Efficacy and Safety of Dexlansoprazole in Healing and Maintaining Healing of Erosive Esophagitis

• Sponsor: Takeda (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02873702
• Collaborator: (none)
• Enrollment: 37
• Locations: 25
• Arms: 4
• Actual Duration (Months): 10.5
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy of dexlansoprazole compared to lansoprazole in healing erosive esophagitis (EE) in Chinese participants.

Condition or Disease	Intervention/Treatment	Phase
Erosive Esophagitis	Drug: Dexlansoprazole; Drug: Lansoprazole; Drug: Placebo	Phase 3

Detailed Description

The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested to treat people who have EE. This study will look at erosive esophageal healing in people who take dexlansoprazole.

The study will enroll approximately 450 participants. Participants will be randomly assigned to one of the two treatment groups with 1:1 ratio-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Dexlansoprazole 60 mg

• Lansoprazole 30 mg

After 8 weeks of treatment, participants will be evaluated to assess esophageal healing. If the EE is healed participants will be randomly assigned to one of two different treatment groups with 1:1 ratio:

• Dexlansoprazole 30 mg

• Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient.

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

This multi-center trial will be conducted in China. The overall time to participate in this study is up to 39 weeks. Participants will make 7 visits to the clinic, and will be contacted by telephone 5 to 10 days after last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study to Evaluate the Efficacy and Safety of Dexlansoprazole (60 mg QD) and an Active Comparator, Lansoprazole (30 mg QD) on Healing of Erosive Esophagitis, and Maintenance of Healing in Subjects With Healed Erosive Esophagitis With Dexlansoprazole (30 mg QD) and Placebo
• Actual Study Start Date: Dec 21, 2016
• Actual Primary Completion Date: Oct 16, 2017
• Actual Study Completion Date: Nov 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healing Period: Dexlansoprazole 60 mg Dexlansoprazole 60 milligram (mg), delayed-release capsules, orally, once daily for up to 8 weeks in the Healing Period.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsules.
Experimental: Healing Period: Lansoprazole 30 mg Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Drug: Lansoprazole; Lansoprazole capsules.
Experimental: Maintenance Period: Dexlansprazole 30 mg Participants who will be healed at Week 8 will be randomized to receive dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsules.
Experimental: Maintenance Period: Placebo Participants who will be healed at Week 8 will be randomized to receive dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period.	Drug: Placebo; Dexlansoprazole placebo-matching capsules.

Outcome Measures

Primary Outcome Measures

1. Healing Period: Percentage of Participants With Complete Healing of EE at Week 8 [Week 8]

   Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the Los Angeles (LA) classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (>=1 mucosal break no longer than 5 millimeter [mm] that does not extend between the tops of 2 mucosal folds); Grade B (>=1 mucosal break greater than [>] 5 mm that does not extend between the tops of 2 mucosal folds); Grade C (>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves <75 percent (%) of the circumference); Grade D (>=1 mucosal break which involves >=75% of the circumference). Healing is defined as LA Grade O.

Secondary Outcome Measures

1. Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6 [Month 6]

   Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the LA classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (>=1 mucosal break no longer than 5 mm that does not extend between the tops of 2 mucosal folds); Grade B (>=1 mucosal break >5 mm that does not extend between the tops of 2 mucosal folds); Grade C (>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves <75% of the circumference); Grade D (>=1 mucosal break which involves >=75% of the circumference). Healing is defined as LA Grade O.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Has endoscopically confirmed EE as defined by the LA Classification Grading System (A-D).

Exclusion Criteria:

1. Participant is required to take excluded medications, or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study evaluation period.

2. Has a hypersensitivity to any proton pump inhibitor (PPI) (including, but not limited to, lansoprazole, omeprazole, rabeprazole, pantoprazole, esomeprazole or ilaprazole), any component of dexlansoprazole, or antacid (example, magnesium trisilicate or similar antacid).

3. Had a history of cancer, (except basal cell carcinoma of the skin), that has not been in remission for at least 5 years prior to Screening.

4. Has a known history or any suspicious Barrett's esophagus with dysplastic changes seen during screening endoscopy.

5. Developed acute upper gastrointestinal bleeding, gastric ulcer (a mucosal defect with white coating) or duodenal ulcer (a mucosal defect with white coating), within 30 days before the start of the Screening Visit (with the possible inclusion of those with gastric or duodenal erosion). The participant requires chronic use (>12 doses per month) of non steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) NSAIDs within 30 days prior to the Screening Period and throughout the study.

6. Has comorbidities that could affect the esophagus (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal strictures); a history of radiotherapy or cryotherapy of the esophagus; and a history of corrosive or physiochemical injury (with the possible inclusion in the study of those with Schatzki's ring).

7. Has a history of surgical procedures that may affect the esophagus (example, fundoplication and mechanical dilatation for esophageal strictures) or a history of gastric or duodenal surgery other than endoscopic removal of benign polyps.

