Trial Outcomes & Findings for Pharmacokinetics of Pantoprazole and CYP2C19 Activity in Children and Adolescents With GERD: A Pilot Study (NCT NCT01887743)

NCT ID: NCT01887743

Last Updated: 2021-12-03

Results Overview

Pantoprazole apparent oral drug clearance (CL/F) adjusted for weight for children with the most common CYP2C19 genotypes (i.e., \*1/1, \*1/17, \*1/2, \*2/17). Only children with evaluable plasma samples (i.e., at least 85% of planned plasma samples collected) were included in this analysis (n=57).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 71 participants
• Primary outcome timeframe: 8 hours
• Results posted on: 2021-12-03

Participant Flow

Participant milestones

Measure	Obese BMI for age at or above the 95th percentile	Overweight BMI for age 85-94th percentile	Normal Weight BMI for age \<85th percentile
Overall Study STARTED	20	19	32
Overall Study COMPLETED	19	17	29
Overall Study NOT COMPLETED	1	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Pantoprazole and CYP2C19 Activity in Children and Adolescents With GERD: A Pilot Study

Baseline characteristics by cohort

Measure	Normal Weight n=29 Participants BMI10-84th percentile for age	Overweight n=17 Participants BMI 85-94th percentile for age	Obese n=19 Participants BMI at or above 95th percentile for age	Total n=65 Participants Total of all reporting groups
Age, Continuous	13.7 years STANDARD_DEVIATION 3.8 • n=5 Participants	14.9 years STANDARD_DEVIATION 2.6 • n=7 Participants	12.7 years STANDARD_DEVIATION 3.0 • n=5 Participants	13.7 years STANDARD_DEVIATION 3.3 • n=4 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	13 Participants n=7 Participants	13 Participants n=5 Participants	40 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	17 Participants n=7 Participants	15 Participants n=5 Participants	59 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	29 participants n=5 Participants	17 participants n=7 Participants	17 participants n=5 Participants	63 participants n=4 Participants
BMI percentile for age	62.0 percentile for age STANDARD_DEVIATION 18.2 • n=5 Participants	89.3 percentile for age STANDARD_DEVIATION 2.5 • n=7 Participants	97.7 percentile for age STANDARD_DEVIATION 1.8 • n=5 Participants	79.0 percentile for age STANDARD_DEVIATION 19.9 • n=4 Participants

PRIMARY outcome

Timeframe: 8 hours

Population: Only children with evaluable plasma samples (i.e., at least 85% of planned plasma samples collected) were included in this analysis (n=57).

Pantoprazole apparent oral drug clearance (CL/F) adjusted for weight for children with the most common CYP2C19 genotypes (i.e., *1/1, *1/17, *1/2, *2/17). Only children with evaluable plasma samples (i.e., at least 85% of planned plasma samples collected) were included in this analysis (n=57).

Outcome measures

Measure	Normal Weight n=28 Participants BMI10-84th percentile for age	Overweight n=16 Participants BMI 85-94th percentile for age	Obese n=13 Participants BMI at or above 95th percentile for age
Pantoprazole Apparent Oral Clearance	0.42 L/hr/kg Standard Deviation 0.27	0.29 L/hr/kg Standard Deviation 0.12	0.23 L/hr/kg Standard Deviation 0.13

PRIMARY outcome

Timeframe: 8 hours

Population: Only children with evaluable plasma samples (i.e., at least 85% of planned plasma samples collected) were included in this analysis (n=57).

Pantoprazole apparent oral drug clearance (CL/F), not adjusted for weight, for children with the most common CYP2C19 genotypes (i.e., *1/1, *1/17, *1/2, *2/17). Only children with evaluable plasma samples (i.e., at least 85% of planned plasma samples collected) were included in this analysis (n=57).

Outcome measures

Measure	Normal Weight n=28 Participants BMI10-84th percentile for age	Overweight n=16 Participants BMI 85-94th percentile for age	Obese n=13 Participants BMI at or above 95th percentile for age
Unadjusted Pantoprazole Apparent Oral Clearance	20.4 L/hr Standard Deviation 14.2	18.7 L/hr Standard Deviation 7.43	16.8 L/hr Standard Deviation 8.55

SECONDARY outcome

Timeframe: 3 hours

Population: The mean precision was calculated at 5 timepoints during the first 3 hours post-drug administration to test the breath test's ability to discriminate CYP2C19 EM from IM. All EM/IM children with evaluable breath test data were included as a single study group in this analysis.

Children with common CYP2C19 genotypes (*1/*1, *1*17, *1/*2, *2/*17) who had evaluable breath test data (n=59) were included to evaluate the breath test's precision in discriminating the CYP2C19 Extensive Metabolizer (EM; *1/*1, *1*17) from the Intermediate Metabolizer (IM; *1/*2, *2/*17) phenotype in the first 3 hrs after study drug administration. A 3-hour window was chosen for convenience. A predictive model using breath test features (change in ratio of C12-to-C13 in exhaled CO2) was build and validated to predictphenotype for each child. We drew bootstrap samples, each stratified to preserve the observed prevalence of EM/IMs in the original cohort (n=59). Sampling with replacement left out 38% of the original sample to use as a test dataset to validate model performance. For each bootstrap sample, a 500-tree Extremely randomized Extra-Tree Forest was constructed after seeding. Using phenotypes predicted by the forest, predictive accuracy was assessed by computing precision.

