Trial Outcomes & Findings for Efficacy and Safety of Dexlansoprazole MR and Lansoprazole on Healing of Erosive Esophagitis (NCT NCT00251693)

Last Updated: 2012-02-03

Results Overview

Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A (greater than or equal to 1 mucosal break and less than 5 mm). If it doesn't meet the A criterion, it's counted as healed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2038 participants

Primary outcome timeframe

8 Weeks

Results posted on

2012-02-03

Participant Flow

Subjects were enrolled at 95 sites in the United States (US) and 55 ex-US sites from 02 December 2005 to 30 January 2007.

Subjects recorded day and nighttime heartburn symptoms and rescue medications for a screening period of up to 21 days. Subjects with endoscopically-proven erosive esophagitis (EE) at screening were enrolled in Dexlansoprazole Modified Release (MR) or Lansoprazole once daily (QD) treatment group.

Participant milestones

Participant milestones
Measure	Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Overall Study STARTED	680	668	690
Overall Study COMPLETED	629	624	644
Overall Study NOT COMPLETED	51	44	46

Reasons for withdrawal

Reasons for withdrawal
Measure	Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Overall Study Adverse Event	17	9	9
Overall Study Protocol Violation	2	0	2
Overall Study Lost to Follow-up	12	7	8
Overall Study Withdrawal by Subject	11	17	14
Overall Study Lack of Efficacy	0	1	0
Overall Study Inclusion/exclusion criteria not met	5	3	8
Overall Study Noncompliant	0	0	2
Overall Study Possible Barrett's esophagus	3	5	2
Overall Study Subject request/subject unavailable	1	2	0
Overall Study Abnormal laboratory findings	0	0	1

Baseline Characteristics

Efficacy and Safety of Dexlansoprazole MR and Lansoprazole on Healing of Erosive Esophagitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dexlansoprazole MR 60 mg QD n=680 Participants Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=668 Participants Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=690 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.	Total n=2038 Participants Total of all reporting groups
Age, Customized <45 Years	269 participants n=5 Participants	276 participants n=7 Participants	288 participants n=5 Participants	833 participants n=4 Participants
Age, Customized 45 Years to <65 Years	349 participants n=5 Participants	328 participants n=7 Participants	332 participants n=5 Participants	1009 participants n=4 Participants
Age, Customized >=65 Years	62 participants n=5 Participants	64 participants n=7 Participants	70 participants n=5 Participants	196 participants n=4 Participants
Age Continuous	47.8 years STANDARD_DEVIATION 13.71 • n=5 Participants	47.3 years STANDARD_DEVIATION 13.93 • n=7 Participants	47.3 years STANDARD_DEVIATION 13.74 • n=5 Participants	47.5 years STANDARD_DEVIATION 13.79 • n=4 Participants
Sex: Female, Male Female	300 Participants n=5 Participants	302 Participants n=7 Participants	325 Participants n=5 Participants	927 Participants n=4 Participants
Sex: Female, Male Male	380 Participants n=5 Participants	366 Participants n=7 Participants	365 Participants n=5 Participants	1111 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	60 Participants n=5 Participants	52 Participants n=7 Participants	54 Participants n=5 Participants	166 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	620 Participants n=5 Participants	616 Participants n=7 Participants	636 Participants n=5 Participants	1872 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) Asian	27 Participants n=5 Participants	33 Participants n=7 Participants	33 Participants n=5 Participants	93 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	32 Participants n=5 Participants	33 Participants n=7 Participants	27 Participants n=5 Participants	92 Participants n=4 Participants
Race (NIH/OMB) White	602 Participants n=5 Participants	580 Participants n=7 Participants	601 Participants n=5 Participants	1783 Participants n=4 Participants
Race (NIH/OMB) More than one race	10 Participants n=5 Participants	15 Participants n=7 Participants	17 Participants n=5 Participants	42 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Los Angeles (LA) Classification Grade for Erosive Esophagitis (EE) A: ≥1 mucosal break <5mm	236 Paricipants n=5 Participants	242 Paricipants n=7 Participants	231 Paricipants n=5 Participants	709 Paricipants n=4 Participants
Los Angeles (LA) Classification Grade for Erosive Esophagitis (EE) B: ≥1 mucosal break ≥5mm	247 Paricipants n=5 Participants	233 Paricipants n=7 Participants	248 Paricipants n=5 Participants	728 Paricipants n=4 Participants
Los Angeles (LA) Classification Grade for Erosive Esophagitis (EE) C: ≥1 mucosal break and <75% of the circumference	163 Paricipants n=5 Participants	148 Paricipants n=7 Participants	170 Paricipants n=5 Participants	481 Paricipants n=4 Participants
Los Angeles (LA) Classification Grade for Erosive Esophagitis (EE) D: ≥1 mucosal break and ≥75% of the circumference	33 Paricipants n=5 Participants	45 Paricipants n=7 Participants	40 Paricipants n=5 Participants	118 Paricipants n=4 Participants
Los Angeles (LA) Classification Grade for Erosive Esophagitis (EE) Not Applicable	1 Paricipants n=5 Participants	0 Paricipants n=7 Participants	1 Paricipants n=5 Participants	2 Paricipants n=4 Participants

