Clinical trial NCT02186652: PK Study With Pantoprazole in Obese Children and Adolescents
Official title: The Effect of Obesity on the Pharmacokinetics of Pantoprazole in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastroesophageal Reflux Disease
Keywords: obese
children
adolescents
GERD
pharmacokinetic
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: The Emmes Company, LLC
First posted: 2014-07-10
Enrollment: 41
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Multicenter, comparative single-dose pharmacokinetic (PK) study

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.

Eligibility criteria: 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:

   1. clinical symptoms consistent with GERD as determined by the investigator
   2. a diagnosis of erosive esophagitis by endoscopy
   3. esophageal biopsy with histopathology consistent with reflux esophagitis
   4. abnormal pH-metry consistent with reflux esophagitis
   5. other test result consistent with GERD
4. 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.

Primary outcomes:
measure: Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax).
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
measure: Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax).
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
measure: PK Sampling
timeFrame: 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
measure: Drug Concentration in Plasma Samples
timeFrame: 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
measure: Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
measure: Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
measure: Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F).
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
measure: Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
measure: Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Secondary outcomes:
measure: The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12 hours post-dose
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Duke Clinical Research Institute
name: Phillip B Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shakhnovich V, Smith PB, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL; Best Pharmaceuticals for Children Act - Pediatric Trials Network. Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures. J Pediatr. 2018 Feb;193:102-108.e1. doi: 10.1016/j.jpeds.2017.10.011.