Talk: A Phase 2 Study Evaluating the Acute Pain Relief of a Nano-Formulated Oral Naproxen (2011 ACR/ARHP Annual Scientific Meeting)

Monday, November 7, 2011: 9:00 AM-6:00 PM

Hall F2 - Poster Hall (McCormick Place West)

Garen Manvelian, Iroko Pharmaceuticals, Poway, CA, Stephen Daniels, Premier Research Group, Austin, TX, Allan Gibofsky, Hospital for Special Surgery, New York, NY and Vibeke Strand, Stanford University, Palo Alto, CA

Presentation Number: 1281

Background/Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the relief of a variety of painful rheumatologic and musculoskeletal conditions, despite concerns about the safety and tolerability of this class of drugs. The purpose of this randomized controlled trial was to evaluate the efficacy and safety of an investigational, nano-formulated, oral naproxen when compared with naproxen and placebo in a validated and standardized model of acute pain.

Method: This was a Phase 2, multicenter, randomized, single-dose, active- and placebo-controlled trial. In total, 253 subjects 18-50 years of age were enrolled following extraction of ≥2 third molars (≥1 of which was a fully or partially impacted mandibular third molar) who experienced moderate to severe pain (a score of ≥50 mm on a 100 mm Visual Analogue Scale [VAS]) ≤6 hours after surgery) within 6 hours after surgery. Subjects received nano-formulated naproxen 200 mg or 400 mg, standard naproxen 250 mg or 500 mg, or placebo. The primary efficacy endpoint was the sum of total pain relief (TOTPAR) over 0-12 hours (TOTPAR-12). TOTPAR-8 and TOTPAR-4, secondary efficacy endpoints, were also evaluated along with VAS pain intensity difference (VASSPID).

Result: Nano-formulated naproxen 400 mg and 200 mg was significantly (P<0.001) better than placebo for TOTPAR-12 (Table).

Nano-formulated naproxen 400 mg^a   N=51

Standard Naproxen      500 mg^a   N=51

Nano-formulated naproxen   200 mg^a   N=50

Standard Naproxen      250 mg^a   N=50

Placebo   N=51

TOTPAR-12, mean; SD

31.9; 12.4

28.3; 13.0

25.7; 16.1

24.6; 15.3

9.6; 13.6

TOTPAR-8, mean; SD

21.5; 7.6

19.8; 8.1

17.3; 9.8

16.9; 9.8

6.8; 8.8

TOTPAR-4, mean; SD

10.1; 3.5

9.5; 3.8

8.2; 4.3

8.0; 4.5

3.5; 3.9

^aP<0.001 compared with placebo

SD=standard deviation

Similarly, TOTPAR-4 and TOTPAR-8 values for nano-formulated naproxen 400 mg and 200 mg also demonstrated statistical significance in favor of the active treatments compared with placebo (Table). Additionally, VASSPID values over 4, 8, and 12 hours for each treatment group were significantly (P<0.001) better than placebo. Adverse events were reported in 13 subjects (5.1%): nano-formulated naproxen 400 mg (1, 2%); nano-formulated naproxen 200 mg (0), standard naproxen 500 mg (2, 3.9%), standard naproxen 250 mg (3, 6%), and placebo (7, 13.7%).

Conclusion: An investigational nano-formulated, lower dose, oral naproxen demonstrated efficacy and was well-tolerated in an acute pain model. These Phase 2 study results suggest that use of this nano-formulation could offer treatment of acute pain at a lower dose.

Keywords: clinical trials, nanomedicine, naproxen, nonsteroidal antiinflammatory drugs (NSAIDs) and rheumatoid arthritis, treatment

Disclosure: G. Manvelian, Consultant, 5 ; S. Daniels, Consultant, 5 ; A. Gibofsky, Consultant, 5 ; V. Strand, Consultant, 5 .

1281 - A Phase 2 Study Evaluating the Acute Pain Relief of a Nano-Formulated Oral Naproxen