PRIMARY outcome

Timeframe: 8 Weeks

Population: Crude rate analyses were performed on the ITT subjects who had at least 1 post-baseline endoscopy assessment performed within 7 days of the last day of study drug.

Outcome measures

Outcome measures
Measure	Dexlansoprazole MR 60 mg QD n=639 Participants Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=634 Participants Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=656 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Percentage of Subjects With Complete Healing of Erosive Esophagitis (EE) by Week 8 as Assessed by Endoscopy - Crude Rate Analysis.	85.3 Percentage of subjects Interval 82.3 to 87.9	85.8 Percentage of subjects Interval 82.8 to 88.4	79.0 Percentage of subjects Interval 75.6 to 82.0

PRIMARY outcome

Timeframe: 8 weeks

Population: In addition to the ITT subjects who had at least 1 post-baseline endoscopy, Life Table Method included the ITT subjects without any post-baseline endoscopy within 7 days of the last day of study drug as censored.

Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.

Outcome measures

Outcome measures
Measure	Dexlansoprazole MR 60 mg QD n=673 Participants Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=665 Participants Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=684 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method.	92.3 Percentage of subjects Interval 90.0 to 94.7	92.2 Percentage of subjects Interval 89.8 to 94.6	86.1 Percentage of subjects Interval 83.0 to 89.2

SECONDARY outcome

Timeframe: 8 Weeks

Population: Crude rate analyses were performed on the ITT subjects who had at least 1 post-baseline endoscopy assessment performed within 7 days of the last day of study drug.

Percentage of subjects with baseline EE grade C or D combined who have complete healing of erosive esophagitis as assessed by endoscopy for Change in LA Esophagitis Classification Grades C and D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.

Outcome measures

Outcome measures
Measure	Dexlansoprazole MR 60 mg QD n=182 Participants Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=185 Participants Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=200 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Percentage of Subjects With Baseline Erosive Esophagitis Grade C or D Combined Who Have Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Crude Rate Analysis.	79.7 percentage of subjects Interval 73.1 to 85.3	74.1 percentage of subjects Interval 67.1 to 80.2	65.0 percentage of subjects Interval 58.0 to 71.6

SECONDARY outcome

Timeframe: 8 Weeks

Percentage of subjects with baseline EE grade C or D combined who have complete healing of EE as assessed by endoscopy for Change in LA Esophagitis Classification Grades C and D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.

Outcome measures

Outcome measures
Measure	Dexlansoprazole MR 60 mg QD n=191 Participants Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=191 Participants Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=208 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Percentage of Subjects With Baseline Erosive Esophagitis Grade C or D Combined Who Have Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method.	88.9 percentage of subjects Interval 83.7 to 94.2	83.8 percentage of subjects Interval 77.4 to 90.1	74.5 percentage of subjects Interval 67.3 to 81.6

SECONDARY outcome

Timeframe: 4 Weeks

Population: Crude rate analyses were performed on the ITT subjects who had at least 1 post-baseline endoscopy assessment performed within 7 days of the last day of study drug.

Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.

Outcome measures

Outcome measures
Measure	Dexlansoprazole MR 60 mg QD n=639 Participants Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=634 Participants Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=656 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Crude Rate Analyses.	66.2 Percentage of subjects Interval 62.4 to 69.9	68.8 Percentage of subjects Interval 65.0 to 72.4	64.8 Percentage of subjects Interval 61.0 to 68.4

SECONDARY outcome

Timeframe: 4 Weeks

Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.

