Effect of Dexlansoprazole 60 mg QD and 60 mg BID on Recurrence of Intestinal Metaplasia in Subjects Who Have Achieved Complete Eradication of Barrett's Esophagus With Radiofrequency Ablation

• Sponsor: Takeda (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02162758
• Collaborator: (none)
• Enrollment: 6
• Locations: 6
• Arms: 2
• Duration (Months): 21
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is designed to evaluate the effect of dexlansoprazole once daily (QD) and twice daily (BID) dosing on the recurrence of intestinal metaplasia (IM) in participants who achieved complete eradication of Barrett's esophagus (BE) with high-grade dysplasia (HGD) following radiofrequency ablation (RFA).

Condition or Disease	Intervention/Treatment	Phase
Barrett's Esophagus	Drug: Dexlansoprazole; Drug: Dexlansoprazole Placebo	Phase 2

Detailed Description

The drug being tested in this study is called dexlansoprazole. The purpose of this study is to evaluate the effect of 12 months of treatment with dexlansoprazole 60 mg QD or dexlansoprazole 60 mg BID on the recurrence of IM in participants who have achieved complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) with RFA. The study will enroll approximately 150 participants. Participants will be 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 60 mg once a day and placebo (this is a capsule that looks like the study drug but has no active ingredient) once a day

• Dexlansoprazole 60 mg twice a day.

All participants will be asked to take one capsule twice a day at the same time each day throughout the study.

This randomized, double-blind, multi-center, parallel group trial will be conducted in North America. The overall time to participate in this study is up to 13 months. Participants will make 5 visits to the clinic, and will undergo a safety follow-up assessment 30 days after the last dose of study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Phase 4 Study to Evaluate the Effect of Dexlansoprazole 60 mg QD and 60 mg BID on Recurrence of Intestinal Metaplasia in Subjects Who Have Achieved Complete Eradication of Barrett's Esophagus With Radiofrequency Ablation
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexlansoprazole 60 milligram (mg) QD Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole 60 mg placebo-matching capsules, orally, once daily for up to 12 months.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsules; Other Names: Dexilant ; Drug: Dexlansoprazole Placebo; Dexlansoprazole placebo-matching capsules
Experimental: Dexlansoprazole 60 mg BID Dexlansoprazole 60 mg, delayed-release capsules, orally, BID for up to 12 months.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsules; Other Names: Dexilant

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Recurrence of Intestinal Metaplasia (IM) [Month 12]

   Recurrence of IM was defined as an esophageal biopsy result indicating BE with or without dysplasia.

Secondary Outcome Measures

1. Percentage of Participants With Recurrence of IM With Dysplasia [Month 12]

   Recurrence of IM with dysplasia was defined as an esophageal biopsy result indicating BE with dysplasia.

2. Percentage of Participants With Erosive Esophagitis (EE) [Baseline up to Month 12]

   The severity of EE was classified into following grades: Grade A: one or more mucosal breaks no longer than 5 millimeter (mm), none of which extends between the tops of the mucosal folds; Grade B: one or more mucosal breaks more than 5 mm long, none of which extends between the tops of two mucosal folds; Grade C: mucosal breaks that extend between the tops of two or more mucosal folds, but which involve less than 75 percent (%) of the esophageal circumference; Grade D: mucosal breaks which involve at least 75% of the esophageal circumference.

3. Change From Baseline in the Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) Total Score [Baseline and Month 12]

   The GERD-HRQL score consisted of 10 questions, where participants were required to answer each question on a scale of 0 to 5 (0: no symptoms; 1: symptoms noticeable but not bothersome; 2: symptoms noticeable and bothersome but not every day; 3: symptoms bothersome every day; 4: symptoms affect daily activity; 5: symptoms are incapacitating to do daily activities). The total score was derived by simply adding the individual score of each question. The total score ranged from 0 to 50 where a higher score indicated more severe disease. The best possible total GERD-HRQL score was 0 (asymptomatic in all questions) and the worst possible score is 50 (incapacitated in all questions).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Is male or female and aged 18 to 80 years, inclusive.

2. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

3. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

4. Has a history of initial CEIM following radiofrequency ablation (RFA) for Barrett's esophagus with high-grade dysplasia or low grade dysplasia within the past 3 years.

5. Had attained CEIM within 18 months of receiving his or her first RFA treatment.

6. Has endoscopic and histologic confirmed evidence of CEIM prior to randomization.

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 throughout the duration of the study and for 12 weeks after last dose.

8. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

Exclusion Criteria:

1. 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. Had previous ablative therapy with a modality other than RFA for Barrett's esophagus (photodynamic therapy, multipolar electrical coagulation, argon plasma coagulation, or laser treatment) with the exception of up to 3 treatments of thermal/coagulation therapy for focal residual disease following otherwise successful RFA therapy.

3. Has a co-existing disease affecting the esophagus (example, erosive esophagitis, 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.

4. Has a known history of eosinophilic esophagitis or endoscopic findings suggestive of eosinophilic esophagitis.

5. Has active gastric or duodenal ulcers within 4 weeks prior to Day -1.

6. 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.

