E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
12- to 17-year-olds inclusive with GERD or symptoms of GERD. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017885 |
E.1.2 | Term | Gastrooesophageal reflux disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective:
To determine AUC after single and repeated (multiple) oral doses of 20 mg and 40 mg esomeprazole magnesium in 12- to 17-year-olds inclusive with GERD or symptoms of GERD.
|
|
E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
To determine the AUC(0-t), Cmax, tmax, t½z, apparent oral clearance (CL/F), apparent volume of distribution during terminal phase (Vz /F), and apparent volume of distribution at steady state (Vss/F) after single and repeated (multiple) oral doses of 20 mg and 40 mg esomeprazole magnesium in 12- to 17-year-olds inclusive with GERD or symptoms of GERD.
To assess the safety and tolerability of esomeprazole magnesium in 12- to 17-year-olds with GERD or symptoms of GERD.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the study, all of the following criteria needed to be fulfilled:
1. Provision of signed written informed consent from subject’s parent/guardian with assent from the subject.
2. Subjects, both male and female, between the ages of 12 and 17 inclusive.
3. Subjects must have had a clinical diagnosis of GERD made by the investigator based on any of the following factors: history, physical examination, symptoms identified during review of systems, laboratory test results, or information from diagnostic testing. Notes in the subject’s medical record and/or other source documentation were used to support the diagnosis.
4. Females must have had a negative pregnancy test at screening and prior to dosing on Day 1 and Day 8.
5. Females of childbearing potential must have used a reliable form of contraception, other than systemic, hormonal contraceptives, if sexually active.
6. Subjects were able to swallow capsules.
7. Subjects were able to tolerate discontinuation of their PPI therapy for 7 days and/or H2RA therapy for 3 days prior to the first dose of study drug and during the study.
8. Subjects were willing to communicate with the investigator and comply with all study procedures.
|
|
E.4 | Principal exclusion criteria |
Any of the following was regarded as a criterion for exclusion from the study:
1. Subjects who had received an experimental compound or participated in another clinical trial within 28 days preceding the screening visit.
2. Female subjects who were pregnant, wished to become pregnant during the study or were lactating.
3. Female subjects who were taking a systemic, hormonal contraceptive (eg, oral, parenteral, or transdermal).
4. Subjects who had a history or presence of GI, hepatic, or renal disease or other condition that could have interfered with absorption, distribution, metabolism or excretion of esomeprazole.
5. Subjects who had a seizure disorder or unstable diabetes mellitus.
6. Subjects who had any acute or chronic illness or a medical history, which, in the opinion of the investigator, could have compromised the subject’s safety or successful participation in the study.
7. Subjects who had a history of multiple drug allergies unless otherwise agreed by AstraZeneca and the investigator.
8. Hypersensitivity, allergy or intolerance to esomeprazole, any ingredient in its formulation or any drug with a similar chemical structure to esomeprazole.
9. Subjects who were currently taking anti-epileptic medications, phenytoin, mephenytoin, antineoplastic agents, pro-motility drugs (prokinetics), sucralfate or Warfarin.
10. Subjects who had taken any drug known to affect the PK of esomeprazole within 14 days prior to screening. These drugs included, but were not limited to, enzyme inducers such as phenobarbital, carbamazepine, rifampicin and St. John’s Wort, or enzyme inhibitors such as clarithromycin, erythromycin, SSRIs, cimetidine, itraconazole, protease inhibitors and ketaconazole.
11. Subjects who had a history of drug abuse or alcohol dependence or current abuse.
12. Subjects who were unwilling to take the study drug according to dosing instructions.
13. Subjects who had clinically significant abnormal values at screening from laboratory measurements, physical examination or vital signs which, in the opinion of the investigator, may have either put the subject at risk when participating in the study, or affected the subject’s ability to participate in the study, other than those directly related to some concurrent and stable disease or if the values from laboratory measurements were both unexplained and potentially significant.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Variables
- Pharmacokinetic
Blood samples were analyzed to determine the PK (AUC, AUC(0-t), Cmax, tmax, t½z, CL/F, Vz /F, and Vss /F) of esomeprazole magnesium in the specified population. The AUC was the primary variable.
- Safety
Safety and tolerability were assessed by means of incidence and severity of adverse events (AEs), vital signs, laboratory parameters and physical examinations.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK measurements on dosing day 1 and final dosing day 8. Safety up to 2 weeks post last dosing. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 2 |