Outcome measures

Outcome measures
Measure	Dexlansoprazole MR 60 mg QD n=673 Participants Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=665 Participants Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=684 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Life Table Method.	77.0 Percentage of subjects Interval 73.5 to 80.5	78.8 Percentage of subjects Interval 75.4 to 82.2	76.5 Percentage of subjects Interval 73.0 to 80.0

Adverse Events

Dexlansoprazole MR 60 mg QD

Serious events: 5 serious events

Other events: 63 other events

Deaths: 0 deaths

Dexlansoprazole MR 90 mg QD

Serious events: 2 serious events

Other events: 53 other events

Deaths: 0 deaths

Lansoprazole 30 mg QD

Serious events: 6 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dexlansoprazole MR 60 mg QD n=680 participants at risk Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=668 participants at risk Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=690 participants at risk Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Cardiac disorders Coronary Artery Disorders not elsewhere classified (NEC)	0.15% 1/680	0.00% 0/668	0.00% 0/690
Gastrointestinal disorders Duodenal and Small Intestinal Stenosis and Obstruction	0.00% 0/680	0.00% 0/668	0.14% 1/690
Gastrointestinal disorders Gastrointestinal (GI) Atonic and Hypomotility Disorders NEC	0.15% 1/680	0.00% 0/668	0.00% 0/690
Gastrointestinal disorders Gastrointestinal Inflammatory Disorders NEC	0.00% 0/680	0.15% 1/668	0.00% 0/690
Gastrointestinal disorders Haemorrhoids and GI Varices (Excluding [Excl] Oesophageal)	0.00% 0/680	0.15% 1/668	0.00% 0/690
Gastrointestinal disorders Intestinal Ulcers and Perforation NEC	0.15% 1/680	0.00% 0/668	0.00% 0/690
Gastrointestinal disorders Peritoneal and Retroperitoneal Disorders	0.15% 1/680	0.00% 0/668	0.00% 0/690
General disorders Pain and Discomfort NEC	0.15% 1/680	0.00% 0/668	0.00% 0/690
Hepatobiliary disorders Cholecystitis and Cholelithiasis	0.00% 0/680	0.00% 0/668	0.14% 1/690
Infections and infestations Infections NEC	0.15% 1/680	0.00% 0/668	0.00% 0/690
Infections and infestations Lower Respiratory Tract and Lung Infections	0.15% 1/680	0.00% 0/668	0.00% 0/690
Infections and infestations Sepsis, Bacteraemia, Viraemia and Fungaemia NEC	0.15% 1/680	0.00% 0/668	0.00% 0/690
Infections and infestations Streptococcal Infections	0.00% 0/680	0.00% 0/668	0.14% 1/690
Injury, poisoning and procedural complications Non-site Specfic Procedural Complications	0.00% 0/680	0.00% 0/668	0.14% 1/690
Metabolism and nutrition disorders Potassium Imbalance	0.15% 1/680	0.00% 0/668	0.00% 0/690
Musculoskeletal and connective tissue disorders Soft Tissue Disorders NEC	0.15% 1/680	0.00% 0/668	0.00% 0/690
Nervous system disorders Acute Polyneuropathies	0.15% 1/680	0.00% 0/668	0.00% 0/690
Nervous system disorders Transient Cerebrovascular (CV) Events	0.15% 1/680	0.00% 0/668	0.00% 0/690
Nervous system disorders Paralysis and Paresis (Excl Cranial Nerve)	0.00% 0/680	0.00% 0/668	0.14% 1/690
Nervous system disorders Central Nervous System Hemorrhages and CV accidents	0.00% 0/680	0.00% 0/668	0.14% 1/690
Psychiatric disorders Bipolar Disorders	0.00% 0/680	0.00% 0/668	0.14% 1/690
Respiratory, thoracic and mediastinal disorders Respiratory Failures (Excl Neonatal)	0.15% 1/680	0.00% 0/668	0.00% 0/690

Other adverse events

Other adverse events
Measure	Dexlansoprazole MR 60 mg QD n=680 participants at risk Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks.	Dexlansoprazole MR 90 mg QD n=668 participants at risk Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg QD n=690 participants at risk Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Gastrointestinal disorders Diarrhoea (Excl Infective)	4.0% 27/680	3.6% 24/668	3.0% 21/690
Gastrointestinal disorders Gastrointestinal and Abdominal Pains (Excl Oral and Throat)	2.5% 17/680	3.6% 24/668	2.5% 17/690
Infections and infestations Upper Respiratory Tract Infections	3.5% 24/680	2.5% 17/668	2.5% 17/690

Additional Information

Sr. VP Clinical Sciences

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER