Trial Outcomes & Findings for Comparison of Vonoprazan to Esomeprazole in Participants With Symptomatic GERD Who Responded Partially to a High Dose of Proton Pump Inhibitor (PPI) (NCT NCT02743949)

Last Updated: 2020-02-18

Results Overview

Participants used the Reflux Symptom Questionnaire Electronic Diary (RESQ-eD) every morning upon waking and every evening before going to sleep to document the presence of daytime and nighttime heartburn and regurgitation. The percentage of heartburn-free (HBF) 24-hour periods was calculated for each participant using the following formula: (total 24-hour periods that are heartburn free / total 24-hour periods for which both a daytime and nighttime result is marked) x 100%.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

256 participants

Primary outcome timeframe

4 Weeks

Results posted on

2020-02-18

Participant Flow

Participants took part in the study at 33 investigative sites in Belgium, Bulgaria, Czech Republic, Estonia, Poland and United Kingdom from 14 July 2016 to 12 October 2018.

Participants with a symptomatic gastro-esophageal reflux disease who have a partial response following treatment with a high dose of proton pump inhibitor were enrolled in a 1:1:1 ratio to receive esomeprazole 40 mg, vonoprazan 20 mg, or vonoprazan 40 mg.

Participant milestones

Participant milestones
Measure	Esomeprazole 40 mg Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over-encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.	Vonoprazan 20 mg Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.	Vonoprazan 40 mg Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.
Overall Study STARTED	86	85	85
Overall Study COMPLETED	82	84	82
Overall Study NOT COMPLETED	4	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Esomeprazole 40 mg Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over-encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.	Vonoprazan 20 mg Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.	Vonoprazan 40 mg Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.
Overall Study Adverse Event	0	0	2
Overall Study Significant Protocol Deviation	2	0	1
Overall Study Voluntary Withdrawal	2	1	0