Outcome measures

Measure	Normal Weight n=59 Participants BMI10-84th percentile for age	Overweight BMI 85-94th percentile for age	Obese BMI at or above 95th percentile for age
Precision of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 30 minutes	77.3 percent true EM in total EM predicted Standard Deviation 5.5	—	—
Precision of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 60 minutes	77.7 percent true EM in total EM predicted Standard Deviation 5.0	—	—
Precision of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 90 minutes	77.3 percent true EM in total EM predicted Standard Deviation 5.0	—	—
Precision of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 120 minutes	77.8 percent true EM in total EM predicted Standard Deviation 5.1	—	—
Precision of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 180 minutes	76.9 percent true EM in total EM predicted Standard Deviation 5.0	—	—

SECONDARY outcome

Timeframe: 3 hours

Population: The mean recall was calculated at 5 timepoints during the first 3 hours post-drug administration to test the breath test's ability to discriminate CYP2C19 EM from IM. All EM/IM children with evaluable breath test data were included as a single study group in this analysis.

Children with common CYP2C19 genotypes (*1/*1, *1*17, *1/*2, *2/*17) who had evaluable breath test data (n=59) were included to evaluate the breath test's precision in discriminating the CYP2C19 Extensive Metabolizer (EM; *1/*1, *1*17) from the Intermediate Metabolizer (IM; *1/*2, *2/*17) phenotype in the first 3 hrs after study drug administration. A 3-hour window was chosen for convenience. A predictive model using breath test features (change in ratio of C12-to-C13 in exhaled CO2) was build and validated to predictphenotype for each child. We drew bootstrap samples, each stratified to preserve the observed prevalence of EM/IMs in the original cohort (n=59). Sampling with replacement left out 38% of the original sample to use as a test dataset to validate model performance. For each bootstrap sample, a 500-tree Extremely randomized Extra-Tree Forest was constructed after seeding. Using phenotypes predicted by the forest, predictive accuracy was assessed by computing recall.

Outcome measures

Measure	Normal Weight n=59 Participants BMI10-84th percentile for age	Overweight BMI 85-94th percentile for age	Obese BMI at or above 95th percentile for age
Recall of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 30 minutes	87.8 percent identified EM out of total EM Standard Deviation 9.5	—	—
Recall of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 60 minutes	93.6 percent identified EM out of total EM Standard Deviation 7.9	—	—
Recall of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 90 minutes	92.3 percent identified EM out of total EM Standard Deviation 7.9	—	—
Recall of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 120 minutes	92.4 percent identified EM out of total EM Standard Deviation 7.5	—	—
Recall of Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 180 minutes	90.2 percent identified EM out of total EM Standard Deviation 8.1	—	—

SECONDARY outcome

Timeframe: 3 hours

Population: The mean F1 was calculated at 5 timepoints during the first 3 hours post-drug administration to test the breath test's ability to discriminate CYP2C19 EM from IM. All EM/IM children with evaluable breath test data were included as a single study group in this analysis.

Children with common CYP2C19 genotypes (*1/*1, *1*17, *1/*2, *2/*17) who had evaluable breath test data (n=59) were included to evaluate the breath test's precision in discriminating the CYP2C19 Extensive Metabolizer (EM; *1/*1, *1*17) from the Intermediate Metabolizer (IM; *1/*2, *2/*17) phenotype in the first 3 hrs after study drug administration. A 3-hour window was chosen for convenience. A predictive model using breath test features (change in ratio of C12-to-C13 in exhaled CO2) was build and validated to predictphenotype for each child. We drew bootstrap samples, each stratified to preserve the observed prevalence of EM/IMs in the original cohort (n=59). Sampling with replacement left out 38% of the original sample to use as a test dataset to validate model performance. For each bootstrap sample, a 500-tree Extremely randomized Extra-Tree Forest was constructed after seeding. Using phenotypes predicted by the forest, predictive accuracy was assessed by computing the F1.

Outcome measures

Measure	Normal Weight n=59 Participants BMI10-84th percentile for age	Overweight BMI 85-94th percentile for age	Obese BMI at or above 95th percentile for age
Harmonic Mean of Precision and Recall (F1) of the Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 30 minutes	81.9 percent mean predictive performance Standard Deviation 5.5	—	—
Harmonic Mean of Precision and Recall (F1) of the Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 60 minutes	84.7 percent mean predictive performance Standard Deviation 4.7	—	—
Harmonic Mean of Precision and Recall (F1) of the Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 90 minutes	83.8 percent mean predictive performance Standard Deviation 4.6	—	—
Harmonic Mean of Precision and Recall (F1) of the Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 120 minutes	84.3 percent mean predictive performance Standard Deviation 4.5	—	—
Harmonic Mean of Precision and Recall (F1) of the Breath Test to Discriminate the CYP2C19 Extensive Metabolizer (EM) From Intermediate Metabolizer (IM) Phenotype 180 minutes	82.8 percent mean predictive performance Standard Deviation 4.7	—	—

Adverse Events

Normal Weight

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Overweight

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Obese

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

Valentina Shakhnovich, MD

Children's Mercy Kansas City

Phone: 816-302-3068

Email: vshakhnovich@cmh.edu

Results disclosure agreements

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