Clinical trial NCT01642615: Safety and Efficacy of Dexlansoprazole Delayed-Release Capsules for Healing of Erosive Esophagitis and Maintenance of Healed Erosive Esophagitis and Relief of Heartburn in Adolescents
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroesophageal Reflux Disease
Erosive Esophagitis
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-07-17
Enrollment: 63
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and effectiveness of treatment with once daily oral administration of dexlansoprazole delayed-release capsules in adolescents with erosive esophagitis (EE) and for maintenance of healed EE and relief of heartburn.

Detailed description: The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested to treat adolescents who have erosive esophagitis and heartburn and maintenance of healing of EE.

The study planned to enroll approximately 60 patients.

The study consisted of 3 periods:

1. Screening ((21 \[+5\] days)
2. Treatment (8 weeks for healing, 16 weeks for maintenance),
3. Post-Treatment Follow-up (up to 3 months).

During screening, participants used an electronic diary (eDiary) daily to document the presence of daytime and nighttime heartburn symptoms and the degree to which heartburn hurt (hereinafter referred to as severity), and to record their use of rescue medication (antacid).

During the first 8 week treatment period, all participants received dexlansoprazole 60 mg, once daily (QD). At the Week 8 visit, participants underwent endoscopy to assess healing of EE. Participants whose EE had not healed were discontinued from the study.

Participants whose EE had healed were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* dexlansoprazole 30 mg QD
* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

All participants were asked to take one tablet each morning without regard to food throughout the study. Throughout both phases of the Treatment Period, all participants continued to use the eDiary to document the presence or absence and severity of daytime and nighttime heartburn symptoms and the use of rescue medication.

This multi-center trial was conducted worldwide. The overall time to participate in this study was 39 weeks. Participants made multiple visits to the clinic, and were contacted by telephone during the study

Eligibility criteria: Inclusion Criteria:

1. In the opinion of the investigator, the participant 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 participant respectively.
3. The participant has a medical history of symptoms of Gastroesophageal Reflux Disease (GERD) for at least 3 months prior to Screening (signed informed consent form and assent, if applicable) as assessed by the investigator.
4. The participant 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.(Note: if an endoscopy done within 1 week of signing informed consent and assent is used to confirm diagnosis of EE, the subject does not need to meet this criterion).
5. The participant has endoscopic evidence of EE (LA Grade A-D) based on the screening endoscopy.
6. The participant is male or female and aged 12 to 17 years, inclusive.
7. A male participant 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 participant 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.

Exclusion Criteria:

1. Participant 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 participant to participate or potentially confound the study results.
2. The participant 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 participant has known history of Barrett's with dysplastic changes in the esophagus.
4. The participant has a known history of eosinophilic esophagitis (EoE) or endoscopic findings suggestive of EoE.
5. The participant has a history of celiac disease or participant tests positive for tissue transglutaminase (tTG) antibody.
6. The participant has active gastric or duodenal ulcers within 4 weeks prior to Day -1.
7. Participant 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. Participant has taken any proton pump inhibitor (PPI) within 1 week (7 days) prior to the Screening Visit.
9. Participant tests positive for H. pylori.
10. The participant 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 participant is required to take excluded medications or it is anticipated that the participant 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 participant has a history of malignant disease (except basal cell carcinoma) within 5 years prior to Screening.
13. The participant has a condition that may require inpatient surgery during the course of the study.
14. The participant 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 participant is known to be human immunodeficiency virus (HIV) positive.
16. The participant has current or clinical history of Zollinger-Ellison syndrome or other hypersecretory condition.
17. The participant 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 participant had an acute upper gastrointestinal hemorrhage within 4 weeks prior to endoscopy.
19. The participant 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 participant 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 participant has any Screening Visit 1 abnormal laboratory value that suggests a clinically significant underlying disease or condition that may prevent the participant from entering the study; or the participant 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 participant 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 participant intends to donate sperm during the course of this study or within 30 days after last dose of study drug.
24. The participant, participant'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 participant or participant'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 participant has participated in another clinical study and/or has received any investigational compound within 30 days prior to Screening.

Primary outcomes:
measure: Percentage of Participants Who Experience Each Treatment Emergent Adverse Event Experienced by ≥5% of Participants During the 8-week Healing Treatment Period
timeFrame: 8 weeks
measure: Percent of Participants Who Experience Each Treatment Emergent Adverse Event Experienced by ≥5% of Participants During the 16-week Maintenance Treatment Period
timeFrame: From Week 8 to Week 24
Secondary outcomes:
measure: Percentage of Participants With Healing of Erosive Esophagitis (EE) by Week 8
timeFrame: 8 weeks
measure: Percentage of Participants Who Maintain Healing of EE From Week 8 to Week 24
timeFrame: From Week 8 to Week 24
measure: Percent of Days With Neither Daytime Nor Nighttime Heartburn Over the First 8 Weeks of Treatment
timeFrame: 8 weeks
measure: Percent of Days With Neither Daytime Nor Nighttime Heartburn Over Weeks 8 to 24
timeFrame: Weeks 8 to 24
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francsco
country: United States
state: California
city: Centennial
country: United States
state: Colorado
city: Thornton
country: United States
state: Colorado
city: Chicago
country: United States
state: Illinois
city: Park Ridge
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Flint
country: United States
state: Michigan
city: Plymouth
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Kansas City
country: United States
state: Missouri
city: Mays Landing
country: United States
state: New Jersey
city: Brooklyn
country: United States
state: New York
city: Toledo
country: United States
state: Ohio
city: Youngstown
country: United States
state: Ohio
city: Greenville
country: United States
state: South Carolina
city: Kingsport
country: United States
state: Tennessee
city: Ft. Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Laredo
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Fairfax
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Bruxelles
country: Belgium
city: Passo Fundo
country: Brazil
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: Santo Andre
country: Brazil
state: Sao Paulo
city: Santo André
country: Brazil
state: Sao Paulo
city: São José do Rio Preto
country: Brazil
state: Sao Paulo
city: Debrecen
country: Hungary
city: Györ
country: Hungary
city: Miskolc
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Pecs
country: Hungary
city: Bari
country: Italy
city: Messina
country: Italy
city: Roma
country: Italy
city: Mexico
country: Mexico
state: Distrito Federal
city: Monterrey
country: Mexico
state: Nuevo León
city: Culiacan
country: Mexico
state: Sinaloa
city: Bydgoszcz
country: Poland
city: Krakow
country: Poland
city: Rzeszow
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Amadora
country: Portugal
city: Braga
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
Study officials:
affiliation: Takeda Global Research and Development Center, Inc.
name: Medical Director, Clinical Science
role: STUDY_DIRECTOR
References: