A Phase 2 Study of Lower-dose, Indomethacin Submicron Particle Capsules Demonstrates Early Onset of Acute Pain Relief

Manvelian, Garen; Hochberg, Marc C.; Daniels, Stephen E.; Altman, Roy D.; Young, Clarence L.

doi:10.1097/ajp.0000000000000053

Cited by 9 publications

(5 citation statements)

References 16 publications

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“…17 In a phase 2 study of patients following third-molar extraction, indomethacin submicron particle capsules (20 and 40 mg) produced better patient pain relief during a 12-hour study period than placebo. 18 The numbers and types of patient AEs in this study were consistent with similar studies of patients who underwent bunionectomy. 16,19,20 The slightly higher percentage of patients who developed headaches in the indomethacin submicron particle capsule groups is consistent with the well-known safety profile of the drug.…”

supporting

confidence: 83%

“…Phase 1 and phase 2 clinical studies evaluated the pharmacokinetic characteristics and analgesic potential of indomethacin submicron particle capsules in healthy subjects and/or patients with pain following the extraction of impacted third molars 17,18 ; this phase 3 study adds to these published studies. In the phase 1 study in healthy patients, lower-dose indomethacin submicron particle capsules achieved comparable peak plasma levels, shortened the time to peak plasma levels, and reduced overall systemic drug exposure compared with higher-dose commercially available indomethacin capsules.…”

mentioning

confidence: 96%

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Indomethacin Submicron Particle Capsules Provide Effective Pain Relief in Patients with Acute Pain: A Phase 3 Study

Altman

Daniels

Young³

2013

The Physician and Sportsmedicine

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Although frequently prescribed to relieve acute pain in patients, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with dose-related gastrointestinal, cardiovascular, and renal complications. Investigational, submicron particle NSAIDs are being developed that could provide effective pain relief at lower doses than currently available oral NSAIDs. This is the first phase 3 study evaluating the analgesic efficacy and safety of lower-dose indomethacin submicron particle capsules in patients following elective surgery. This multicenter, double-blind study enrolled patients aged 18 to 68 years who underwent bunionectomy under regional anesthesia. Patients with a pain intensity rating of ≥40 mm on a 100-mm Visual Analog Scale were randomized to receive indomethacin submicron particle capsules (40 mg 3 times daily [TID], 40 mg twice daily [BID], or 20 mg TID), celecoxib (400 mg loading dose, then 200 mg BID), or placebo. The primary efficacy parameter was the overall (summed) pain intensity difference measured by a Visual Analog Scale during a period of 48 hours. Scheduled assessments measured secondary efficacy parameters such as patient pain intensity differences. Indomethacin submicron particle capsules 40 mg 3 times daily (509.6 ± 91.9 overall [summed] pain intensity difference), 40 mg twice daily (328.0 ± 92.9 overall [summed] pain intensity difference), and 20 mg 3 times daily (380.5 ± 92.9 overall [summed] pain intensity difference) reduced pain intensity from 0 to 48 hours (P ≤ 0.046 for all 3 groups) compared with placebo (67.8 ± 91.4 overall [summed] pain intensity difference). There was some evidence of patient analgesia for celecoxib (279.4 ± 91.9 overall [summed] pain intensity difference; P = 0.103). Some evidence of pain control was observed in patients as early as 2 hours following administration of indomethacin submicron particle capsules and was sustained throughout the treatment period. Indomethacin submicron particle capsules were generally well tolerated by patients. These results suggest that lower-dose indomethacin submicron particle capsules are a potentially promising treatment option for patients with acute pain.

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supporting

confidence: 83%

mentioning

confidence: 96%

Indomethacin Submicron Particle Capsules Provide Effective Pain Relief in Patients with Acute Pain: A Phase 3 Study

Altman

Daniels

Young³

2013

The Physician and Sportsmedicine

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“…Similarly diclofenac submicron particle capsules have been developed using Solu Matrix technology to provide analgesia at lower doses than available solid oral dosing forms. Better pain control was noted across all active treatment groups at 5 hours and pain relief was sustained throughout the treatment period [98]. On similar lines, indomethacin submicron capsules are well tolerated by patients and are a potentially promising treatment option for patients with acute pain [99].…”

Section: Gastric Ulcer Studiesmentioning

confidence: 76%

Potential Oral Protective Effects of SNEDDS of Diclofenac Sodium on Experimental Gastric Ulcers in Rats

Kumar¹

2018

Biochem Pharmacol

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The Self Nano Emulsifying Drug Delivery Systems (SNEDDS) have gained considerable interest over the past decade for their use in various applications. They have been shown to increase bioavailability and decrease side effects of highly toxic drugs. Non-Steroidal Anti-inflammatory Drugs (NSAIDS) such as Diclofenac Sodium (DFS) lead to major side effect gastric toxicity. The aim of this study was to formulate, characterize and evaluate DFS entrapped SNEDDS. SNEDDS were prepared by emulsion diffusion evaporation technique. DFS formulated SNEDDS showed the least size of 101 ± 3.5 nm, zeta potential of -18.5 ± 1.6 mv and entrapment efficiency of 90.6 ± 2.1 in FESIF respectively. The initial drug release was rapid in FASIF followed by phosphate buffer and the total drug release was high i.e; 74.18% in FASIF followed by phosphate buffer i.e; 70.14%. The drug released for 3-4 hrs approximately in all the media for 50% of release to occur except in SGF and FASGF in which the total percent release itself was 50% till 30 h. A significant reduction in toxicity of DFS was observed for SNEDDS in gastric mucosa when compared to free DFS with a 10 fold decrease in ulcer index of DFS in acute study and a 6.5 fold decrease in ulcer index of DFS in chronic study.

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“…In a phase 2 study in patients experiencing moderate to severe pain following extraction of multiple third molars, the early-development formulation of submicron indomethacin 20 or 40 mg provided significantly better mean total pain relief over 0 to 8 hours than placebo (P < 0.001). Submicron indomethacin promoted earlier onset of analgesia compared with placebo, and was well tolerated [21].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and safety of low-dose submicron indomethacin 20 and 40 mg compared with indomethacin 50 mg

Olugemo

Solorio²,

Sheridan³

et al. 2015

Postgraduate Medicine

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Compared with indomethacin 50 mg, submicron indomethacin 40 mg achieved similar peak plasma concentrations, lower systemic exposure, and a faster time to peak plasma concentration, indicating rapid absorption. The current formulation of low-dose submicron indomethacin has recently demonstrated efficacy in 2 phase 3 studies in patients with acute pain following bunionectomy and represents a new, low-dose treatment option for patients with acute pain.

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A Phase 2 Study of Lower-dose, Indomethacin Submicron Particle Capsules Demonstrates Early Onset of Acute Pain Relief

Abstract: Lower-dose, indomethacin submicron particle capsules provide good overall pain relief in patients with postsurgical pain and are generally well tolerated. Indomethacin submicron particle capsules are a potentially promising option for treatment of acute pain and warrant further study.

Cited by 9 publications

References 16 publications

Indomethacin Submicron Particle Capsules Provide Effective Pain Relief in Patients with Acute Pain: A Phase 3 Study

Indomethacin Submicron Particle Capsules Provide Effective Pain Relief in Patients with Acute Pain: A Phase 3 Study

Potential Oral Protective Effects of SNEDDS of Diclofenac Sodium on Experimental Gastric Ulcers in Rats

Pharmacokinetics and safety of low-dose submicron indomethacin 20 and 40 mg compared with indomethacin 50 mg

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