8. Participant is known to have the acquired immunodeficiency syndrome (AIDS) or hepatitis, including hepatitis virus carriers (that is, hepatitis B surface antigen HBs-antigen (HBsAg) positive or hepatitis C virus (HCV)-antibody positive).

9. Has current Zollinger-Ellison syndrome (gastric acid hyper secretion) or a history of gastric acid hypersecretion.

10. Participant is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study.

11. Has donated or lost >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.

12. Has a history of alcohol or drug abuse (defined as any illicit drug use), or drug addiction in the 12 months prior to Screening.

13. The participant with positive serology result of Helicobacter pylori (H. pylori) that needs eradication therapy during the study participation period as anticipated by the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University First Hospital	Beijing	Beijing	China	100032
2	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
3	Chongqing Three Gorges Central Hospital	Chong Qing	Chong Qing	China	404100
4	Zhongshan Hospital Xiamen University	Xia Men	Fu Jian	China	361004
5	The People's Hospital of Guangxi Zhuang Autonomous Region	Nan Ning	Guang XI	China	530022
6	Affilicated Hospital of Guilin Medical University	Hai Kou	Gui Lin	China	570100
7	Hebei General Hospital	Shijiazhuang	Hebei	China	050051
8	Taihe Hospital	Shi Yan	Hu Bei	China	442000
9	Central Hospital of Wuhan	Wuhan	Hu Bei	China	430000
10	Puai Hospital Of Wuhan City	Wuhan	Hu Bei	China	430000
11	The Third Hospital of Changsha	Chang Sha	Hu Nan	China	410015
12	Zhongda Hospital Southeast	Nan Jing	Jiang Su	China	210009
13	Affiliated Hospital of Jiangsu University	Wu XI	Jiang Su	China	212001
14	Wuxi people's hospital	Wu XI	Jiang Su	China	214023
15	The First Hospital of Jilin University	Changchun	Jilin	China	130000
16	Shengjing Hospital of China Medical University	Shenyang	Liaoning	China	110004
17	Binzhou Medical University Hospital	Binzhou	Shandong	China	256603
18	Jinan Central Hospital	Jinan	Shandong	China	250013
19	Liaocheng Hospital	Liaocheng	Shandong	China	252000
20	The Affiliated Hospital of Qingdao University	Qingdao	Shandong	China	266003
21	Renji Hospital Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	20001
22	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
23	The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
24	West China Hospital,Sichuan University	Cheng Du	Si Chuang	China	610041
25	Tianjin People's Hospital	Tianjin	Tianjin	China	300121

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Feb 20, 2017
• Statistical Analysis Plan - Feb 14, 2018

More Information

Additional Information:

• Dexlansoprazole Package Insert

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02873702
• Other Study ID Numbers: TAK-390MR_301; U1111-1142-0320
• First Posted: Aug 19, 2016
• Last Update Posted: Feb 22, 2019
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Esophagitis; Lansoprazole; Dexlansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 8 investigative sites in China from 21 December 2016 to 06 November 2017.
Pre-assignment Detail	Participants with erosive esophagitis (EE) were enrolled to receive: lansoprazole 30 milligram (mg) or dexlansoprazole 60 mg in Healing Period and dexlansoprazole 30 mg or Placebo in Maintenance Period. Study was terminated since compound was not expected to provide sufficient additional benefit to participants over currently available therapies.

Arm/Group Title	Healing Period: Lansoprazole 30 mg	Healing Period: Dexlansoprazole 60 mg	Maintenance Period: Placebo	Maintenance Period: Dexlansoprazole 30 mg
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.	Dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.
Period Title: Healing Period (up to Week 8)
STARTED	20	17	0	0
COMPLETED	19	16	0	0
NOT COMPLETED	1	1	0	0
Period Title: Healing Period (up to Week 8)
STARTED	0	0	8	8
COMPLETED	0	0	1	6
NOT COMPLETED	0	0	7	2

Baseline Characteristics

Arm/Group Title	Healing Period: Lansoprazole 30 mg	Healing Period: Dexlansoprazole 60 mg	Total
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Total of all reporting groups
Overall Participants	20	17	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.4 (14.35)	47.4 (11.03)	48.4 (12.80)
Sex: Female, Male (Count of Participants)
Female	6 30%	3 17.6%	9 24.3%
Male	14 70%	14 82.4%	28 75.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	20 100%	17 100%	37 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
China	20 100%	17 100%	37 100%
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	166.28 (8.091)	167.82 (8.346)	166.99 (8.131)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	64.73 (10.002)	69.44 (11.190)	66.89 (10.683)
Baseline Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	23.310 (2.2623)	24.606 (3.5321)	23.905 (2.9452)
BMI Categories (Count of Participants)
Less than (<) 25 kg/m^2	15 75%	9 52.9%	24 64.9%
25 to <30 kg/m^2	5 25%	7 41.2%	12 32.4%
Greater than or equal to (>=) 30 kg/m^2	0 0%	1 5.9%	1 2.7%