Baseline Characteristics

Data are reported for evaluable participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Esomeprazole 40 mg n=86 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over-encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.	Vonoprazan 20 mg n=85 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.	Vonoprazan 40 mg n=85 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.	Total n=256 Participants Total of all reporting groups
Age, Continuous	53.9 years STANDARD_DEVIATION 13.94 • n=86 Participants	52.0 years STANDARD_DEVIATION 14.67 • n=85 Participants	51.8 years STANDARD_DEVIATION 14.09 • n=85 Participants	52.6 years STANDARD_DEVIATION 14.21 • n=256 Participants
Sex: Female, Male Female	48 Participants n=86 Participants	53 Participants n=85 Participants	51 Participants n=85 Participants	152 Participants n=256 Participants
Sex: Female, Male Male	38 Participants n=86 Participants	32 Participants n=85 Participants	34 Participants n=85 Participants	104 Participants n=256 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=86 Participants	0 Participants n=85 Participants	0 Participants n=85 Participants	0 Participants n=256 Participants
Race (NIH/OMB) Asian	0 Participants n=86 Participants	0 Participants n=85 Participants	1 Participants n=85 Participants	1 Participants n=256 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=86 Participants	0 Participants n=85 Participants	1 Participants n=85 Participants	1 Participants n=256 Participants
Race (NIH/OMB) Black or African American	0 Participants n=86 Participants	1 Participants n=85 Participants	0 Participants n=85 Participants	1 Participants n=256 Participants
Race (NIH/OMB) White	86 Participants n=86 Participants	84 Participants n=85 Participants	83 Participants n=85 Participants	253 Participants n=256 Participants
Race (NIH/OMB) More than one race	0 Participants n=86 Participants	0 Participants n=85 Participants	0 Participants n=85 Participants	0 Participants n=256 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=86 Participants	0 Participants n=85 Participants	0 Participants n=85 Participants	0 Participants n=256 Participants
Region of Enrollment Belgium	0 Participants n=86 Participants	1 Participants n=85 Participants	0 Participants n=85 Participants	1 Participants n=256 Participants
Region of Enrollment Bulgaria	61 Participants n=86 Participants	55 Participants n=85 Participants	61 Participants n=85 Participants	177 Participants n=256 Participants
Region of Enrollment Czech Republic	14 Participants n=86 Participants	16 Participants n=85 Participants	10 Participants n=85 Participants	40 Participants n=256 Participants
Region of Enrollment Estonia	2 Participants n=86 Participants	5 Participants n=85 Participants	4 Participants n=85 Participants	11 Participants n=256 Participants
Region of Enrollment Poland	8 Participants n=86 Participants	7 Participants n=85 Participants	7 Participants n=85 Participants	22 Participants n=256 Participants
Region of Enrollment United Kingdom	1 Participants n=86 Participants	1 Participants n=85 Participants	3 Participants n=85 Participants	5 Participants n=256 Participants
Smoking Status Participant has never smoked	50 Participants n=86 Participants	53 Participants n=85 Participants	53 Participants n=85 Participants	156 Participants n=256 Participants
Smoking Status Participant is a current smoker	21 Participants n=86 Participants	23 Participants n=85 Participants	22 Participants n=85 Participants	66 Participants n=256 Participants
Smoking Status Participant is an ex-smoker	15 Participants n=86 Participants	9 Participants n=85 Participants	10 Participants n=85 Participants	34 Participants n=256 Participants
Alcohol Classification Participant has never drunk	57 Participants n=86 Participants	49 Participants n=85 Participants	54 Participants n=85 Participants	160 Participants n=256 Participants
Alcohol Classification Participant is a current drinker	27 Participants n=86 Participants	33 Participants n=85 Participants	30 Participants n=85 Participants	90 Participants n=256 Participants
Alcohol Classification Participant is an ex-drinker	2 Participants n=86 Participants	3 Participants n=85 Participants	1 Participants n=85 Participants	6 Participants n=256 Participants
Alcohol Use Less than 21 units of alcohol per week	27 Participants n=86 Participants	33 Participants n=85 Participants	30 Participants n=85 Participants	90 Participants n=256 Participants
Alcohol Use Missing	59 Participants n=86 Participants	52 Participants n=85 Participants	55 Participants n=85 Participants	166 Participants n=256 Participants
Caffeine Consumption Yes	60 Participants n=86 Participants	67 Participants n=85 Participants	68 Participants n=85 Participants	195 Participants n=256 Participants
Caffeine Consumption No	26 Participants n=86 Participants	18 Participants n=85 Participants	17 Participants n=85 Participants	61 Participants n=256 Participants
Height	169.9 centimeters (cm) STANDARD_DEVIATION 9.17 • n=86 Participants	168.5 centimeters (cm) STANDARD_DEVIATION 9.07 • n=85 Participants	168.1 centimeters (cm) STANDARD_DEVIATION 7.81 • n=85 Participants	168.9 centimeters (cm) STANDARD_DEVIATION 8.71 • n=256 Participants
Weight	78.78 kilograms (kg) STANDARD_DEVIATION 17.003 • n=86 Participants	77.46 kilograms (kg) STANDARD_DEVIATION 16.353 • n=85 Participants	75.81 kilograms (kg) STANDARD_DEVIATION 16.126 • n=85 Participants	77.36 kilograms (kg) STANDARD_DEVIATION 16.481 • n=256 Participants
Body Mass Index (BMI)	27.13 kg per square meter (kg/m^2) STANDARD_DEVIATION 4.611 • n=86 Participants	27.21 kg per square meter (kg/m^2) STANDARD_DEVIATION 4.854 • n=85 Participants	26.76 kg per square meter (kg/m^2) STANDARD_DEVIATION 5.076 • n=85 Participants	27.03 kg per square meter (kg/m^2) STANDARD_DEVIATION 4.835 • n=256 Participants
Hospital Anxiety and Depression Scale (HADS) Anxiety Total	6.5 score on scale STANDARD_DEVIATION 3.81 • n=85 Participants • Data are reported for evaluable participants.	6.2 score on scale STANDARD_DEVIATION 3.38 • n=84 Participants • Data are reported for evaluable participants.	7.0 score on scale STANDARD_DEVIATION 3.78 • n=85 Participants • Data are reported for evaluable participants.	6.6 score on scale STANDARD_DEVIATION 3.67 • n=254 Participants • Data are reported for evaluable participants.
Depression Total	5.9 score on scale STANDARD_DEVIATION 3.62 • n=85 Participants • Data are reported for evaluable participants.	6.0 score on scale STANDARD_DEVIATION 3.50 • n=84 Participants • Data are reported for evaluable participants.	6.2 score on scale STANDARD_DEVIATION 3.99 • n=85 Participants • Data are reported for evaluable participants.	6.0 score on scale STANDARD_DEVIATION 3.70 • n=254 Participants • Data are reported for evaluable participants.
Is Erosive Esophagitis Present? Yes	30 Participants n=86 Participants	28 Participants n=85 Participants	17 Participants n=85 Participants	75 Participants n=256 Participants
Is Erosive Esophagitis Present? No	56 Participants n=86 Participants	57 Participants n=85 Participants	68 Participants n=85 Participants	181 Participants n=256 Participants
If Yes, Grade of Erosive Esophagitis Grade 0	0 Participants n=30 Participants • Participants with erosive esophagitis were graded.	1 Participants n=28 Participants • Participants with erosive esophagitis were graded.	1 Participants n=17 Participants • Participants with erosive esophagitis were graded.	2 Participants n=75 Participants • Participants with erosive esophagitis were graded.
If Yes, Grade of Erosive Esophagitis Grade A	30 Participants n=30 Participants • Participants with erosive esophagitis were graded.	27 Participants n=28 Participants • Participants with erosive esophagitis were graded.	16 Participants n=17 Participants • Participants with erosive esophagitis were graded.	73 Participants n=75 Participants • Participants with erosive esophagitis were graded.
Did the Endoscopist Visualize Findings Suggestive of Eosinophilic Esophagitis? No	86 Participants n=86 Participants	85 Participants n=85 Participants	85 Participants n=85 Participants	256 Participants n=256 Participants
H Pylori Status Positive	8 Participants n=86 Participants	13 Participants n=85 Participants	8 Participants n=85 Participants	29 Participants n=256 Participants
H Pylori Status Negative	78 Participants n=86 Participants	72 Participants n=85 Participants	76 Participants n=85 Participants	226 Participants n=256 Participants

