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Influence of Genotype of CYP2C9 on Clinical Efficacy and Pharmacokinetics of Piroxicam After Lower Third Molar Surgery

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ClinicalTrials.gov Identifier: NCT02450487
Recruitment Status : Completed
First Posted : May 21, 2015
Last Update Posted : December 2, 2015
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Adriana Maria Calvo, University of Sao Paulo

Brief Summary:
Pharmacogenetics is an area of Pharmacology that studies the contribution of genetic factors to individual responses to drugs. This branch of science involves the variability in pharmacodynamics and pharmacokinetics through the study of polymorphisms in genes encoding receptors, as well as in drug metabolism, where this area of Pharmacology has been growing and achieving its first results with clinical use. The non-steroidal anti-inflammatory (NSAIDS) are metabolized by cytochrome P450 (CYP) family, predominantly CYP2C9. The goal of this study is to evaluate the different gene haplotypes for the clinical efficacy of piroxicam after third lower molar surgery for pain, edema and trismus, adverse reactions, need of rescue medication, patient satisfaction regarding the drug and the pharmacokinetics of the drug between the different gene haplotypes for CYP2C9 that are found in this population. Therefore, 60 patients will be genotyped and phenotyped for this gene and their postoperative data will be confronted with the data found in the Brazilian population. For the analysis of the proposed gene, saliva will be collected and serve as a source of genomic DNA. For the molecular analysis, polymerase chain reaction (PCR) with tests validated and produced by Applied Biosystems® will be performed. For the pharmacokinetics, saliva samples will be collected at various times according to protocols available in the literature, and piroxicam concentrations in the samples will be measured by high pressure liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC MS/MS). The analysis of the results will be described with a significance level of 0.05.

Condition or disease Intervention/treatment Phase
Pain Other Surgical Procedures Impacted Third Molar Tooth Cytochrome P450 CYP2C9 Enzyme Deficiency Drug: Piroxicam Phase 4

Detailed Description:

Lower third molars (with high degree of difficulty) surgeries will be performed in Clinical Pharmacology Laboratory at the Bauru School of Dentistry - University of São Paulo (FOB-USP), which will be provided to patients daily doses of piroxicam 20 mg 4 days. Thus collect data related to pain, swelling, trismus, amount of rescue medication required by patients, overall assessment and satisfaction about taking medicine, saliva samples for the analysis of the pharmacokinetics of the drug, genotyping and phenotyping of the subjects of the research.

The global clinical evaluation along with genotyping and phenotyping these individuals can show us if there is an influence not only in adverse effects, but also in the therapeutic effects of the drug in the Brazilian population. Research of this nature are rare in this area of Clinical Pharmacogenetics and can be of great help in prescribing these drugs to control pain and inflammation.After the removal of third molars will make collecting 6 mL of saliva in several post-surgical moments for analysis of the pharmacokinetics of the drug piroxicam and 10 mL of saliva for the analysis of genetic material. It is noteworthy that this project will initiate the nucleation of a new line of research in college, the first in Pharmacogenetics area conducted in FOB / USP.Will be assessed the following parameters in all patients after surgery of at least a third lower molar with a high degree of difficulty (Annexes 1, 2 and 3): 1) onset and duration of surgery after the administration of the local anesthetic, 2) open mouth prior to surgery, on the 2nd day after the surgery and on the 7th day after surgery (removal of stitches); 3) measured the facial edema in the second day after surgery and on the 7th day after surgery (compared to the measurements obtained before surgery); 4) body temperature before surgery, on the 2nd day after the operation and on the 7th day after surgery (removal of stitches); 5) incidence, type and severity of adverse reactions, 6) plug pain (VAS - visual analog scale) filled by patients for 4 days after prescription Piroxicam; 7) amount of rescue medication required by patients.

The comparative analysis of the data, along with data on the pharmacokinetics of the drug, genotyping and phenotyping the CYP2C9 gene, provide the basis for evaluation of the influence of the gene in clinical efficacy, side effects and need for relief medication required by patients after surgery third- molars with a high degree of difficulty, which was prescribed as anti-inflammatory piroxicam.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 102 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Influence of Genotype of Cytochrome P450 (CYP2C9) on Clinical Efficacy and Pharmacokinetics of Piroxicam After Lower Third Molar Surgery
Study Start Date : October 2012
Actual Primary Completion Date : October 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Piroxicam

Arm Intervention/treatment
Experimental: Interventional group
100 patients will be treated with Piroxicam (20 mg once daily for 4 days) for pain control after lower third molar surgery
Drug: Piroxicam
After extraction of at least one third molar, 100 patients will be treated with Piroxicam (20 mg once daily for 4 days) for pain control, collect the saliva to be genotyped and phenotyped for CYP2C9 (by PCR) and their post-operative notes (pain, swelling, trismus, temperature) will be analyzed. For the pharmacokinetics of piroxicam saliva samples will be collected from 10 of these patients at different times after ingestion of a capsule of 20 mg Piroxicam (before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72 hours after ingestion).
Other Names:
  • Lower third molar surgery
  • Pharmacogenetics




Primary Outcome Measures :
  1. Reduction of pain measured by visual analogue scale [ Time Frame: Seven days after surgery ]
    Reducing pain after third molar surgery is measured by visual analogue scale. It is expected that the visual analogue scale 100mm present lower values in patients heterozygous and mutated for the CYP2C9 the evaluated periods of 0, 15, 30,45 min, 1, 2, 3, 4, 5, 6, 8, 12, 16 , 24 48 and 72 hours after surgery.


Secondary Outcome Measures :
  1. Adverse effects [ Time Frame: Seven days after surgery ]
    Increased reporting of adverse effects during the postoperative period until suture removal seven days after extraction of third molar included and/or impacted in patients heterozygous or mutated for CYP2C9 assessed by the information contained in the medical records of the patient.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Impacted lower third molar;
  • not making use of nonsteroidal anti-inflammatory drugs in the last 7 days;

Exclusion Criteria:

  • Local anesthetics allergy;
  • History of gastrointestinal bleeding or ulcers;
  • Kidney disease;
  • Asthma;
  • Allergy or sensitivity to aspirin or any other anti-inflammatory non-steroid agent;
  • Pregnant or nursing women;
  • Patients using antidepressant, diuretic or aspirin;
  • Patients received antibiotics for 30 days prior to surgery.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02450487


Sponsors and Collaborators
University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
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Study Chair: Adriana M Calvo, PhD Bauru School of Dentistry/University of Sao Paulo

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Responsible Party: Adriana Maria Calvo, PhD DDS, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT02450487    
Other Study ID Numbers: 20657913.7.0000.5417 CAAE
First Posted: May 21, 2015    Key Record Dates
Last Update Posted: December 2, 2015
Last Verified: December 2015
Keywords provided by Adriana Maria Calvo, University of Sao Paulo:
Piroxicam
Pharmacogenetic
Lower Third molar
Additional relevant MeSH terms:
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Tooth, Impacted
Tooth Diseases
Stomatognathic Diseases
Piroxicam
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action