E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastroesophageal Reflux Disease (GERD) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017924 |
E.1.2 | Term | Gastroesophageal reflux |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the PK of pantoprazole, following single and multiple IV doses of pantoprazole sodium in pediatric subjects aged 1 to less than 2 years old.
To characterize the PK of pantoprazole, following single and multiple IV doses of pantoprazole sodium in pediatric subjects aged 2 to 16 years old. |
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E.2.2 | Secondary objectives of the trial |
To determine the safety, tolerability and PK of single and multiple IV doses of pantoprazole sodium in each of the two independent age cohorts.
To assess the CYP2C19 genotype in pediatric subjects receiving IV pantoprazole sodium, to determine the presence of the gene for the major enzyme responsible for metabolism of pantoprazole. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document indicating that the parent/legal guardian has been informed of all pertinent aspects of the study.
2. Evidence of a personally signed and dated assent, indicating that the subject understands the nature of all pertinent aspects of the study, and is willing to participate in the study activities, if applicable, as consistent with the subject’s age and ability to provide assent.
3. The subject (to degree appropriate for age) and parent or legal guardian are able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and are likely to complete the study as planned.
4. Subjects aged 1 to 16 years who in the judgment of the investigator are candidates for gastric acid suppression therapy (ie, those with a presumptive diagnosis of GERD, a clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD) and whom the investigator judges would need to receive IV PPI therapy for at least 4 days.
5. Physical examination and clinical laboratory evaluations within normal limits unless the investigator documents that the deviations are not clinically significant or are directly related to the reason for gastric acid suppression therapy or to the subject’s underlying disease process.
6. Body weight >5th percentile for subject’s age.
7. Y-site or dedicated IV line for administration of pantoprazole sodium.
8. Expected survival for at least 30 days.
9. The subject (to degree appropriate for age) and parent or legal guardian are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
10. Fertile male subjects and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment.
a. If subject is a female of childbearing potential, she must agree to use adequate contraception and must have a negative serum pregnancy test within 24 hours prior to administration of investigational product.
Female subjects of non-childbearing potential must meet at least one of the following criteria:
a. Premenarchal: The investigator (or other appropriate staff) must discuss the subject's premenarchal status with the subject or parent/caregiver at office visits and during telephone contacts, as subjects who achieve menarche during the study would no longer be considered "female subjects of nonchildbearing potential" and must comply with the protocol requirements applicable to women of childbearing potential;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure; or
d. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level confirming the post-menopausal state.
All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential.
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E.4 | Principal exclusion criteria |
1. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Participation in other studies involving investigational drug(s) within 30 days or 5 half-lives prior to study entry and/or during study participation.
3. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
4. Pregnant females; breastfeeding females; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after last dose of investigational product.
5. Serum creatine kinase levels >3x upper limit of normal.
6. Known history of human immunodeficiency virus (HIV) or clinical manifestations of acquired immune deficiency syndrome (AIDS).
7. Known hypersensitivity to proton pump inhibitors (PPIs), including pantoprazole sodium or to any substituted benzimidazole or to any of the excipients.
8. History of treatment with any PPI (eg, omeprazole, esomeprazole, lansoprazole, rabeprazole, or pantoprazole sodium) within 2 days (i.e. 48 hours) before investigational product dosing on Day 1.
9. Use of Histamine 2 Receptor Blockers (H2RAs) (eg, cimetidine, famotidine, ranitidine or nizatidine), sucralfate, misoprostol, or prokinetic agents (eg, cisapride, urecholine, erythromycin or metoclopramide), and bismuth preparations within 1 day (i.e. 24 hours) before investigational product dosing on Day 1, whether prescription or over the counter.
10. Any disorder requiring chronic (every day) use of warfarin, carbamazepine, or phenytoin, methotrexate, atazanavir or nelfinavir, clopidogrel, and potent inhibitors and inducers of CYP2C19.
11. Chronic (daily) use of glucocorticoids (eg, prednisone, prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
12. Active malignancy of any type, or history of a malignancy (Subject with a history of malignancies that have been surgically removed or eradicated by irradiation or chemotherapy and who have no evidence of recurrence for at least 5 years before Screening are acceptable).
13. Alanine aminotransferase (ALT) or Blood urea nitrogen (BUN) >2.0 Upper limit of normal (ULN) or estimated creatinine >1.5 X ULN for age or any other laboratory abnormality considered by the Investigator to be clinically significant within 14 days before Screening.
14. In the Investigator's opinion, a chronic condition (eg, diabetes, epilepsy), which is either not stable or well controlled and may interfere with the conduct of the study.
15.History of sensitivity to heparin or heparin-induced thrombocytopenia.
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E.5 End points |
E.5.1 | Primary end point(s) |
PK Parameters: clearance (CL) and volume of distribution (Vd).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
PK Parameters to be estimated from the population PK model: Maximum plasma concetration (Cmax), area under the plasma concetration-time profile from time zero to the 24 hour time post dose (AUC24), area under the plasma concetration-time profile from time zero extrapolated to infinite time (AUCinf) and terminal phase half-life (T1/2) of pantoprazole following single and multiple IV doses.
1. Safety and tolerability of single- and multiple doses of IV pantoprazole sodium for each of the two age cohorts will be assessed by physical examinations, adverse event (AE) monitoring, clinical laboratory measurements, blood pressure, and pulse rate.
2. CYP2C19 genotype to determine the presence of the gene for the major enzyme responsible for metabolism of pantoprazole. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Throughout the trial.
2. Samples for CYP2C19 genotype analysis will be collected pre-dose. |
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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 | Yes |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
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) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Mexico |
Serbia |
European Union |
Argentina |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |