Efficacy and Safety of Dexlansoprazole on Heartburn Relief in Chinese Patients

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02873689
• Collaborator: (none)
• Enrollment: 217
• Locations: 25
• Arms: 2
• Actual Duration (Months): 15.7
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of dexlansoprazole compared to placebo in relief of daytime and nighttime heartburn over 4 weeks in Chinese participants with symptomatic non-erosive Gastroesophageal Reflux Disease (GERD).

Condition or Disease	Intervention/Treatment	Phase
Heartburn; Gastroesophageal Reflux Disease	Drug: Dexlansoprazole; Drug: Placebo	Phase 3

Detailed Description

The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested to treat heartburn in people who have non-erosive gastroesophageal reflux disease (GERD). This study will look at heartburn relief in people who take dexlansoprazole.

The study will enroll approximately 200 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 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, and will be asked to record any time they have heartburn symptoms in a diary.

This multi-center trial will be conducted in China. The overall time to participate in this study is up to 7 weeks. Participants will make 4 visits to the clinic, and will be contacted by telephone 5 to 10 days after the last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Double-blind Study to Evaluate the Efficacy and Safety of Dexlansoprazole (30 mg QD) Compared to Placebo on Heartburn Relief in Subjects With Symptomatic Nonerosive Gastroesophageal Reflux Disease (GERD)
• Actual Study Start Date: Dec 27, 2016
• Actual Primary Completion Date: Mar 14, 2018
• Actual Study Completion Date: Apr 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexlansoprazole 30 mg Dexlansoprazole 30 mg, delayed-release capsule, orally, once daily for up to 4 weeks.	Drug: Dexlansoprazole; Dexlansoprazole delayed-release capsule
Experimental: Placebo Dexlansoprazole placebo-matching capsules, orally, once daily for up to 4 weeks.	Drug: Placebo; Dexlansoprazole placebo-matching capsules

Outcome Measures

Primary Outcome Measures

1. Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment [Up to Week 4]

   The percentage of days with neither daytime nor nighttime heartburn was equal to (=) (the days that were heartburn-free during the treatment period) / (total number of days for which either a daytime or nighttime result was marked during treatment period)*100 percent (%).

Secondary Outcome Measures

1. Percentage of Days Without Nighttime Heartburn During Treatment [Up to Week 4]

   The percentage of days without nighttime heartburn was = (the days that were heartburn-free during the treatment period) / (total number of days for which nighttime result was marked during treatment period)*100%.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Participants identifying their main symptom as a burning feeling in the mid-epigastric area and/or chest area (that is, heartburn).

2. Must have a history of symptomatic GERD for 6 months or longer prior to Screening with GERD symptoms that were responsive to acid-suppressive therapy.

3. Must have episodes of heartburn for 4 or more days during the 7 days prior to Day -1 as recorded in the eDiary.

Exclusion Criteria:

1. Has 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.

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

3. Participant 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 (greater than [>] 12 doses per month) of nonsteroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) NSAIDs within 30 days prior to the Screening Period and throughout the study.

4. 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).

5. 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.

6. Has erosive esophagitis (EE) as shown by endoscopy, during the Screening Period.

7. Is known to have 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).

8. Has current or historical evidence of Zollinger-Ellison syndrome or a history of gastric acid hypersecretion.

9. Is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study.

10. 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.

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

12. 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)

• Statistical Analysis Plan - Dec 7, 2018
• Study Protocol - Feb 20, 2017

More Information

Additional Information:

• Dexlansoprazole Package Insert

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02873689
• Other Study ID Numbers: TAK-390MR_302; U1111-1171-1002
• First Posted: Aug 19, 2016
• Last Update Posted: Jul 5, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Gastroesophageal Reflux; Heartburn; Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 20 investigative sites in China from 27 December 2016 to 19 April 2018.
Pre-assignment Detail	Participants with diagnosis of symptomatic nonerosive gastroesophageal reflux disease (GERD) were enrolled in 1 of the 2 treatment groups: to receive dexlansoprazole 30 mg or placebo.

Arm/Group Title	Placebo	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole placebo-matching capsule, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsule, orally, once daily for up to 4 weeks.
Period Title: Overall Study
STARTED	109	108
Treated	108	107
COMPLETED	102	103
NOT COMPLETED	7	5

Baseline Characteristics

Arm/Group Title	Placebo	Dexlansoprazole 30 mg	Total
Arm/Group Description	Dexlansoprazole placebo-matching capsule, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsule, orally, once daily for up to 4 weeks.	Total of all reporting groups
Overall Participants	108	107	215
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.1 (12.73)	43.6 (13.24)	44.3 (12.98)
Sex: Female, Male (Count of Participants)
Female	65 60.2%	60 56.1%	125 58.1%
Male	43 39.8%	47 43.9%	90 41.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	108 100%	107 100%	215 100%
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	108 100%	107 100%	215 100%
Body mass index (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	23.935 (3.4352)	23.701 (3.5768)	23.819 (3.5002)
Helicobacter pylori status (Count of Participants)
Positive	41 38%	40 37.4%	81 37.7%
Negative	67 62%	67 62.6%	134 62.3%
Number of days with day and nighttime heartburn between study days -8 to -2 (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	6.1 (1.27)	6.1 (1.06)	6.1 (1.17)
Number of days with nighttime heartburn between study days -8 to -2 (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	5.2 (1.83)	5.3 (1.60)	5.2 (1.71)
Number of days with daytime heartburn between study days -8 to -2 (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	5.6 (1.45)	5.3 (1.61)	5.5 (1.54)
Severity of GERD symptoms: heartburn (Count of Participants)
None	0 0%	0 0%	0 0%
Mild	29 26.9%	33 30.8%	62 28.8%
Moderate	56 51.9%	55 51.4%	111 51.6%
Severe	22 20.4%	17 15.9%	39 18.1%
Very Severe	1 0.9%	2 1.9%	3 1.4%
Severity of GERD symptoms: acid regurgitation (Count of Participants)
None	27 25%	33 30.8%	60 27.9%
Mild	42 38.9%	43 40.2%	85 39.5%
Moderate	27 25%	24 22.4%	51 23.7%
Severe	12 11.1%	6 5.6%	18 8.4%
Very Severe	0 0%	1 0.9%	1 0.5%
Severity of GERD symptoms: dysphagia (Count of Participants)
None	101 93.5%	103 96.3%	204 94.9%
Mild	7 6.5%	4 3.7%	11 5.1%
Moderate	0 0%	0 0%	0 0%
Severe	0 0%	0 0%	0 0%
Very Severe	0 0%	0 0%	0 0%
Severity of GERD symptoms: belching (Count of Participants)
None	59 54.6%	62 57.9%	121 56.3%
Mild	38 35.2%	37 34.6%	75 34.9%
Moderate	9 8.3%	6 5.6%	15 7%
Severe	2 1.9%	2 1.9%	4 1.9%
Very Severe	0 0%	0 0%	0 0%
Severity of GERD symptoms: epigastric pain (Count of Participants)
None	95 88%	88 82.2%	183 85.1%
Mild	11 10.2%	16 15%	27 12.6%
Moderate	2 1.9%	2 1.9%	4 1.9%
Severe	0 0%	1 0.9%	1 0.5%
Very Severe	0 0%	0 0%	0 0%
Number of days with rescue medication use (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	1.7 (2.68)	0.9 (1.48)	1.3 (2.19)

Outcome Measures

1. Primary Outcome

Title	Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment
Description	The percentage of days with neither daytime nor nighttime heartburn was equal to (=) (the days that were heartburn-free during the treatment period) / (total number of days for which either a daytime or nighttime result was marked during treatment period)*100 percent (%).
Time Frame	Up to Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of study drug and had post-baseline (post Day-1) data for the appropriate efficacy variables.

Arm/Group Title	Placebo	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole placebo-matching capsule, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsule, orally, once daily for up to 4 weeks.
Measure Participants	108	107
Median (Full Range) [percentage of days]	32.67	51.72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dexlansoprazole 30 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments
	Method	Wilcoxon rank-sum test
	Comments

2. Secondary Outcome

Title	Percentage of Days Without Nighttime Heartburn During Treatment
Description	The percentage of days without nighttime heartburn was = (the days that were heartburn-free during the treatment period) / (total number of days for which nighttime result was marked during treatment period)*100%.
Time Frame	Up to Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of study drug and had post-baseline (post Day-1) data for the appropriate efficacy variables.

Arm/Group Title	Placebo	Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole placebo-matching capsule, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsule, orally, once daily for up to 4 weeks.
Measure Participants	108	107
Median (Full Range) [percentage of days]	54.67	67.86

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dexlansoprazole 30 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.268
	Comments
	Method	Wilcoxon rank-sum test
	Comments

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 the last dose of double-blind study drug (approximately Week 8).
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	Placebo		Dexlansoprazole 30 mg
Arm/Group Description	Dexlansoprazole placebo-matching capsule, orally, once daily for up to 4 weeks.		Dexlansoprazole 30 mg, capsule, orally, once daily for up to 4 weeks.
All Cause Mortality
	Placebo		Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/108 (0%)		0/107 (0%)
Serious Adverse Events
	Placebo		Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/108 (0%)		1/107 (0.9%)
Injury, poisoning and procedural complications
Animal scratch	0/108 (0%)		1/107 (0.9%)
Other (Not Including Serious) Adverse Events
	Placebo		Dexlansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/108 (13.9%)		9/107 (8.4%)
Infections and infestations
Upper respiratory tract infection	8/108 (7.4%)		5/107 (4.7%)
Nasopharyngitis	7/108 (6.5%)		4/107 (3.7%)

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.