PRIMARY outcome

Timeframe: 4 Weeks

Population: The full analysis set (FAS) included all participants randomized to a double-blind study medication. Data are reported for evaluable participants.

Outcome measures

Outcome measures
Measure	Esomeprazole 40 mg n=85 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over-encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.	Vonoprazan 20 mg n=85 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.	Vonoprazan 40 mg n=85 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.
Percentage of Heartburn-Free 24-Hour Periods (Day and Night) During 4 Weeks of Treatment	36.54 percentage of HBF 24-hour periods Standard Deviation 35.570	36.69 percentage of HBF 24-hour periods Standard Deviation 33.420	38.43 percentage of HBF 24-hour periods Standard Deviation 34.793

SECONDARY outcome

Timeframe: 4 Weeks

Population: The full analysis set (FAS) included all participants randomized to a double-blind study medication.

≥1 sustained resolution of heartburn is defined as ≥7 consecutive days without both daytime and nighttime heartburn anytime during the 4-week treatment period. Daytime and nighttime heartburn were documented by all participants using the Reflux Symptom Questionnaire Electronic Diary (RESQ-eD).

Outcome measures

Outcome measures
Measure	Esomeprazole 40 mg n=86 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over-encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.	Vonoprazan 20 mg n=85 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.	Vonoprazan 40 mg n=85 Participants Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.
Percentage of Participants With ≥1 Sustained Resolution of Heartburn During the 4-Week Treatment Period	32.6 percentage of participants	30.6 percentage of participants	31.8 percentage of participants

Adverse Events

Esomeprazole 40 mg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Vonoprazan 20 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vonoprazan 40 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Esomeprazole 40 mg n=86 participants at risk Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over-encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.	Vonoprazan 20 mg n=85 participants at risk Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.	Vonoprazan 40 mg n=85 participants at risk Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.
Nervous system disorders Ischaemic stroke	1.2% 1/86 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	0.00% 0/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	0.00% 0/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.

Other adverse events

Other adverse events
Measure	Esomeprazole 40 mg n=86 participants at risk Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over-encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.	Vonoprazan 20 mg n=85 participants at risk Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.	Vonoprazan 40 mg n=85 participants at risk Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.
Endocrine disorders Hypothyroidism	0.00% 0/86 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	0.00% 0/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	3.5% 3/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.
Gastrointestinal disorders Flatulence	1.2% 1/86 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	0.00% 0/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	2.4% 2/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.
Infections and infestations Urinary tract infection	0.00% 0/86 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	0.00% 0/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.	2.4% 2/85 • Up to 5 weeks An adverse event (AE) is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. Reported AEs are treatment-emergent adverse events (TEAEs). A TEAE is defined as any adverse event that occurred after the first dose of study drug during the double-blind period and up to one week after completion or withdrawal from the study.

Additional Information

Medical Director

Takeda

Phone: 877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER