E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic nonerosive GERD in paediatric subjects aged 1 to 11 years |
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E.1.1.1 | Medical condition in easily understood language |
Reflux disease in children |
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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 | 19.0 |
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 |
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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 assess the safety and effectiveness of treatment with QD oral administration of dexlansoprazole delayed release capsules (15,30, and 60 mg) in pediatric subjects aged 1 to 11 years with symptomatic nonerosive GERD |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria:
1. In the opinion of the investigator, the subject (as age appropriate) and/or parent(s)/legal guardian is capable of understanding and complying with protocol requirements.
2. Prior to any study-specific procedures being performed, the informed consent and the assent form (as applicable) must be signed and dated by parent(s) or legal guardian and by the subject respectively, if appropriate.
3. The subject has a medical history of symptoms of GERD for at least 3 months prior to Screening.
4. The subject has a medical history of at least 1 failed attempted withdrawal of prior PPI/acid suppressive therapy and a return of symptoms upon withdrawal.
5. The subject has met the eDiary qualification criteria as assessed by the PGSDD, defined as hurting or burning in the stomach, chest, or throat on at least 3 of any 7 consecutive days during the Screening Period.
6. Subject has either (1) a positive endoscopy with both a HD Grade 1 and a HFRE Scale Grade <2, OR (2) an endoscopy with HD Grade 0 and a documented pH-metry suggestive of acid related disease. The pH-metry should be performed during Screening or within 6 months of signing informed consent and assent (as applicable) for GERD symptoms. An endoscopy performed within 1 week prior to signing informed consent and assent (as applicable), is an acceptable replacement for the screening endoscopy if GERD is documented by the HD classification scale criterion previously described, protocol-required biopsies were collected and endoscopic pictures were obtained.
7. Subject is male or female and age 1 to 11 years inclusive at Screening. |
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E.4 | Principal exclusion criteria |
A subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject has evidence of cardiovascular, pulmonary, central nervous system, hepatic, hematopoietic, renal, or metabolic disorder, severe allergy, asthma, or allergic skin rash that suggests any uncontrolled, clinically significant underlying disease or condition (other than the disease being studied), which may impact the ability of the subject to participate or potentially confound the study results.
2. The subject has a coexisting disease affecting the esophagus (eg, esophageal varices, scleroderma, viral or fungal infection, or esophageal stricture), history of radiation therapy orcryotherapy to the esophagus, caustic or physiochemical trauma such as sclerotherapy to the esophagus.
3. The subject has any findings in his/her medical history, physical examination, or safety clinical laboratory tests giving reasonable suspicion of underlying disease that might interfere with the conduct of the trial.
4. The subject has a history of hypersensitivity or allergies to dexlansoprazole, any component of dexlansoprazole or any PPI (including lansoprazole, omeprazole, rabeprazole, pantoprazole, or esomeprazole) or antacids.
5. 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 Medication section of the study protocol.
6. The subject has a condition that may require inpatient surgery during the course of the study.
7. The subject has known history of Barrett’s esophagus with dysplastic changes in the esophagus.
8. The subject has history of eosinophilic esophagitis (EoE) endoscopic or histologic findings suggestive of EoE (>15 eosinophils per high-powered field [HPF])
9. The subject has history of celiac disease, tests positive for tissue transglutaminase (tTG) antibody or confirmed disease by histology.
10. The subject has history of inflammatory bowel disease, or irritable bowel syndrome.
11. The subject has active gastric or duodenal ulcers within 4 weeks prior to Day -1.
12. The subject requires dilatation of esophageal strictures and/or strictures preventing passage of the endoscope during the screening endoscopy. Schatzki’s ring (a ring of mucosal tissue near the lower esophageal sphincter) is acceptable.
13. A female subject who has reached menarche.
14. The subject is known to be positive for the human immunodeficiency virus (HIV).
15. The subject has current or historical evidence of Zollinger-Ellison syndrome or other hypersecretory condition.
16. The subject has a history of gastric, duodenal, or esophageal surgery except simple oversew of an ulcer. A history of gastric tube and/or percutaneous endoscopic gastrostomy (PEG) placement is allowed.
17. The subject had an acute upper gastrointestinal hemorrhage within 4 weeks prior to endoscopy.
18. The subject has donated or 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 drug.
19. The subject has a known history of alcohol abuse or illegal drug use within the past 12 months prior to the first dose of study drug.
20. The subject has any screening abnormal laboratory value that suggests a clinically significant underlying disease or condition that may prevent the subject from entering the study; or the subject has: creatinine >1.5 mg/dL, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 times the upper limit of normal (×ULN), or total bilirubin >2.0 mg/dL with AST/ALT elevated above the limits of normal values.
21. The subject 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 and assent (as applicable) under duress. Students of the institution/research facility who are under the supervision of, or in a subordinate role to, the investigator are also ineligible.
22. The subject, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
23. The subject has participated in another clinical study and/or has received any investigational compound within 30 days prior to Screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of days without hurting or burning in the stomach, chest or throat over the 12 weeks of treatment. |
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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) |
1) The proportion of subjects with Hetzel-Dent (HD) Grade 0 at Week 12 among subjects with HD classification scale Grade 1 and Histologic Features of Reflux Esophagitis (HFRE) Grade ≤2 at Baseline.
2) Percentage of days without hurting or burning in the stomach, chest or throat in children aged 9 to 11 years over the 12 weeks of treatment.
3) Percentage of days without hurting or burning in the stomach, chest or throat in children aged 1 to 8 years over the 12 weeks of treatment.
4) Percentage of days without vomiting over the 12 weeks of treatment.
5) Percentage of days food did not come up from stomach to mouth over the 12 weeks of treatment.
6) Percentage of days without trouble eating over the 12 weeks of treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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) | 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) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 |
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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 | 15 |
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 |
Belgium |
Brazil |
Israel |
Italy |
Mexico |
Poland |
Portugal |
United States |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |