NCT03092193

Pharmacogenetic and Pharmacokinetics of Naproxen and Associated Naproxen-esomeprazole

Completed Phase 4 Last updated 3 November 2020

What this trial tests

Phase 4 trial testing Naproxen in Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant in 8 participants. Completed in 1 October 2017.

Timeline

1 March 2017

Primary endpoint
1 October 2017

1 October 2017

Quick facts

Lead sponsor	University of Sao Paulo
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	8
Start date	1 March 2017
Primary completion	1 October 2017
Estimated completion	1 October 2017
Sites	1 location across Brazil

Drugs / interventions tested

• Naproxen (naproxen) — full drug profile →
• Naproxen-esomeprazole — full drug profile →

Conditions studied

• Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant — all drugs for Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant →
• Poor Metabolizer Due to Cytochrome p450 CYP2C19 Variant — all drugs for Poor Metabolizer Due to Cytochrome p450 CYP2C19 Variant →

Sponsor

University of Sao Paulo

Who can join

Adults 18 to 60, any sex, with Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant or Poor Metabolizer Due to Cytochrome p450 CYP2C19 Variant. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The family of cytochrome P450 (CYP) is the most important drug metabolizing enzymes which contributes to the metabolism of a large proportion of drugs in humans. Some CYP450 enzymes reduce or alter the pharmacodynamic activity of many drugs and are involved in oxidative metabolism and elimination of many drugs commonly used by the population. Polymorphisms in CYP2C8 and CYP2C9 are common in different populations around the world and genetic variations in these alleles can cause decreased enzyme activity to nonsteroidal anti-inflammatory drugs (NSAIDs) such as celecoxib, diclofenac, ibuprofen, indomethacin, lornoxicam, meloxicam, valdecoxib, piroxicam, tenoxicam and naproxen. This compromise the bioavailability of the drug can alter the pharmacokinetics of these drugs and patients with mutations in these genes can exhibit increased plasma concentrations of values and areas under the curve (AUC), in addition to decreased clearance of drugs. Associations between NSAIDs and gastric protectors or proton pump inhibitors (PPIs) have become common nowadays, especially in patients who make chronic use of these drugs. Naproxen associated to esomeprazole, a proton pump inhibitor (PPI), was launched in the market recently and its application in acute pain is not yet elucidated. Esomeprazole suffers strong influence of CYP2C19 (hepatic drug-metabolizing enzyme that degrades PPIs). In patients with high enzyme activity of the CYP2C19, the drug can suffer high enzymatic degradation, and its diminished effect. Moreover, in patients with low enzyme CYP2C19 activity, the effect of acid inhibition by PPIs can be very strong.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Simultaneous separation of naproxen and 6-O-desmethylnaproxen metabolite in saliva samples by liquid chromatography-tandem mass spectrometry: Pharmacokinetic study of naproxen alone and associated with esomeprazole.
   Dionísio TJ, Oliveira GM, Morettin M, Faria FC, et al · · 2020 · cited 10× · PMID 32780750 · DOI 10.1371/journal.pone.0236297
2. Simultaneous separation of naproxen and 6-O-desmethylnaproxen metabolite in saliva samples by liquid chromatography-tandem mass spectrometry: Pharmacokinetic study of naproxen alone and associated with esomeprazol-Results.
   Oliveira GM, Dionísio TJ, Polanco NLDH, Siqueira-Sandrin VS, et al · · 2022 · cited 1× · PMID 36454922 · DOI 10.1371/journal.pone.0278411