E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heartburn and Erosive Esophagitis in Adolescent Subjects |
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E.1.1.1 | Medical condition in easily understood language |
Heartburn and inflammation/swelling/irritation of the esophagus in Adolescent Subjects |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018203 |
E.1.2 | Term | GERD |
E.1.2 | System Organ Class | 100000004856 |
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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 |
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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 |
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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 once-daily oral administration of dexlansoprazole delayed release capsules 60 mg for 8 weeks in adolescent subjects, aged 12 to 17 years, with EE.
To assess the safety and effectiveness of dexlansoprazole delayed- release capsules 30 mg compared to matching placebo for 16 weeks in adolescent subjects for the maintenance of healed EE and relief of heartburn. |
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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 |
1. In the opinion of the investigator, the subject and parent(s) or legal guardian are capable of understanding and complying with protocol requirements.
2. Prior to any study-specific procedures being performed, the informed consent and the assent form, according to local country requirements, must be signed and dated by parent(s) or legal guardian and by the subject respectively.
3. The subject has a medical history of symptoms of GERD for at least 3 months prior to Screening (signed informed consent form and assent, if applicable) as assessed by the investigator.
4. The subject has met the electronic diary qualification criteria as assessed by the electronic daily diary defined as follows: heartburn (burning or hurting in your throat, chest, or stomach) on at least 3 of any 7 days. (Note: If an endoscopy done within 1 week prior to signing informed consent and assent is used to confirm diagnosis of EE, the subject does not need to meet this criterion).
5. The subject has endoscopic evidence of EE (LA Grade A-D) based on the screening endoscopy performed either during the Screening Period or within 1 week prior to signing informed consent and assent.
6. The subject is male or female and aged 12 to 17 years, inclusive.
7. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception* from signing of informed consent and assent throughout the duration of the study and for 30 days after last dose of study medication.
8. A female subject of childbearing potential who is or may become sexually active agrees to routinely use adequate contraception* from the time of signing the informed consent and assent until 30 days after the last dose of study medication.
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E.4 | Principal exclusion criteria |
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 clinically significant, uncontrolled 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 co-existing disease affecting the esophagus (eg, esophageal varices, scleroderma, viral or fungal infection, or esophageal stricture), history of radiation therapy or cryotherapy to the esophagus, caustic or physiochemical trauma such as sclerotherapy to the esophagus.
3. The subject has known history of Barrett’s with dysplastic changes in the esophagus.
4. The subject has a known history of eosinophilic esophagitis (EoE) or endoscopic findings suggestive of EoE.
5. The subject has a history of celiac disease or subject tests positive for tTG antibody.
6. The subject has active gastric or duodenal ulcers within 4 weeks prior to Day -1.
7. Subject has any finding 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.
8. Subject has taken any PPI within 1 week (7 days) prior to the Screening Visit.
9. Subject tests positive for H. pylori.
10. The subject has a history of hypersensitivity or allergies to dexlansoprazole or any component of dexlansoprazole or any PPI (including lansoprazole, omeprazole, rabeprazole, pantoprazole, or esomeprazole) or antacid containing Mg(OH)2 and/or Al(OH)3 or simethicone.
11. The subject is required to take excluded medications or it is anticipated that the subject will require treatment with at least one of the disallowed concomitant medications during the study evaluation period as specified in the Excluded Medications and Treatments Section 7.3.
12. The subject has a history of malignant disease (except basal cell carcinoma) within 5 years prior to Screening.
13. The subject has a condition that may require inpatient surgery during the course of the study.
14. 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.
15. The subject is known to be human immunodeficiency virus (HIV) positive.
16. The subject has current or clinical history of Zollinger-Ellison syndrome or other hypersecretory condition.
17. 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.
18. The subject had an acute upper gastrointestinal hemorrhage within 4 weeks prior to endoscopy.
19. The subject has donated or lost 300 mL blood volume, undergone plasmapheresis, or has had a transfusion of any blood product within 90 days prior to the first dose of study drug.
20. 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.
21. The subject has any Screening Visit 1 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.
22. If female, the subject is pregnant or lactating or intending to become pregnant before, during or within 30 days after last dose of study medication; or intending to donate ova during such time period.
23. If male, the subject intends to donate sperm during the course of this study or within 30 days after last dose of study drug.
24. The subject, subject’s Parent(s) or 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 and assent 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.
25. The subject or subject’s Parent(s) or Legal Guardian, in the opinion of the investigator, is unlikely to comply with the protocol requirements or is unsuitable for any other reason.
26. 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) |
1. Treatment-emergent adverse events experienced by ≥5% of subjects during the 8-week Treatment Period for healing of Erosive Esophagitis.
2. Treatment-emergent adverse events experienced by ≥5% of subjects during the 16-week double-blind Treatment Period for maintenance of healed Erosive Esophagitis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Ongoing over the first 8 weeks
2. Ongoing over the 24 week period. |
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E.5.2 | Secondary end point(s) |
1. The percentage of subjects with healing of Erosive Esophagitis by Week 8 as assessed by endoscopy.
2. The percentage of subjects who maintain healing of Erosive Esophagitis from Week 8 to Week 24 among the subjects who were healed at Week 8 as assessed by endoscopy.
3. The percentage of days with neither daytime nor nighttime heartburn over the first 8 weeks of treatment as assessed by electronic daily diary.
4. The percentage of days with neither daytime nor nighttime heartburn over Weeks 8 to 24 as assessed by electronic daily diary among the subjects who were healed at Week 8. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. By week 8
2. After 24 weeks
3. Over first 8 weeks
4. Over weeks 8 to 24 |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
An open label healing phase followed by a double blind maintenance phase |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Bulgaria |
Hungary |
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 | 10 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |