Trial Outcomes & Findings for Compare D961H 20 mg Bid and 20 mg qd in Patients With Refractory Reflux Esophagitis (Inflammation of Lower Esophagus) (NCT NCT01669811)

Results Overview

Percentage of participants with healing of reflux esophagitis (RE) who were graded "O" (No RE) at Week 8 out of participants who were graded "A" (least severe) to "D" (most severe) at baseline according to Los Angeles classification

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1398 participants

Primary outcome timeframe

8 Weeks

Results posted on

2015-08-27

Participant Flow

First subject enrolled on 25 August 2012. Last subject completed on 30 May 2014.

Out of 1398 enrolled subjects, 287 subjects were randomised and 1111 subjects were not randomised. The reasons of no randomisation were 'Eligibilty criteria not met' (1067 subjects), 'Subject decision' (37 subjects), 'Adverse event' (2 subjects) and other reasons (5 subjects).

Participant milestones

Participant milestones
Measure	D961H 20 mg BID Hard capsule containing 22.3 mg of D961H as enteric coated pellets	D961H 20 mg QD + Placebo Hard capsule unidentifiable to D961H capsule 20 mg
Overall Study STARTED	145	142
Overall Study COMPLETED	142	131
Overall Study NOT COMPLETED	3	11

Reasons for withdrawal

Reasons for withdrawal
Measure	D961H 20 mg BID Hard capsule containing 22.3 mg of D961H as enteric coated pellets	D961H 20 mg QD + Placebo Hard capsule unidentifiable to D961H capsule 20 mg
Overall Study Investigator decision	0	1
Overall Study Withdrawal by Subject	1	2
Overall Study Adverse Event	2	6
Overall Study Eligibility Criteria Not Fulfilled	0	2

Baseline Characteristics

Compare D961H 20 mg Bid and 20 mg qd in Patients With Refractory Reflux Esophagitis (Inflammation of Lower Esophagus)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	D961H 20 mg BID n=145 Participants D961H 20 mg twice Daily	D961H 20 mg QD + Placebo n=140 Participants D961H 20 mg once daily along with placebo	Total n=285 Participants Total of all reporting groups
Age, Continuous	64.7 Years STANDARD_DEVIATION 13.87 • n=5 Participants	61.7 Years STANDARD_DEVIATION 14.72 • n=7 Participants	63.2 Years STANDARD_DEVIATION 14.35 • n=5 Participants
Age, Customized <65	68 Participants n=5 Participants	69 Participants n=7 Participants	137 Participants n=5 Participants
Age, Customized >=65	77 Participants n=5 Participants	71 Participants n=7 Participants	148 Participants n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	70 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	70 Participants n=7 Participants	146 Participants n=5 Participants
Race/Ethnicity, Customized Asian	145 Participants n=5 Participants	140 Participants n=7 Participants	285 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 Weeks

Population: Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product

Percentage of participants with healing of reflux esophagitis (RE) who were graded "O" (No RE) at Week 8 out of participants who were graded "A" (least severe) to "D" (most severe) at baseline according to Los Angeles classification

Outcome measures

Outcome measures
Measure	D961H 20mg Bid n=145 Participants D961H 20mg twice daily	D961H 20mg QD + Placebo n=140 Participants D961H 20mg once daily along with placebo
Percentage of Participants With Healing of RE Who Were Graded "O" at Week 8 Out of Participants Who Were Graded "A" to "D" at Baseline According to Los Angeles Classification	92.4 Percentage of participants Interval 86.9 to 95.7	68.6 Percentage of participants Interval 60.5 to 75.7

SECONDARY outcome

Timeframe: 4 Weeks

Population: Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product

Percentage of participants with healing of reflux esophagitis (RE) who were graded "O" (No RE) at Week 4 out of participants who were graded "A" (least severe) to "D" (most severe) at baseline according to Los Angeles classification

Outcome measures

Outcome measures
Measure	D961H 20mg Bid n=145 Participants D961H 20mg twice daily	D961H 20mg QD + Placebo n=140 Participants D961H 20mg once daily along with placebo
Percentage of Participants With Healing of RE Who Were Graded "O" at Week 4 Out of Participants Who Were Graded "A" to "D" at Baseline According to Los Angeles Classification	81.4 Percentage of participants Interval 74.3 to 86.9	48.6 Percentage of participants Interval 40.4 to 56.8

SECONDARY outcome

Timeframe: 4 Weeks

Population: Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -heartburn at baseline were included.

Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -heartburn at Week 4 (on Day 29) based on the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	D961H 20mg Bid n=90 Participants D961H 20mg twice daily	D961H 20mg QD + Placebo n=81 Participants D961H 20mg once daily along with placebo
Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Heartburn at Week 4	81.1 Percentage of participants Interval 74.3 to 86.9	72.8 Percentage of participants Interval 40.4 to 56.8

SECONDARY outcome

Timeframe: 4 Weeks

Population: Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -acid regurgitation at baseline were included.

Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -acid regurgitation at Week 4 (on Day 29) based on the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	D961H 20mg Bid n=78 Participants D961H 20mg twice daily	D961H 20mg QD + Placebo n=67 Participants D961H 20mg once daily along with placebo
Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Acid Regurgitation at Week 4	73.1 Percentage of participants Interval 74.3 to 86.9	61.2 Percentage of participants Interval 40.4 to 56.8

SECONDARY outcome

Timeframe: 4 Weeks

Population: Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -abdominal pain at baseline were included.

Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -abdominal pain at Week 4 (on Day 29) based on the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	D961H 20mg Bid n=47 Participants D961H 20mg twice daily	D961H 20mg QD + Placebo n=44 Participants D961H 20mg once daily along with placebo
Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Abdominal Pain at Week 4	68.1 Percentage of participants Interval 74.3 to 86.9	59.1 Percentage of participants Interval 40.4 to 56.8

SECONDARY outcome

Timeframe: 4 Weeks

Population: Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -difficulty of swallowing at baseline were included.

Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -difficulty of swallowing at Week 4 (on Day 29) based on the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	D961H 20mg Bid n=28 Participants D961H 20mg twice daily	D961H 20mg QD + Placebo n=27 Participants D961H 20mg once daily along with placebo
Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Difficulty of Swallowing at Week 4	78.6 Percentage of participants Interval 74.3 to 86.9	74.1 Percentage of participants Interval 40.4 to 56.8

SECONDARY outcome

Timeframe: 4 Weeks

Population: Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -sleep disturbance at baseline were included.

Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -sleep disturbance at Week 4 (on Day 29) based on the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	D961H 20mg Bid n=34 Participants D961H 20mg twice daily	D961H 20mg QD + Placebo n=28 Participants D961H 20mg once daily along with placebo
Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Sleep Disturbance at Week 4	91.2 Percentage of participants Interval 74.3 to 86.9	89.3 Percentage of participants Interval 40.4 to 56.8

Adverse Events

D961H 20 mg BID

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

D961H 20 mg QD + Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	D961H 20 mg BID n=145 participants at risk D961H 20 mg twice Daily	D961H 20 mg QD + Placebo n=142 participants at risk D961H 20 mg once daily along with placebo
Gastrointestinal disorders Gastritis	0.00% 0/145	0.70% 1/142 • Number of events 1
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/145	0.70% 1/142 • Number of events 1
Gastrointestinal disorders Pancreatic pseudocyst	0.69% 1/145 • Number of events 1	0.00% 0/142
Infections and infestations Parotid abscess	0.00% 0/145	0.70% 1/142 • Number of events 1

Other adverse events

Other adverse events
Measure	D961H 20 mg BID n=145 participants at risk D961H 20 mg twice Daily	D961H 20 mg QD + Placebo n=142 participants at risk D961H 20 mg once daily along with placebo
Infections and infestations Nasopharyngitis	5.5% 8/145 • Number of events 8	6.3% 9/142 • Number of events 9

Additional Information

Masahiro Nii

Clinical Statistics & Programming Department, Clinical Science Division, R&D, AstraZeneca Japan

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All PIs were prohibited to disclose all information related to this study withiout AZ approval before this study was completed.
Publication restrictions are in place

Restriction type: OTHER