Clinical Trials Register

Summary
EudraCT Number:	2012-001681-15
Sponsor's Protocol Code Number:	TAK-390MR_207
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2012-001681-15

A.3

Full title of the trial

A Phase 2 Multicenter, 36-Week Study to Assess the Safety and Effectiveness of Daily Oral Administration of Dexlansoprazole Delayed-Release Capsules for Healing of Erosive Esophagitis and Maintenance of Healed Erosive Esophagitis and Relief of Heartburn, in Adolescent Subjects Aged 12 to 17 Years

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study to assess safety and effectiveness of Dexlansoprazole capsules in treatment of acid reflux damage to esophagus and heartburn relief in subjects between 12 and 17 years of age.

A.4.1

Sponsor's protocol code number

TAK-390MR_207

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Takeda Global Research & Development Centre (Europe) Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Takeda Global Research & Development Centre (Europe) Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Takeda Global Research & Development Centre (Europe) Ltd
B.5.2	Functional name of contact point	Program Manager
B.5.3	Address:
B.5.3.1	Street Address	61 Aldwych
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC2B 4AE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0044 020 3116 8000
B.5.5	Fax number	0044 020 3116 8199
B.5.6	E-mail	clinicaloperations@tgrd.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Dexlansoprazole delayed-release capsules (Dexilant)
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda Pharmaceuticals U.S.A., Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dexlansoprazole delayed-release capsules
D.3.2	Product code	TAK-390MR
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dexlansoprazole
D.3.9.1	CAS number	138530-94-6
D.3.9.2	Current sponsor code	TAK-390
D.3.9.3	Other descriptive name	DEXLANSOPRAZOLE
D.3.9.4	EV Substance Code	SUB31929
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Dexlansoprazole delayed-release capsules (Dexilant)
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda Pharmaceuticals U.S.A., Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dexlansoprazole delayed-release capsules
D.3.2	Product code	TAK-390MR
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dexlansoprazole
D.3.9.1	CAS number	138530-94-6
D.3.9.3	Other descriptive name	DEXLANSOPRAZOLE
D.3.9.4	EV Substance Code	SUB31929
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Heartburn and Erosive Esophagitis in Adolescent Subjects

E.1.1.1

Medical condition in easily understood language

Heartburn and inflammation/swelling/irritation of the esophagus in Adolescent Subjects

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	LLT
E.1.2	Classification code	10018203
E.1.2	Term	GERD
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10019326
E.1.2	Term	Heartburn
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10063657
E.1.2	Term	Erosive esophagitis
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

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.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

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 7 days.
5. The subject has endoscopic evidence of EE (LA Grade A-D) based on the screening endoscopy.
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.

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 per the CLO test results.
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 have acquired immunodeficiency syndrome.
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, or is unwilling to agree to abstain from alcohol or illegal drug use throughout the study.
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.

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.

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.

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.

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

E.8.7

Trial has a data monitoring committee

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

As per protocol

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1