7. Has a history of hypersensitivity or allergies to dexlansoprazole or any component of dexlansoprazole or any proton pump inhibitor (PPI) (including lansoprazole, omeprazole, rabeprazole, pantoprazole, or esomeprazole) or antacid.

8. 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..

9. Has a history of malignant disease (except basal cell carcinoma) within 5 years prior to Screening.

10. Has a condition that may require inpatient surgery during the course of the study.

11. 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.

12. Is known to have acquired immunodeficiency syndrome.

13. Has current or clinical history of Zollinger-Ellison syndrome or other hypersecretory condition.

14. 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.

15. Had an acute upper gastrointestinal hemorrhage within 4 weeks prior to endoscopy.

16. Has donated or lost greater than or equal to (>=)300 milliliter (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.

17. 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.

18. 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.

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

20. 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.

21. In the opinion of the investigator, is unlikely to comply with the protocol requirements or is unsuitable for any other reason.

22. Has been previously randomized in this study and received at least one dose of double blind study drug treatment.

23. Has received any investigational compound within 30 days prior to Screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Jacksonville	Florida	United States	32216
2		Jacksonville	Florida	United States
3		Chapel Hill	North Carolina	United States	27599
4		Chapel Hill	North Carolina	United States
5		Knoxville	Tennessee	United States	37909
6		Knoxville	Tennessee	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02162758
• Other Study ID Numbers: DEX-P4-003; U1111-1152-6767
• First Posted: Jun 13, 2014
• Last Update Posted: May 11, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Barrett Esophagus; Recurrence; Metaplasia; Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 2 investigative sites in the United States from 16 July 2014 to 09 May 2016.
Pre-assignment Detail	Participants with a diagnosis of Barrett's esophagus (BE) who had achieved complete eradication of intestinal metaplasia (CEIM) with radiofrequency ablation (RFA) were enrolled in 1 of the 2 treatment groups: Dexlansoprazole 60 milligram (mg), once-daily (QD); Dexlansoprazole 60 mg, twice daily (BID).

Arm/Group Title	Dexlansoprazole 60 mg QD	Dexlansoprazole 60 mg BID
Arm/Group Description	Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole placebo-matching capsules, orally, QD for up to 12 months.	Dexlansoprazole 60 mg, capsules, orally, BID for up to 12 months.
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	2
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Dexlansoprazole 60 mg QD	Dexlansoprazole 60 mg BID	Total
Arm/Group Description	Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole placebo-matching capsules, orally, QD for up to 12 months.	Dexlansoprazole 60 mg, capsules, orally, BID for up to 12 months.	Total of all reporting groups
Overall Participants	3	3	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.3 (8.50)	67.7 (6.81)	69.0 (7.04)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	1 16.7%
Male	3 100%	2 66.7%	5 83.3%
Race/Ethnicity, Customized (participants) [Number]
Not Hispanic or Latino	3 100%	3 100%	6 100%
Race/Ethnicity, Customized (participants) [Number]
White	3 100%	3 100%	6 100%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	179.3 (4.04)	167.3 (15.53)	173.3 (12.09)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	96.80 (20.264)	88.83 (8.170)	92.82 (14.491)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	29.95 (4.992)	31.93 (3.212)	30.94 (3.908)
Smoking History (participants) [Number]
Never smoked	1 33.3%	0 0%	1 16.7%
Ever smoked	2 66.7%	3 100%	5 83.3%
Number of Smoking Years for Ever Smoked (participants) [Number]
16-20 years	1 33.3%	1 33.3%	2 33.3%
Greater than (>) 20 years	1 33.3%	2 66.7%	3 50%
Current Smoking Status (participants) [Number]
Non smoker	2 66.7%	3 100%	5 83.3%
Smoker	1 33.3%	0 0%	1 16.7%
Number of Packs Per Year (participants) [Number]
101-200 packs	1 33.3%	0 0%	1 16.7%
301-400 packs	1 33.3%	0 0%	1 16.7%
>400 packs	0 0%	1 33.3%	1 16.7%
Unknown	0 0%	2 66.7%	2 33.3%
Alcohol History (participants) [Number]
Never drank alcohol	2 66.7%	1 33.3%	3 50%
Drank alcohol	1 33.3%	2 66.7%	3 50%
Number of Drinking Years (participants) [Number]
>20 years	0 0%	1 33.3%	1 16.7%
Unknown	1 33.3%	1 33.3%	2 33.3%
Number of Drinks Per Week (participants) [Number]
0-5 drinks	0 0%	1 33.3%	1 16.7%
6-10 drinks	0 0%	1 33.3%	1 16.7%
>30 drinks	1 33.3%	0 0%	1 16.7%
Current Alcohol Status (participants) [Number]
Current drinker	0 0%	2 66.7%	2 33.3%
Non-drinker	3 100%	1 33.3%	4 66.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Recurrence of Intestinal Metaplasia (IM)
Description	Recurrence of IM was defined as an esophageal biopsy result indicating BE with or without dysplasia.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) population where Month 12 esophageal biopsy assessment was available. The ITT population included all randomized participants who had documented CEIM at screening and took at least 1 dose of study drug during the treatment period.

Arm/Group Title	Dexlansoprazole 60 mg QD	Dexlansoprazole 60 mg BID
Arm/Group Description	Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole placebo-matching capsules, orally, QD for up to 12 months.	Dexlansoprazole 60 mg, capsules, orally, BID for up to 12 months.
Measure Participants	3	2
Number [percentage of participants]	0 0%	50 1666.7%

2. Secondary Outcome

Title	Percentage of Participants With Recurrence of IM With Dysplasia
Description	Recurrence of IM with dysplasia was defined as an esophageal biopsy result indicating BE with dysplasia.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

The ITT population where Month 12 esophageal biopsy assessment was available. The ITT population included all randomized participants who had documented CEIM at screening and took at least 1 dose of study drug during the treatment period.

Arm/Group Title	Dexlansoprazole 60 mg QD	Dexlansoprazole 60 mg BID
Arm/Group Description	Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole placebo-matching capsules, orally, QD for up to 12 months.	Dexlansoprazole 60 mg, capsules, orally, BID for up to 12 months.
Measure Participants	3	2
Number [percentage of participants]	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Erosive Esophagitis (EE)
Description	The severity of EE was classified into following grades: Grade A: one or more mucosal breaks no longer than 5 millimeter (mm), none of which extends between the tops of the mucosal folds; Grade B: one or more mucosal breaks more than 5 mm long, none of which extends between the tops of two mucosal folds; Grade C: mucosal breaks that extend between the tops of two or more mucosal folds, but which involve less than 75 percent (%) of the esophageal circumference; Grade D: mucosal breaks which involve at least 75% of the esophageal circumference.
Time Frame	Baseline up to Month 12

Outcome Measure Data

Analysis Population Description

The ITT population where EE assessment was available. The ITT population included all randomized participants who had documented CEIM at screening and took at least 1 dose of study drug during the treatment period.

Arm/Group Title	Dexlansoprazole 60 mg QD	Dexlansoprazole 60 mg BID
Arm/Group Description	Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole placebo-matching capsules, orally, QD for up to 12 months.	Dexlansoprazole 60 mg, capsules, orally, BID for up to 12 months.
Measure Participants	3	2
Number [percentage of participants]	0 0%	0 0%

4. Secondary Outcome

Title	Change From Baseline in the Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) Total Score
Description	The GERD-HRQL score consisted of 10 questions, where participants were required to answer each question on a scale of 0 to 5 (0: no symptoms; 1: symptoms noticeable but not bothersome; 2: symptoms noticeable and bothersome but not every day; 3: symptoms bothersome every day; 4: symptoms affect daily activity; 5: symptoms are incapacitating to do daily activities). The total score was derived by simply adding the individual score of each question. The total score ranged from 0 to 50 where a higher score indicated more severe disease. The best possible total GERD-HRQL score was 0 (asymptomatic in all questions) and the worst possible score is 50 (incapacitated in all questions).
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who had documented CEIM at screening and took at least 1 dose of study drug during the treatment period.

Arm/Group Title	Dexlansoprazole 60 mg QD	Dexlansoprazole 60 mg BID
Arm/Group Description	Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole placebo-matching capsules, orally, QD for up to 12 months.	Dexlansoprazole 60 mg, capsules, orally, BID for up to 12 months.
Measure Participants	3	3
Baseline	7.3 (10.21)	12.0 (10.00)
Change at Month 12	-3.0 (3.00)	-11.0 (8.54)

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after last dose of study drug (Month 13).
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 60 mg QD		Dexlansoprazole 60 mg BID
Arm/Group Description	Dexlansoprazole 60 mg, delayed-release capsules, orally, QD and dexlansoprazole placebo-matching capsules, orally, QD for up to 12 months.		Dexlansoprazole 60 mg, capsules, orally, BID for up to 12 months.
All Cause Mortality
	Dexlansoprazole 60 mg QD		Dexlansoprazole 60 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexlansoprazole 60 mg QD		Dexlansoprazole 60 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		2/3 (66.7%)
Musculoskeletal and connective tissue disorders
Worsening of back pain	1/3 (33.3%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia	0/3 (0%)		1/3 (33.3%)
Vascular disorders
Hypotension	0/3 (0%)		1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Dexlansoprazole 60 mg QD		Dexlansoprazole 60 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/3 (66.7%)
Cardiac disorders
Tachycardia	0/3 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Dyspepsia	2/3 (66.7%)		0/3 (0%)
General disorders
Pyrexia	0/3 (0%)		1/3 (33.3%)
Infections and infestations
Pneumonia	1/3 (33.3%)		1/3 (33.3%)
Sepsis	0/3 (0%)		1/3 (33.3%)
Metabolism and nutrition disorders
Hypokalaemia	0/3 (0%)		1/3 (33.3%)
Psychiatric disorders
Mental status changes	0/3 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/3 (0%)		1/3 (33.3%)
Hypoxia	0/3 (0%)		1/3 (33.3%)

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.