324 CG100649, A TISSUE-SPECIFIC DUAL INHIBITOR OF COX-2 AND CARBONIC ANHYDRASE: PHASE 2A CLINICAL TRIAL IN HIP &amp; KNEE OSTEOARTHRITIS

Schmidt, W.; Lehnhardt, Klaus; Hettwer, J.; Nadashkevich, Oleh; Szombati, István; Povoroznyuk, Vladyslav; Chung, Bo Young; Nam, Hae Yun; Cho, S.S.; Ro, Shpits; Cho, J.M.

doi:10.1016/s1063-4584(09)60346-0

Cited by 5 publications

(10 citation statements)

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“…This drug behavior supports a dosing schedule of loading and maintenance doses of CG100649 to attain stable steady‐state concentrations. Here, the projected concentration‐time curves of CG100649 (simulations not shown) appear to align well with in vivo data available from male patients with primary osteoarthritis . Nevertheless, a common sentiment is to apply caution when projecting these estimates in the design of subsequent studies.…”

Section: Discussionsupporting

confidence: 60%

“…Here, the projected concentrationtime curves of CG100649 (simulations not shown) appear to align well with in vivo data available from male patients with primary osteoarthritis. 24 Nevertheless, a common sentiment is to apply caution when projecting these estimates in the design of subsequent studies. The parameter estimates might not be entirely representative of the target population since the sample size of the present study is small and since the study enrolled a homogeneous population, healthy volunteers only.…”

Section: Discussionmentioning

confidence: 99%

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GCG100649, A Novel Cyclooxygenase‐2 Inhibitor, Exhibits a Drug Disposition Profile in Healthy Volunteers Compatible With High Affinity to Carbonic Anhydrase‐I/II: Preliminary Dose–Exposure Relationships to Define Clinical Development Strategies

Hirankarn

Barrett

Alamuddin

et al. 2013

Clinical Pharm in Drug Dev

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CG100649, proposed as a dual inhibitor of cyclooxygenase (COX)-2 and carbonic anhydrase (CA)-I/-II, is long-lived in plasma and whole blood. The mean ± SD half-lives were 131 ± 19 and 127 ± 33 hours, respectively, after administration of oral single doses of 2 or 8 mg CG100649 to healthy volunteers. The whole blood to plasma concentration ratio (78 ± 23) for CG100649 is linear over the dosing interval reflecting a biodistribution pattern consistent with other strong CA-inhibitors (e.g., acetazolamide, methazolamide). A one compartment model with first order absorption and elimination described CG100649 concentration-time profiles well. Estimates (%relative SD) between plasma and whole blood were in agreement for the absorption rate constant, 1.54 (58.6) and 1.43 (28.0) hour(-1) , respectively, but considerably different for clearance, 3.29 (10.4) and 0.04 (7.7) L/h/70 kg, and for volume of distribution, 559 (6.7) and 7.6 (2.4) L/70 kg, respectively. The extent to which these unique PK characteristics of CG100649 discriminate it from other COX-2 inhibitors will be the subject of future investigation.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

GCG100649, A Novel Cyclooxygenase‐2 Inhibitor, Exhibits a Drug Disposition Profile in Healthy Volunteers Compatible With High Affinity to Carbonic Anhydrase‐I/II: Preliminary Dose–Exposure Relationships to Define Clinical Development Strategies

Hirankarn

Barrett

Alamuddin

et al. 2013

Clinical Pharm in Drug Dev

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“…This review focuses on the recently approved NSAID in India, polmacoxib. Polmacoxib is currently being marketed in South Korea and India [6][7][8].…”

Section: Burden Of Osteoarthritismentioning

confidence: 99%

“…Polmacoxib was first approved in South Korea in 2015 for the treatment of colorectal cancer and osteoarthritis. It is a first-in-class NSAID with a dual inhibitory action on COX-2 and carbonic anhydrase (CA) enzymes (Figure 1) [6][7][8][9][10][11][12]. Polmacoxib (2 mg) received approval from the Drug Controller General of India on February 14, 2023, for the treatment of idiopathic primary osteoarthritis of the hip and knee [8].…”

Section: Review Polmacoxibmentioning

confidence: 99%

Polmacoxib: A Review of the Newer Non-steroidal Anti-inflammatory Drug in Osteoarthritis

Easwaran,

Mistry,

Bhole

et al. 2024

Cureus

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Osteoarthritis represents a huge socioeconomic burden and has a significant impact on daily life and productivity. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the management of osteoarthritis to curb inflammation, pain, and stiffness and improve physical function. However, due to the various side effects, most healthcare professionals avoid using NSAIDs for a long period. Nonselective cyclooxygenase (COX) inhibitors and cyclooxygenase-1 (COX-1) inhibitors are associated with increased gastrointestinal adverse effects due to the inhibition of prostaglandins, which are responsible for protecting the gastric mucosa. Cyclooxygenase-2 (COX-2) inhibitors are associated with an increased incidence of adverse cardiovascular effects due to their COX-2 inhibitory activity in the circulatory system. Therefore, there is a need for a newer NSAID that has a better safety profile to be used in osteoarthritis. Polmacoxib is a new, orally active, first-in-class NSAID that is a dual inhibitor of COX-2 and carbonic anhydrase (CA). The dual mode of action exhibited by polmacoxib is expected to minimize adverse cardiovascular effects while achieving maximum effectiveness in inflamed osteoarthritic joints. This article aims to review the pharmacological properties, clinical efficacy, and safety data of polmacoxib in osteoarthritis.

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“…Recently, a new COX-2 inhibitor, polmacoxib (CG100649; Acelex), has been developed. 13 14) Unlike other NSAIDs, polmacoxib has a dual mode of action: inhibition of COX-2 and binding to carbonic anhydrase (CA) with high affinity. 15) A key function of CA is to regulate the pH level in the body through the interconversion between carbon dioxide and bicarbonate.…”

mentioning

confidence: 99%

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis

et al. 2017

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BackgroundThe aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA).MethodsThis study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations.ResultsAfter 6 weeks, the polmacoxib-placebo treatment difference was −2.5 (95% confidence interval [CI], −4.4 to −0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, −0.9 to 2.2; p = 0.425). According to Physician's Global Assessments, more subjects were “much improved” at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo.ConclusionsPolmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.

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324 CG100649, A TISSUE-SPECIFIC DUAL INHIBITOR OF COX-2 AND CARBONIC ANHYDRASE: PHASE 2A CLINICAL TRIAL IN HIP & KNEE OSTEOARTHRITIS

Cited by 5 publications

References 0 publications

GCG100649, A Novel Cyclooxygenase‐2 Inhibitor, Exhibits a Drug Disposition Profile in Healthy Volunteers Compatible With High Affinity to Carbonic Anhydrase‐I/II: Preliminary Dose–Exposure Relationships to Define Clinical Development Strategies

GCG100649, A Novel Cyclooxygenase‐2 Inhibitor, Exhibits a Drug Disposition Profile in Healthy Volunteers Compatible With High Affinity to Carbonic Anhydrase‐I/II: Preliminary Dose–Exposure Relationships to Define Clinical Development Strategies

Polmacoxib: A Review of the Newer Non-steroidal Anti-inflammatory Drug in Osteoarthritis

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis

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