Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Osteoarthritis (OA) is a frequent cause of disability in adults. NSAIDs such as diclofenac are often prescribed to treat OA pain. However, NSAIDs are associated with serious dose-related gastrointestinal (GI) and cardiovascular adverse effects, leading the FDA to recommend NSAID use at the lowest dose for the shortest duration necessary to achieve treatment goals. SoluMatrix® diclofenac has been developed using SoluMatrix Fine Particle TechnologyTM to provide efficacy at low doses and is approved for treatment of mild to moderate acute pain in adults. We report results from a 12-month, open-label phase 3 study investigating SoluMatrix diclofenac in patients with OA.
Methods : This multicenter study treated 601 chronic NSAID/acetaminophen users, aged ≥40 years with knee and/or hip OA. Patients initially received SoluMatrix diclofenac 35-mg capsules BID; the dosing regimen could be increased to TID if necessary and subsequently reduced as needed. Safety analyses included incidence of adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and clinical laboratory test results.
Results: Most patients were women (372/601, 61.9%) with a mean (± SD) age of 59.7 ± 8.9 years. Mean (± SD) trial drug administration duration was 274.9 ± 125.7 days. AEs were reported by 451/601 (75.0%) patients (Table). The most frequently reported events included: upper respiratory tract infection (47/601, 7.8%), headache (46/601, 7.7%) and urinary tract infection (44/601, 7.3%). GI ulcer was reported in 1 patient (0.2%), considered related to study medication. Hypertension was reported in 17/601 (2.8%) patients, and serum creatinine increased in 7/601 (1.2%). SAEs were reported in 42/601 (7.0%) patients. Two patients (2/601, 0.3%) experienced myocardial infarction; both considered unrelated to study drug (Table). AEs led to discontinuation in 99/601 (16.1%) patients. Alanine aminotransferase or aspartate aminotransferase ≥3x the upper limit of normal was noted in 20 patients (3.3%), which was associated with elevated bilirubin in one patient and improved following treatment discontinuation.
Conclusion: SoluMatrix diclofenac was generally well tolerated. These data extend the SoluMatrix diclofenac experience to include patients requiring extended treatment for OA pain.
Table.
|
Adverse Event |
SoluMatrix Diclofenac 35 mg TID (n =302)a |
SoluMatrix Diclofenac 35 mg BID (n =601)a,b |
Combined SoluMatrix Diclofenac (n =601)a,c |
|
Most Frequent (>5% in Any Treatment Group) Adverse Events |
|||
|
Any AE |
186 (61.6) |
340 (56.6) |
451 (75.0) |
|
URI |
21 (7.0) |
27 (4.5) |
47 (7.8) |
|
Headache |
11 (3.6) |
36 (6.0) |
46 (7.7) |
|
UTI |
10 (3.3) |
34 (5.7) |
44 (7.3) |
|
Diarrhea |
14 (4.6) |
24 (4.0) |
37 (6.2) |
|
Nasopharyngitis |
11 (3.6) |
24 (4.0) |
34 (5.7) |
|
Nausea |
11 (3.6) |
22 (3.7) |
33 (5.5) |
|
Most Frequent (≥2 Patients) Serious Adverse Events |
|||
|
Any SAE |
15 (5.0) |
26 (4.3) |
42 (7.0) |
|
Osteoarthritis |
1 (0.3) |
2 (0.3) |
3 (0.5) |
|
Carotid artery stenosis |
0 |
2 (0.3) |
2 (0.3) |
|
Chest Pain |
0 |
2 (0.3) |
2 (0.3) |
|
COPD |
0 |
2 (0.3) |
2 (0.3) |
|
Diverticulitis |
1 (0.3) |
1 (0.2) |
2 (0.3) |
|
Lumbar spinal stenosis |
1 (0.3) |
1 (0.2) |
2 (0.3) |
|
Myocardial infarction |
0 |
2 (0.3) |
2 (0.3) |
|
Data presented as n (%). AE = adverse event; BID = twice daily; COPD = chronic obstructive pulmonary disease; SAE = serious adverse event; TID = three times daily; URI=upper respiratory tract infection; UTI = urinary tract infection. aAEs were assigned to the dose regimen the patient received at the AE start date. Post-treatment AEs were assigned to the last dose regimen received. bAll treated patients were included in the SoluMatrix diclofenac twice-daily group for ≥4 days. cAEs with missing start dates and pretreatment AEs are listed in the ‘Combined SoluMatrix Diclofenac’ column.
|
|||
Disclosure:
R. Altman,
Participant in advisory boards for Iroko Pharmaceuticals, consultant to Pfizer, Teva Pharmaceutical Industries Ltd., Petah Tikva, Oletec, Novartis, Johnson & Johnson, consultant and member of the speaker’s bureau for Ferring Pharmaceuticals ,
5;
A. Gibofsky,
Stock shareholder of GlaxoSmithKline plc, Bristol-Myers Squibb, Johnson & Johnson, Amgen, Pfizer, AbbVie, Johnson and Johnson ,
1,
consultant for Takeda, Amgen, AbbVie, UCB Inc., Genentech, Horizon, and Iroko Pharmaceuticals LLC,
5;
M. C. Hochberg,
Iroko Pharmaceuticals LLC, Amgen, AstraZeneca, Covidien, Eli Lilly, EMD Serono, Genentech/Roche, Merck & Co, Inc., Novartis Pharma AG, Pfizer, and Pozen.,
5;
B. Cryer,
: Consulting fees received from Ritter Pharmaceuticals, Sanofi, Sandoz, Sucempo, and Iroko Pharmaceuticals, LLC,
5;
A. J. Kivitz,
None;
V. Strand,
Consultant for AbbVie, Afferent, Amgen, Biogen Idec, Bioventus, BMS, Carbylan, Celgene, Celltrion, CORRONA, Crescendo, Genentech/Roche, GSK, Hospira, Iroko, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, SKK, Takeda, UCB, Vertex,
5;
O. Imasogie,
IBoko Pharmaceuticals LLC,
3;
C. Young,
Iroko Pharmaceuticals, LLC,
3.
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