PAN01: PK Study With Pantoprazole in Obese Children and Adolescents

• Sponsor: Phillip Brian Smith (Other)
• Overall Status: Completed
• CT.gov ID: NCT02186652
• Collaborator: The Emmes Company, LLC (Industry)
• Enrollment: 41
• Locations: 4
• Arm: 1
• Actual Duration (Months): 15.3
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Multicenter, comparative single-dose pharmacokinetic (PK) study

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux Disease	Drug: Pantoprazole	Phase 1

Detailed Description

Evaluate the pharmacokinetics of pantoprazole in obese children and adolescents with gastroesophageal reflux disease (GERD) following administration of an oral dose of pantoprazole.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Effect of Obesity on the Pharmacokinetics of Pantoprazole in Children and Adolescents
• Actual Study Start Date: Jun 4, 2014
• Actual Primary Completion Date: Sep 13, 2015
• Actual Study Completion Date: Sep 13, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: Pantoprazole	Drug: Pantoprazole

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax). [pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours]

   The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Cmax.

2. Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax). [pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours]

   The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Tmax.

3. PK Sampling [Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing]

   Total number of fresh plasma samples (all participants)

4. Drug Concentration in Plasma Samples [Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing]

   Concentration of panto in plasma and concentration of panto sulfone in plasma

5. Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC). [pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours]

   The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC TBW.

6. Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC). [pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours]

   The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC LBW.

7. Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F). [pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours]

   The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report CL/F TBW.

8. Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F). [pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours]

   The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F TBW.

9. Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F). [pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours]

   The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F LBW.

Secondary Outcome Measures

1. The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype [0, 1, 2, 3, 4, 6, 8, 12 hours post-dose]

   To examine the association of CYP2C19 genotype and its association with CYP2C19 phenotypes. To characterize the ability of the CYP2C19 genotype to predict pantoprazole plasma clearance, a correlation with CYP2C19 phenotype was explored using both standard linear and nonlinear regression techniques and their respective tests for significance and goodness of fit. In addition, the impact of all covariates on pantoprazole systemic exposure and apparent plasma clearance (e.g., demographic determinants of extent of obesity such as the waist:hip ratio, CYP2C19 genotype, BMI, and REE) was explored using validated population-based PK methods (NONMEM).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participant is between 6 and 17 (inclusive) years of age at the time of consent

2. BMI ≥95th percentile

3. Diagnosis of GERD established prior to 7 days before receipt of study drug dose defined as 1 or more of the following:

4. clinical symptoms consistent with GERD as determined by the investigator

5. a diagnosis of erosive esophagitis by endoscopy

6. esophageal biopsy with histopathology consistent with reflux esophagitis

7. abnormal pH-metry consistent with reflux esophagitis

8. other test result consistent with GERD

9. Written informed consent from the parent or legally authorized representative/guardian and participant assent per local IRB recommendation of age-appropriate consent and assent requirements

Exclusion Criteria:

1. Use of pantoprazole, lansoprazole, omeprazole, esomeprazole or rabeprazole within 48 hours prior to dose of study drug

2. Use of fluoxetine, fluvoxamine, ketoconazole, ticlopidine, felbamate, topiramate, valproic acid, phenobarbital, carbamazepine, erythromycin, clarithromycin, grapefruit juice, verapamil, diltiazem, cimetidine, St. John's Wort, rifampin, rifapentine within seven days prior to dose of study drug

3. Consumption of food after midnight on the day of the baseline visit

4. Symptomatic asthma

5. Type I diabetes

6. History of adverse reaction to PPI

7. Impaired hepatic activity as defined as any of the following: AST ≥150 IU/L, ALT ≥150 IU/L, total bilirubin ≥2.0 mg/dl, or alkaline phosphatase ≥600 IU/L

8. Serum creatinine ≥2.0 mg/dL

9. For females of childbearing potential, a positive pregnancy test result

10. Known infection with hepatitis B, C, or HIV

11. Any other condition that, in the opinion of the principal investigator, makes participation unadvised or unsafe.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas	Little Rock	Arkansas	United States	72202
2	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
3	East Carolina University	Greenville	North Carolina	United States	27834
4	University of Utah	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

• Phillip Brian Smith
• The Emmes Company, LLC

Investigators

• Principal Investigator: Phillip B Smith, MD, Duke Clinical Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures

Publications

None provided.

