| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acid-Related Disorders in Infants aged 1 to 11 months |
|
| E.1.1.1 | Medical condition in easily understood language |
| Acid-Related Disorders in Infants |
|
| 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 | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10066874 |
| E.1.2 | Term | Gastroesophageal reflux disease |
| E.1.2 | System Organ Class | 100000004856 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10000479 |
| E.1.2 | Term | Acid reflux (oesophageal) |
| E.1.2 | System Organ Class | 100000004856 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10019326 |
| E.1.2 | Term | Heartburn |
| E.1.2 | System Organ Class | 100000004856 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063657 |
| E.1.2 | Term | Erosive esophagitis |
| E.1.2 | System Organ Class | 100000004856 |
|
| 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 assess the PK of dexlansoprazole after daily administration for 7 days in pediatric subjects aged 1 to 11 months, inclusive, with acid-related diseases.
To assess the safety of dexlansoprazole in pediatric subjects aged 1 to 11 months, inclusive, after daily administration for 8 weeks.
To assess the PD of dexlansoprazole after daily administration for 7 days in pediatric subjects aged 1 to 11 months, inclusive, with acid-related diseases. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria:
1. Prior to any study-specific procedures being performed and after having the study fully explained and all questions answered, the informed consent form (ICF) must be signed and dated by parent(s) or legal guardian(s). Screening Period starts at the time of consent.
2. Subject is a male or female infant 1 to 11 months old, inclusive, on Day 1. Infants who were born prematurely must be ≥45 weeks old based on corrected gestational age.
3. At the Initial Screening and Day -1 visits, subject must have body weight percentile-for-age within the 5th through 95th percentile by age, inclusive, as determined by the WHO growth chart.
4. Subjects must be ≥3.4 kg at the Screening and Day -1 visits.
5. Subjects who take prescription or nonprescription PPIs, histamine-2 receptor antagonists (H2RAs), sucralfate, or antacids on a regular or as required basis must agree to discontinue use on Day -1 (except cimetidine, which must be discontinued 28 days prior to Day -1), and agree to discontinue use throughout the study.
6. Subject must have endoscopically proven EE, a history of EE, and/or the subject has 1 or more of the following underlying conditions that predispose the subject to chronic GERD and EE: moderate to severe neurologic impairment, repaired esophageal atresia, hiatal hernia, cystic fibrosis, bronchopulmonary dysplasia, or end-stage renal disease.
7. Except for subjects with EE, history of EE, or repaired esophageal atresia, subjects have:
- Received prior PPI therapy for a minimum of 2 weeks during any time in the past with symptomatic response and have demonstrated a recurrence of symptoms following at least 1 attempted withdrawal of PPI therapy
AND
- Have undergone esophageal pH monitoring in the recent past to document that their symptoms are due to acid-mediated disease.
8. Subject must be able to ingest study medication granules sprinkled on 1 tablespoon of applesauce or pureed apples, or as a mixture of granules in water administered via oral syringe.
9. Subject must be at least 7 days postsurgery by dosing on Day 1 and have no anticipated need for surgery during the study.
10. Screening laboratory samples must be collected between Day -7 and Day -2 and the results must be within the range expected for this infant population (except gastrin and hepatitis panel results as those results will be available after Day 1). The laboratory results should indicate no CS abnormality in chemistry (including electrolytes, blood urea nitrogen [BUN]), creatinine, glucose, ALT, AST, and total bilirubin), hematology (complete blood cell count, including differential), and urinalysis parameters (if standard of care). |
|
| E.4 | Principal exclusion criteria |
A subject who meets any of the following criteria will not qualify for entry into the study:
1. Subject has evidence of cardiovascular, pulmonary, central nervous system, hepatic, hematopoietic, renal, metabolic, endocrine or gastrointestinal disease, or serious allergy, asthma, or allergic skin rash that suggests CS, uncontrolled underlying disease or condition (other than the disease being studied and/or identified as the main criterion for inclusion), that may impact the ability of the subject to participate or potentially may confound the study results.
2. Subject has known history of or current presence of peptic ulcers or gastrointestinal bleeding (hematemesis, hematochezia).
3. Subject has poor venous access or any contraindication to blood sampling.
4. Subject has known history of eosinophilic gastroenteropathy, or a coexisting disease affecting the esophagus, including esophageal varices, viral or fungal infection, or esophageal stricture, history of radiation therapy or cryotherapy to the esophagus, and caustic or physiochemical trauma such as sclerotherapy to the esophagus.
5. Subject has active malabsorption syndrome, cow’s milk intolerance, milk protein allergy, or celiac disease.
6. Subject has any finding in his/her medical history, physical examination, or safety clinical laboratory tests giving reasonable suspicion of a disease that might interfere with the conduct of the study or that would contraindicate taking dexlansoprazole delayed-release capsules or a similar drug in the same class (ie, PPIs).
7. Subject has a known hypersensitivity to any PPI or any component of the formulation of dexlansoprazole delayed-release capsules (see most current version of the Dexilant Full Prescribing Information).
8. The subject is required to take excluded medications or it is anticipated that the subject will require treatment with at least 1 of the disallowed concomitant medications during the study evaluation period as specified in the Excluded Medications and Dietary Products.
9. Subject has a history of malignant disease.
10. Subject has a known history of infection with the human immunodeficiency virus.
11. Subject has lost >10% of the total blood volume, undergone plasmapheresis, or has had a transfusion of any blood product within 90 days prior to the first dose of study medication.
12. Subject has consumed products detailed in Section 7.3, Excluded Medications and Dietary Products during the time periods listed, or parent(s) or legal guardian(s) is unwilling to agree to subject abstaining from products listed in Section 7.3 while participating in the study.
13. Subject has participated in a study of an investigational agent (including dosing or follow-up) within 30 days prior to Screening.
14. Subject has a Screening Visit laboratory value that the principal investigator and sponsor consider to be CS.
15. The subject has: creatinine >1.5 mg/dL, ALT and/or AST >2 times the ULN, or total bilirubin >2.0 mg/dL with AST/ALT elevated above the limits of normal values.
16. The subject or parent/legal guardian is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study or may consent under duress.
17. Parent/legal guardian, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
18. Subject has any congenital anomaly of the upper gastric intestinal tract that might interfere with gastrointestinal motility, pH, or absorption, or has an active or known history of necrotizing enterocolitis that has been surgically corrected.
19. Subject has clinical evidence of acute sepsis. Infants on chronic antibiotics who are otherwise clinically stable may be enrolled in the study at the discretion of the investigator.
20. Subject has received a vaccine within 48 hours prior to dosing on Day 1.
21. Subject has used intravenous or oral antifungal agents within the 7 days prior to Day -1.
22. Subject has used mucosal protective agent (eg, sucralfate) within 6 hours prior to dosing on Day 1. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoints of this study will be the following dexlansoprazole PK parameters
derived on Confinement Day 1:
• Maximum observed plasma concentration (Cmax).
• Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUCt) and area under the plasma concentration-time curve during a dosing interval, where tau (τ) is the length of the dosing interval (AUCτ).
• Dose-normalized Cmax and area under the plasma concentration-time curves (AUCs).
• The difference in the percent of time with intragastric pH>4 during the 24-hour period on Day -1 (Baseline) and on Confinement Day 1 postdose.
• The difference in 24-hour mean intragastric pH on Day -1 (Baseline) and postdose on Confinement Day 1. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
|
| 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 | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Parallel design, multiple comparative doses of same IMP |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| 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 |
| Israel |
| Italy |
| Mexico |
| Poland |
| United States |
|
| 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.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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