Trial Outcomes & Findings for Rapid Screening Phenotype Test To Evaluate CYP 2C19 Enzyme Activity Using Stable Isotope [13C]Pantoprazole (NCT NCT00668902)

NCT ID: NCT00668902

Last Updated: 2014-12-17

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 25 participants
• Primary outcome timeframe: baseline and 2.5, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min after dosing
• Results posted on: 2014-12-17

Participant Flow

Participant milestones

Measure	EM of CYP2C19 CYP2C19 enzyme activity in extensive metabolizers of CYP2C19 (CYP2C19\*1/\*1 genotype, or wild type) was measured by 13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes	IM of CYP2C19 CYP2C19 activity in heterozygous for deficient CYP2C19 alleles (\*2 and \*3, IM of CYP2C19) was measured by (13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes	PM of CYP2C19 Homozygous for CYP2C19 null alleles (\*2/\*2, \*2/\*3 or \*3/\*3, Poor metabolizers) was measured by (13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes
Overall Study STARTED	10	10	5
Overall Study COMPLETED	10	10	5
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	EM of CYP2C19 n=10 Participants CYP2C19 enzyme activity in extensive metabolizers of CYP2C19 (CYP2C19\*1/\*1 genotype, or wild type) was measured by 13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes	IM of CYP2C19 n=10 Participants CYP2C19 activity in heterozygous for deficient CYP2C19 alleles (\*2 and \*3, IM of CYP2C19) was measured by (13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes	PM of CYP2C19 n=5 Participants Homozygous for CYP2C19 null alleles (\*2/\*2, \*2/\*3 or \*3/\*3, Poor metabolizers) was measured by (13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes	Total n=25 Participants Total of all reporting groups
Age, Continuous	26.2 years STANDARD_DEVIATION 5.3 • n=5 Participants	26.4 years STANDARD_DEVIATION 6.1 • n=7 Participants	24.3 years STANDARD_DEVIATION 3.3 • n=5 Participants	25.63 years STANDARD_DEVIATION 1.159 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	5 participants n=5 Participants	25 participants n=4 Participants
BMI	24.8 kg/m^2 STANDARD_DEVIATION 3.6 • n=5 Participants	24.8 kg/m^2 STANDARD_DEVIATION 3.5 • n=7 Participants	23 kg/m^2 STANDARD_DEVIATION 1.3 • n=5 Participants	24.2 kg/m^2 STANDARD_DEVIATION 1.039 • n=4 Participants

PRIMARY outcome

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

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).

Outcome measures

Measure	EM of CYP2C19 n=10 Participants CYP2C19 enzyme activity in extensive metabolizers of CYP2C19 (CYP2C19\*1/\*1 genotype, or wild type) was measured by 13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes	IM of CYP2C19 n=10 Participants CYP2C19 activity in heterozygous for deficient CYP2C19 alleles (\*2 and \*3, IM of CYP2C19) was measured by (13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes	PM of CYP2C19 n=5 Participants Homozygous for CYP2C19 null alleles (\*2/\*2, \*2/\*3 or \*3/\*3, Poor metabolizers) was measured by (13C)Pantoprazole breath test. \[13C\]Pantoprazole: \[13C\]Pantoprazole was administered to EM, IM and PM of CYP2C19 and enzyme activity was measured through breath test and compared among the genotypes
DOBmax (Maximum Value of DOB)	4.44 ratio Standard Deviation 1.79	3.49 ratio Standard Deviation 1.18	0.92 ratio Standard Deviation 0.18

Adverse Events

EM of CYP2C19

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

IM of CYP2C19

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PM of CYP2C19

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Zeruesenay Desta

Indiana University School of Medicine

Phone: +1 (317) 274-2823

Email: zdesta@iu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place