Outcome Measures

1. Primary Outcome

Title	Healing Period: Percentage of Participants With Complete Healing of EE at Week 8
Description	Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the Los Angeles (LA) classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (>=1 mucosal break no longer than 5 millimeter [mm] that does not extend between the tops of 2 mucosal folds); Grade B (>=1 mucosal break greater than [>] 5 mm that does not extend between the tops of 2 mucosal folds); Grade C (>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves <75 percent (%) of the circumference); Grade D (>=1 mucosal break which involves >=75% of the circumference). Healing is defined as LA Grade O.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

The FAS-H included all randomized participants who had documented EE at screening and had received at least 1 dose of study drug during the first 8 weeks of treatment.

Arm/Group Title	Healing Period: Lansoprazole 30 mg	Healing Period: Dexlansoprazole 60 mg
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.
Measure Participants	20	17
Number [percentage of participants]	85.0 425%	82.4 484.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healing Period: Lansoprazole 30 mg, Healing Period: Dexlansoprazole 60 mg
	Comments	Healing Period: Dexlansoprazole 60 mg versus Healing Period: Lansoprazole 30 mg
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority to lansoprazole if the lower bound of confidence interval (CI) for the treatment difference is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-2.65
	Confidence Interval	(2-Sided) 95%; -26.59 to 21.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6
Description	Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the LA classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (>=1 mucosal break no longer than 5 mm that does not extend between the tops of 2 mucosal folds); Grade B (>=1 mucosal break >5 mm that does not extend between the tops of 2 mucosal folds); Grade C (>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves <75% of the circumference); Grade D (>=1 mucosal break which involves >=75% of the circumference). Healing is defined as LA Grade O.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

The full analysis set for the maintenance period (FAS-M) included all participants with healed EE by week 8 who were randomized and received at least 1 dose of study drug during 6 months of maintenance treatment.

Arm/Group Title	Maintenance Period: Placebo	Maintenance Period: Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.	Dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.
Measure Participants	8	8
Number [percentage of participants]	0 0%	25 147.1%

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 5 to 10 days (Day 190) after the last dose of double-blind 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	Healing Period: Lansoprazole 30 mg		Healing Period: Dexlansoprazole 60 mg		Maintenance Period: Placebo		Maintenance Period: Dexlansoprazole 30 mg
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.		Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.		Dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.		Dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.
All Cause Mortality
	Healing Period: Lansoprazole 30 mg		Healing Period: Dexlansoprazole 60 mg		Maintenance Period: Placebo		Maintenance Period: Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Healing Period: Lansoprazole 30 mg		Healing Period: Dexlansoprazole 60 mg		Maintenance Period: Placebo		Maintenance Period: Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Healing Period: Lansoprazole 30 mg		Healing Period: Dexlansoprazole 60 mg		Maintenance Period: Placebo		Maintenance Period: Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/20 (75%)		7/17 (41.2%)		1/8 (12.5%)		5/8 (62.5%)
Cardiac disorders
Ventricular extrasystoles	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Eye disorders
Dry eye	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Gastrointestinal disorders
Diarrhoea	1/20 (5%)		2/17 (11.8%)		0/8 (0%)		0/8 (0%)
Gastric polyps	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Nausea	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Gastritis erosive	0/20 (0%)		0/17 (0%)		1/8 (12.5%)		0/8 (0%)
General disorders
Pyrexia	0/20 (0%)		1/17 (5.9%)		0/8 (0%)		0/8 (0%)
Infections and infestations
Upper respiratory tract infection	3/20 (15%)		2/17 (11.8%)		0/8 (0%)		1/8 (12.5%)
Viral upper respiratory tract infection	2/20 (10%)		0/17 (0%)		0/8 (0%)		1/8 (12.5%)
Urinary tract infection	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Injury, poisoning and procedural complications
Skin injury	0/20 (0%)		1/17 (5.9%)		0/8 (0%)		0/8 (0%)
Limb injury	0/20 (0%)		0/17 (0%)		0/8 (0%)		1/8 (12.5%)
Investigations
Alanine aminotransferase increased	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Blood urea increased	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Protein urine present	0/20 (0%)		0/17 (0%)		0/8 (0%)		2/8 (25%)
Metabolism and nutrition disorders
Hyperuricaemia	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Nervous system disorders
Dizziness	3/20 (15%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Headache	0/20 (0%)		1/17 (5.9%)		0/8 (0%)		0/8 (0%)
Renal and urinary disorders
Nephrolithiasis	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Haematuria	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Laryngeal discomfort	1/20 (5%)		0/17 (0%)		0/8 (0%)		0/8 (0%)
Oropharyngeal pain	1/20 (5%)		0/17 (0%)		0/8 (0%)		1/8 (12.5%)
Cough	0/20 (0%)		1/17 (5.9%)		0/8 (0%)		0/8 (0%)

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.