Safety and Efficacy of Dexlansoprazole Delayed-Release Capsules in Treating Symptomatic Non-Erosive Gastroesophageal Reflux Disease in Adolescents

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01642602
• Collaborator: (none)
• Enrollment: 104
• Locations: 65
• Arm: 1
• Duration (Months): 18
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the safety and effectiveness of once daily oral administration of dexlansoprazole delayed-release capsules in adolescent participants with symptomatic non-erosive gastroesophageal reflux disease (GERD).

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux Disease	Drug: Dexlansoprazole	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Open-Label, Multicenter, 4-Week Study to Assess the Safety and Effectiveness of Daily Oral Administration of Dexlansoprazole Delayed-Release Capsules for Relief of Heartburn, in Adolescent Subjects Aged 12 to 17 Years With Symptomatic Non-Erosive Gastroesophageal Reflux Disease
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexlansoprazole 30 mg Dexlansoprazole 30 mg delayed-release capsules orally once daily for up to 4 weeks.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsules.; Other Names: Dexilant TAK-390MR

Outcome Measures

Primary Outcome Measures

1. Percent of Participants Who Experience Each Treatment Emergent Adverse Event Experienced by ≥5% of Participants While Receiving Dexlansoprazole During the 4 Week Treatment Period [4 weeks]

   A Treatment Emergent Adverse Event (TEAE) is defined as an Adverse Event (AE) that started or worsened on or after Study Day 1 (defined as first dose day), and no more than 30 days after the last dose of study drug.

Secondary Outcome Measures

1. The Percentage of Days With Neither Daytime Nor Nighttime Heartburn Over the 4 Weeks of Treatment [4 weeks]

   Participants documented the presence or absence and the degree to which daytime and nighttime heartburn symptoms hurt daily in an electronic daily diary.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 GERD for at least 3 months prior to Screening (signed informed consent 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.

5. The participant has non-erosive GERD with no evidence of definite endoscopic esophageal mucosal breaks as described in the Los Angeles Classification of Esophagitis at 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, or 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 a 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 the participant tests positive for 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 PPI within 1 week (7 days) prior to the Screening Visit.

9. 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.

10. 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.

11. The participant has a history of malignant disease (except basal cell carcinoma) within 5 years prior to Screening.

12. The participant has a condition that may require inpatient surgery during the course of the study.

13. 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.

14. The participant is known to be positive for human immunodeficiency virus (HIV).

15. The participant has current or clinical history of Zollinger-Ellison syndrome or other hypersecretory condition.

16. 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.

17. The participant had an acute upper gastrointestinal hemorrhage within 4 weeks prior to endoscopy.

18. 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.

19. 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.

20. 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.

21. 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.

22. If male, the participant intends to donate sperm during the course of this study or within 30 days after last dose of study drug.

23. 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.

24. 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.

25. The participant has participated in another clinical study and/or has received any investigational compound within 30 days prior to Screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States
2		Mobile	Alabama	United States
3		Phoenix	Arizona	United States
4		Tucson	Arizona	United States
5		Anaheim	California	United States
6		Los Angeles	California	United States
7		San Francsco	California	United States
8		Centennial	Colorado	United States
9		Thornton	Colorado	United States
10		Miami	Florida	United States
11		Atlanta	Georgia	United States
12		Chicago	Illinois	United States
13		Park Ridge	Illinois	United States
14		Indianapolis	Indiana	United States
15		Louisville	Kentucky	United States
16		Boston	Massachusetts	United States
17		Flint	Michigan	United States
18		Plymouth	Minnesota	United States
19		Jackson	Mississippi	United States
20		Kansas City	Missouri	United States
21		Mays Landing	New Jersey	United States
22		Brooklyn	New York	United States
23		Huntsville	North Carolina	United States
24		Toledo	Ohio	United States
25		Youngstown	Ohio	United States
26		Greenville	South Carolina	United States
27		Kingsport	Tennessee	United States
28		Ft. Worth	Texas	United States
29		Houston	Texas	United States
30		Laredo	Texas	United States
31		San Antonio	Texas	United States
32		Ogden	Utah	United States
33		Salt Lake City	Utah	United States
34		Fairfax	Virginia	United States
35		Norfolk	Virginia	United States
36		Bruxelles		Belgium
37		Passo Fundo	Rio Grande do Sul	Brazil
38		Porto Alegre	Rio Grande do Sul	Brazil
39		Santo Andre	Sao Paulo	Brazil
40		Santo André	Sao Paulo	Brazil
41		São José do Rio Preto	Sao Paulo	Brazil
42		Debrecen		Hungary
43		Györ		Hungary
44		Miskolc		Hungary
45		Nyiregyhaza		Hungary
46		Pecs		Hungary
47		Veszprem		Hungary
48		Bari		Italy
49		Messina		Italy
50		Roma		Italy
51		Mexico	Distrito Federal	Mexico
52		Monterrey	Nuevo León	Mexico
53		Culiacan	Sinaloa	Mexico
54		Bydgoszcz		Poland
55		Krakow		Poland
56		Rzeszow		Poland
57		Szczecin		Poland
58		Torun		Poland
59		Warszawa		Poland
60		Wroclaw		Poland
61		Amadora		Portugal
62		Braga		Portugal
63		Coimbra		Portugal
64		Lisboa		Portugal
65		Porto		Portugal

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda Global Research and Development Center, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Dexilant Package Insert

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01642602
• Other Study ID Numbers: TAK-390MR_206; U1111-1128-5977; 2012-001680-72
• First Posted: Jul 17, 2012
• Last Update Posted: Aug 6, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Takeda: Drug Therapy
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic; Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 36 sites in the United States, Belgium, Hungary, Italy, Poland, Portugal, Brazil, and Mexico from 22 June 2012 to 21 January 2014.
Pre-assignment Detail	Adolescent participants (male or female), aged 12 to 17 years (inclusive) with symptomatic non-erosive gastrointestinal reflux disease were enrolled in 1 group and received dexlansoprazole 30 mg orally once daily for up to 4 weeks.

Arm/Group Title	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole 30 mg delayed-release capsules orally once daily for up to 4 weeks.
Period Title: Overall Study
STARTED	104
COMPLETED	102
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole 30 mg delayed-release capsules orally once daily for up to 4 weeks.
Overall Participants	104
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.0 (1.50)
Age, Customized (participants) [Number]
12 to 14 years	34 32.7%
15 to 17 years	70 67.3%
Sex: Female, Male (Count of Participants)
Female	73 70.2%
Male	31 29.8%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	6 5.8%
White	95 91.3%
Multiracial	3 2.9%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	19 18.3%
Non-Hispanic and Latino	47 45.2%
Not Collected	38 36.5%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	61.60 (14.393)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	163.1 (7.58)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.02 (4.434)
Smoking Classification (participants) [Number]
Never Smoked	103 99%
Ex-smoker	1 1%
H pylori Status (participants) [Number]
Positive	14 13.5%
Negative	90 86.5%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants Who Experience Each Treatment Emergent Adverse Event Experienced by ≥5% of Participants While Receiving Dexlansoprazole During the 4 Week Treatment Period
Description	A Treatment Emergent Adverse Event (TEAE) is defined as an Adverse Event (AE) that started or worsened on or after Study Day 1 (defined as first dose day), and no more than 30 days after the last dose of study drug.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set: All participants who received at least 1 dose of study drug.

Arm/Group Title	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole 30 mg delayed-release capsules orally once daily for up to 4 weeks.
Measure Participants	104
Diarrhoea	6.7 6.4%
Headache	6.7 6.4%

2. Secondary Outcome

Title	The Percentage of Days With Neither Daytime Nor Nighttime Heartburn Over the 4 Weeks of Treatment
Description	Participants documented the presence or absence and the degree to which daytime and nighttime heartburn symptoms hurt daily in an electronic daily diary.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants who received at least 1 dose of study drug and had post-baseline data (and baseline data if applicable) for the efficacy variable.

Arm/Group Title	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole 30 mg delayed-release capsules orally once daily for up to 4 weeks.
Measure Participants	104
Median (Full Range) [Percentage of days]	47.3 (32.18)

Adverse Events

Time Frame	A Treatment Emergent Adverse Event (TEAE) is defined as an Adverse Event (AE) that started or worsened on or after Study Day 1 (defined as first dose day), and no more than 30 days after the last dose of study drug
Adverse Event Reporting Description	At each visit, the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole 30 mg delayed-release capsules orally once daily for up to 4 weeks.
All Cause Mortality
	Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events
Total	0/104 (0%)
Other (Not Including Serious) Adverse Events
	Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events
Total	14/104 (13.5%)
Gastrointestinal disorders
Diarrhoea	7/104 (6.7%)
Nervous system disorders
Headache	7/104 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.