrolled and prescribed flavocoxid, 500 mg b.i.d., for 60 days. The Physician Global Assessment of Disease (PGAD) visual analog scale (VAS) was used as a global measure to assess the signs and symptoms of OA, including joint discomfort, functional stiffness, functional mobility and quality of life. In addition, overall tolerability and upper GI tolerability were assessed by individual questions scored on a 5-part Likert scale. The physicians also monitored any interruption in, or cessation of use of flavocoxid due to a GI issue as well as changes in the use of gastroprotective medications. Adverse event (AE) monitoring was also conducted.

Results:

Of the 1005 patients who completed all follow-up visits, physicians recorded an average improvement in VAS scores from 60.1 ± 18.8 at baseline to 42.5 ± 21.9 at 8 weeks (p < 0.001) in 65.8% of patients. The PGAD VAS noted the most significant improvement in those patients with moderate to severe OA (baseline VAS [0 = least severe, 100 = most severe]: 0–25mm, −3.5 ± 6.9; 26–50 mm, −10.1 ± 17.0; 51–75 mm, −19.3 ± 19.5; 76–100 mm, −29.6 ± 23.6; p < 0.001) and in those patients who were historically non-responders to NSAIDs (40.3 ± 21.1 vs. 66.3 ± 17.7 at baseline; p < 0.001). Patients who had previously responded well to NSAIDs had VAS scores of 42.6 ± 19.8 vs. 58.0 ± 18.0 (p < 0.001) and NSAID naïve subjects showed improvement in VAS scores from 60.5 ± 18.0 at baseline to 46.3 ± 23.7 (p < 0.001). The study recorded a low incidence (∼10%) of AEs reported to physicians and good overall tolerability to flavocoxid. Flavocoxid showed improved upper GI tolerability in almost 50% of previous NSAID users (p < 0.001) and reduced therapy interruption in ∼90% of previous NSAID users with a history of GI-related therapy interruptions (p < 0.0001). Finally, the use of flavocoxid resulted in a >30% reduction in or cessation of the use of gastroprotective medications such as proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2s) in subjects (p < 0.001).

Conclusions:

Within a ‘real world’ clinical rheumatology practice setting, flavocoxid demonstrated significant efficacy in the management of OA in multiple patient types and displayed significant potential for reducing the possibility of adverse GI side-effects and use of gastroprotective agents associated with more traditional OA medications. A limitation of this study was that it was open-label and not rigorously controlled. The large population may compensate for this lack of control.

Key words::

• 5-lipoxygenase
• Cyclooxygenase
• Flavocoxid
• Gastrointestinal
• Limbrel
• Osteoarthritis

Transparency

Declaration of funding

Primus Pharmaceuticals, Inc. was the financial sponsor of this study.

Declaration of financial/other relationships

L.P., B.P.B. and R.M.L. have disclosed that they are employees of, and have stock options with Primus.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors acknowledge the contributions of the investigators of the GOAL Study Cooperative Group: Drs Allen, Aloot, Belhorn, Birkel, Burton, Chatpar, Chaudhary, Docherty, Duby, Eppler, Eudy, Fafalak, Faller, Furmanov, Gonzalez, Harell, Horan, Jones, Kempf, Kirkland, Koziol, Lasichak, Lieberman, Mael, Massey, McLain, Mendez, Meredith, Metyas, Myerson, Oparaeche, Rennie, Rosenberg, Schectman, Scheinost, Sinclair, Soloman, Troum, Vo, Wickersham, Wilson and Wolfe as well as the patients in the study. They also acknowledge Micahel Kristoffersen of PRN Pharmaceutical Research Network LLC, who conducted the statistical data analysis.

This paper was collaboratively written by L. Pillai, B. Burnett and R. Levy, who are employees of Primus. The planning and execution of the study was carried out by the contract research organization, PRN, which also performed the statistical analysis of all data results.

Notes

*Limbrel is manufactured by Primus Pharmaceuticals, Inc., Scottsdale, AZ, USA.

*Limbrel is manufactured by Primus Pharmaceuticals, Inc., Scottsdale, AZ, USA.