• Responsible Party: Phillip Brian Smith, Principal Investigator, Duke University
• ClinicalTrials.gov Identifier: NCT02186652
• Other Study ID Numbers: Pro00048765
• First Posted: Jul 10, 2014
• Last Update Posted: Sep 17, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Phillip Brian Smith, Principal Investigator, Duke University: obese; children; adolescents; GERD; pharmacokinetic
• Additional relevant MeSH terms: Gastroesophageal Reflux; Pantoprazole

Study Results

Participant Flow

Recruitment Details	The first participant for this study began on 8-July-2014. The last participant to complete the study was on 13-September-2015.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Period Title: Overall Study
STARTED	19	22
COMPLETED	17	22
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old	Total
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	Total of all reporting groups
Overall Participants	19	22	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10 (2)	15 (2)	12 (3)
Sex: Female, Male (Count of Participants)
Female	12 63.2%	11 50%	23 56.1%
Male	7 36.8%	11 50%	18 43.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5.3%	3 13.6%	4 9.8%
Not Hispanic or Latino	16 84.2%	19 86.4%	35 85.4%
Unknown or Not Reported	2 10.5%	0 0%	2 4.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 5.3%	0 0%	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 36.8%	6 27.3%	13 31.7%
White	8 42.1%	12 54.5%	20 48.8%
More than one race	2 10.5%	1 4.5%	3 7.3%
Unknown or Not Reported	1 5.3%	3 13.6%	4 9.8%
Region of Enrollment (participants) [Number]
United States	19 100%	22 100%	41 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	60.5 (23.7)	97.9 (19.6)	80.6 (28.5)
Weight Percentile (percentile) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentile]	96.8 (3.6)	97.9 (3.4)	97.4 (3.5)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	144.4 (13.9)	166.6 (7.4)	156.3 (15.6)
Height Percentile (percentile) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentile]	65.3 (28.9)	60.9 (29.7)	62.9 (29.1)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.0 (5.8)	35.0 (5.0)	31.7 (6.4)
BMI Percentile (percentile) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentile]	98 (1)	98 (1)	98 (1)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax).
Description	The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Cmax.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Outcome Measure Data

Analysis Population Description

All participants with evaluable data.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	same as the participant flow wording.	same as participant flow wording.
Measure Participants	18	21
Mean (Standard Deviation) [mcg/ml]	4.27 (1.43)	4.1 (1.18)

2. Primary Outcome

Title	Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax).
Description	The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Tmax.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Outcome Measure Data

Analysis Population Description

All participants with evaluable data.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Measure Participants	18	21
Median (Full Range) [hours]	2.3	2.5

3. Primary Outcome

Title	PK Sampling
Description	Total number of fresh plasma samples (all participants)
Time Frame	Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing

Outcome Measure Data

Analysis Population Description

All participants with evaluable data

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Measure Participants	19	22
Measure Plasma samples	203	235
Mean (Standard Deviation) [Plasma samples]	11 (2)	11 (2)

4. Primary Outcome

Title	Drug Concentration in Plasma Samples
Description	Concentration of panto in plasma and concentration of panto sulfone in plasma
Time Frame	Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing

Outcome Measure Data

Analysis Population Description

All participants with evaluable data

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	Edit to include: dosing and any info about the participants experience and how they were treated.	same as other arm description
Measure Participants	19	22
Measure plasma samples	203	235
Pantoprazole	1558 (1584.6)	1626.1 (1545.2)
Pantoprazole Sulfone	94.7 (49.1)	88.7 (36.8)

5. Primary Outcome

Title	Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).
Description	The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC TBW.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Outcome Measure Data

Analysis Population Description

All participants with evaluable data.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Measure Participants	18	21
Mean (Standard Deviation) [mcg*h/mL]	8.87 (4.00)	11.56 (4.81)

6. Primary Outcome

Title	Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).
Description	The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC LBW.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Outcome Measure Data

Analysis Population Description

All participants with evaluable data.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Measure Participants	18	21
Mean (Standard Deviation) [mcg*h/mL]	5.73 (2.48)	6.82 (2.70)

7. Primary Outcome

Title	Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F).
Description	The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report CL/F TBW.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Outcome Measure Data

Analysis Population Description

All participants with evaluable data.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Measure Participants	18	21
Mean (Standard Deviation) [l/h/kg TBW]	0.14 (0.07)	0.10 (0.04)

8. Primary Outcome

Title	Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).
Description	The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F TBW.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Outcome Measure Data

Analysis Population Description

All participants with evaluable data.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Measure Participants	18	21
Mean (Standard Deviation) [L/kg TBW]	0.16 (0.05)	0.14 (0.04)

9. Primary Outcome

Title	Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).
Description	The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F LBW.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours

Outcome Measure Data

Analysis Population Description

All participants with evaluable data.

Arm/Group Title	Pantoprazole 6-11 Year Old	Pantoprazole 12-17 Year Old
Arm/Group Description	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.	The study design included a screening visit (0-31days prior to baseline), during which informed consent was obtained and blood was collected for isolation of DNA for genotyping. During the Baseline Visit (Day 1) included REE measurement (before drug administration using a MedGem indirect calorimeter), study drug administration, and PK evaluation. The MedGem measures oxygen consumption (VO2) to determine resting metabolic rate. Study drug was then administered orally, and repeated blood samples of 1.0 ml each were collected at pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing. For those participants with the PM CYP2C19 genotype, an additional PK sample was to be obtained at 12 hours after dosing. Between Day 10 and Day 13 after the Baseline Visit, investigators conducted a follow-up call to assess participants' general wellness and to collect Adverse Event (AE) information.
Measure Participants	18	21
Mean (Standard Deviation) [L/kg LBW]	0.25 (0.09)	0.25 (0.07)

10. Secondary Outcome

Title	The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype
Description	To examine the association of CYP2C19 genotype and its association with CYP2C19 phenotypes. To characterize the ability of the CYP2C19 genotype to predict pantoprazole plasma clearance, a correlation with CYP2C19 phenotype was explored using both standard linear and nonlinear regression techniques and their respective tests for significance and goodness of fit. In addition, the impact of all covariates on pantoprazole systemic exposure and apparent plasma clearance (e.g., demographic determinants of extent of obesity such as the waist:hip ratio, CYP2C19 genotype, BMI, and REE) was explored using validated population-based PK methods (NONMEM).
Time Frame	0, 1, 2, 3, 4, 6, 8, 12 hours post-dose

Outcome Measure Data

Analysis Population Description

Total analyzed #participants is 38. Total #participants in age groups is 37 excluding one poor-metabolizer. Poor metabolizer is defined as a participant who had *2/*2 alleles; intermediate metabolizer is defined as a participant who had *1/*2 or *2/*17 alleles; extensive metabolizer is defined as a participant who had *1/*1 or *1/*17 alleles.

Arm/Group Title	*2*2 Allele	*1/*2 Allele	*1/*1 Allele or *1/*17 Allele
Arm/Group Description	Poor metabolizer	Intermediate Metabolizer	Extensive Metabolizer
Measure Participants	1	16	21
Median (Full Range) [L/h]	1.29	6.00	8.97

Adverse Events

Time Frame	Adverse events were followed up to 10 days post study dose.
Adverse Event Reporting Description	An AE is any untoward medical occurrence in humans, whether or not considered drug-related, which occurs during the conduct of a clinical trial. (Any change in clinical status, ECGs, routine labs, x-rays, physical examinations, etc., that is considered clinically significant by the study investigator is considered an AE.)
Arm/Group Title	6-11 Year Old Adverse Events		12-17 Year Old Adverse Events
Arm/Group Description	Study participants were selected from obese children and adolescents ranging in age from 6 17 years (inclusive) and seen in the outpatient clinic for the diagnosis or treatment of GERD. The target enrollment was 40 participants (20 participants 6-11 years of age and up to 20 participants 12 17 years of age). Potential study participants could come from any outpatient clinical setting within participating institutions where children with GERD were seen for evaluation and/or treatment.		Study participants were selected from obese children and adolescents ranging in age from 6 17 years (inclusive) and seen in the outpatient clinic for the diagnosis or treatment of GERD. The target enrollment was 40 participants (20 participants 6-11 years of age and up to 20 participants 12 17 years of age). Potential study participants could come from any outpatient clinical setting within participating institutions where children with GERD were seen for evaluation and/or treatment.
All Cause Mortality
	6-11 Year Old Adverse Events		12-17 Year Old Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/22 (0%)
Serious Adverse Events
	6-11 Year Old Adverse Events		12-17 Year Old Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	6-11 Year Old Adverse Events		12-17 Year Old Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		6/22 (27.3%)
Gastrointestinal disorders
Vomiting	0/19 (0%)	0	1/22 (4.5%)	1
General disorders
Pyrexia	0/19 (0%)	0	1/22 (4.5%)	1
Infections and infestations
Urinary Tract Infection	0/19 (0%)	0	1/22 (4.5%)	1
Injury, poisoning and procedural complications
Laceration	0/19 (0%)	0	1/22 (4.5%)	1
Nervous system disorders
Headache	1/19 (5.3%)	1	1/22 (4.5%)	1
Renal and urinary disorders
nephrolithiasis	0/19 (0%)	0	1/22 (4.5%)	1
Reproductive system and breast disorders
Dysmenorrhoea	0/19 (0%)	0	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Hiccups	0/19 (0%)	0	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.