Rapid Screening Phenotype Test To Evaluate CYP 2C19 Enzyme Activity Using Stable Isotope [13C]Pantoprazole

NCT00668902 | Completed Results DMC

• 1 other identifier: 0611-07
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the function of an enzyme that breaks down drugs and helps the removal of drugs from your body. This enzyme is called cytochrome P450 2C19 and is located in your liver. Exposure to other medications or variations in genes that you have inherited from your parents, may speed up or slow the function of this enzyme. As a result, some patients may develop unwanted effects from a drug while some other patients may not get benefit from taking the same drug. The aim of this study is to determine the function of this enzyme in your liver. We will do this by performing a series of breath tests and blood samples after you take pantoprazole. Pantoprazole is approved as an oral and intravenous drug by the Food and Drug Administration (FDA).

Conditions

Healthy

Keywords

CYP2C19; Pantoprazole; Genotype; Pharmacokinetics; Metabolism

Outcome Measures

Primary Outcomes (1)

• DOBmax (Maximum Value of DOB)

  The stable isotope \[13C\]pantoprazole is O-demethylated by cytochrome P450 CYP2C19 and that the 13CO2 produced and exhaled in breath as a result can serve as a safe, rapid, and noninvasive phenotyping marker of CYP2C19 activity in vivo. Exhaled 13CO2 and 12CO2 were measured by IR spectroscopy before (baseline) and 2.5 to 120 min after dosing. Ratios of 13CO2/12CO2 after \[13C\]pantoprazole relative to 13CO2/12CO2 at baseline were expressed as change over baseline (DOB).

  baseline and 2.5, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min after dosing

Study Arms (3)

EM of CYP2C19

EXPERIMENTAL

CYP2C19 enzyme activity in extensive metabolizers of CYP2C19 (CYP2C19\*1/\*1 genotype, or wild type) was measured by 13C)Pantoprazole breath test.

Drug: [13C]Pantoprazole

IM of CYP2C19

EXPERIMENTAL

CYP2C19 activity in heterozygous for deficient CYP2C19 alleles (\*2 and \*3, IM of CYP2C19) was measured by (13C)Pantoprazole breath test.

Drug: [13C]Pantoprazole

PM of CYP2C19

EXPERIMENTAL

Homozygous for CYP2C19 null alleles (\*2/\*2, \*2/\*3 or \*3/\*3, Poor metabolizers) was measured by (13C)Pantoprazole breath test.

Drug: [13C]Pantoprazole

Interventions

[13C]Pantoprazole DRUG

\[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes

Also known as: Breath test

EM of CYP2C19; IM of CYP2C19; PM of CYP2C19

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Asian male or female subjects between 18 and 49 years of age, who are in good physical health with no significant medical problems or laboratory test abnormalities. Subjects should have normal liver and kidney function.
• Subjects with BMI \<30 which will be determined by Metropolitan height and weight tables. Subjects must weigh at least 110 pounds.
• Subjects must agree to refrain from taking any prescription and over-the-counter medications, as well as any herbal medications one week before the start of the study and during the study period.
• Subjects must agree to refrain from consuming alcohol 48 hours before the start of the study and during the study period.
• Subjects must be capable of satisfying protocol requirements and be able to sign written informed consent.

You may not qualify if:

• Subjects who have a history of intolerance or allergy to the study drug: pantoprazole.
• Subjects who have donated blood within the last 60 days of the screening visit or plan to donate blood during the course of the study or within 60 days after study completion.
• Subjects who have had treatment with any investigational drug within the past 30 days.
• Subjects who have used illegal drugs within three months prior to enrollment.
• Female subjects currently taking oral contraceptive birth control pills and who are unwilling or unable to stop oral contraceptives and use a barrier contraceptive method (such as condom, contraceptive foams, etc.) starting from the time of screening phase to the completion of the study.
• Female subjects who are pregnant or lactating.
• Subjects who are unreliable in the opinion of the study physician.

Sponsors & Collaborators

• Indiana University: lead
• Sponsor Name Pending: collaborator

Study Sites (1)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Related Publications (8)

• Desta Z, Zhao X, Shin JG, Flockhart DA. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet. 2002;41(12):913-58. doi: 10.2165/00003088-200241120-00002.

  PMID: 12222994 BACKGROUND

• Goldstein JA. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol. 2001 Oct;52(4):349-55. doi: 10.1046/j.0306-5251.2001.01499.x.

  PMID: 11678778 BACKGROUND

• De Morais SM, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol. 1994 Oct;46(4):594-8.

  PMID: 7969038 BACKGROUND

• de Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994 Jun 3;269(22):15419-22.

  PMID: 8195181 BACKGROUND

• Ibeanu GC, Blaisdell J, Ghanayem BI, Beyeler C, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Daly AK, Goldstein JA. An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics. 1998 Apr;8(2):129-35. doi: 10.1097/00008571-199804000-00006.

  PMID: 10022751 BACKGROUND

• Ibeanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer P, Ghanayem BI, Blaisdell J. Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998 Sep;286(3):1490-5.

  PMID: 9732415 BACKGROUND

• Ferguson RJ, De Morais SM, Benhamou S, Bouchardy C, Blaisdell J, Ibeanu G, Wilkinson GR, Sarich TC, Wright JM, Dayer P, Goldstein JA. A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. J Pharmacol Exp Ther. 1998 Jan;284(1):356-61.

  PMID: 9435198 BACKGROUND

• Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, Ingelman-Sundberg M. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 2006 Jan;79(1):103-13. doi: 10.1016/j.clpt.2005.10.002.

  PMID: 16413245 BACKGROUND

Results Point of Contact

• Title: Zeruesenay Desta
• Organization: Indiana University School of Medicine

zdesta@iu.edu

+1 (317) 274-2823

Study Officials

• Zeruesenay Desta, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: April 29, 2008
• Study Start: March 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: January 1, 2009
• Last Updated: December 17, 2014
• Results First Posted: December 17, 2014

Record last verified: 2014-12

Locations

US (1)