Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Bismuth-Containing Quadruple Therapy With Oral Vonoprazan (TAK-438) 20 mg Compared to Esomeprazole 20 mg Twice Daily in Paticipants With Helicobacter Pylori Infection (NCT NCT04198363)

NCT ID: NCT04198363

Last Updated: 2023-09-07

Results Overview

HP infection status was determined by \^13C Urea Breath Test (\^13C-UBT). The urea breath test is used to detect infection with HP, a bacteria associated with stomach ulcers, by testing individual breath samples in a central laboratory. The percentages are rounded off to report the nearest ten.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

510 participants

Primary outcome timeframe

Week 4 post-treatment

Results posted on

2023-09-07

Participant Flow

Participants took part in the study at 29 investigative sites in China from 30 April 2020 to 25 November 2021.

Helicobacter pylori (HP) positive participants were enrolled and randomized to one of the two treatment groups to either receive quadruple therapy with amoxicillin, clarithromycin, bismuth, and vonoprazan versus quadruple therapy with amoxicillin, clarithromycin, bismuth, and esomeprazole.

Participant milestones

Participant milestones
Measure	Vonoprazan 20 mg Vonoprazan 20 mg, tablets, orally, twice daily (BID) given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.	Esomeprazole 20 mg Esomeprazole 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.
Overall Study STARTED	256	254
Overall Study COMPLETED	254	252
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Vonoprazan 20 mg Vonoprazan 20 mg, tablets, orally, twice daily (BID) given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.	Esomeprazole 20 mg Esomeprazole 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.
Overall Study Adverse Event	1	1
Overall Study Voluntary Withdrawal by Subject	0	1
Overall Study Reason not Specified	1	0

Baseline Characteristics

Number analyzed includes all participants in the FAS who had evaluable data at Baseline, defined as last observation up to Study Day 1.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vonoprazan 20 mg n=256 Participants Vonoprazan 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.	Esomeprazole 20 mg n=254 Participants Esomeprazole 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.	Total n=510 Participants Total of all reporting groups
Age, Continuous	39.5 years STANDARD_DEVIATION 12.29 • n=256 Participants	38.3 years STANDARD_DEVIATION 12.13 • n=254 Participants	38.9 years STANDARD_DEVIATION 12.21 • n=510 Participants
Sex: Female, Male Female	151 Participants n=256 Participants	164 Participants n=254 Participants	315 Participants n=510 Participants
Sex: Female, Male Male	105 Participants n=256 Participants	90 Participants n=254 Participants	195 Participants n=510 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	256 Participants n=256 Participants	254 Participants n=254 Participants	510 Participants n=510 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Race (NIH/OMB) Asian	256 Participants n=256 Participants	254 Participants n=254 Participants	510 Participants n=510 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Race (NIH/OMB) Black or African American	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Race (NIH/OMB) White	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Race (NIH/OMB) More than one race	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=256 Participants	0 Participants n=254 Participants	0 Participants n=510 Participants
Region of Enrollment China	256 Participants n=256 Participants	254 Participants n=254 Participants	510 Participants n=510 Participants
Height	164.9 cm STANDARD_DEVIATION 8.23 • n=256 Participants	164.3 cm STANDARD_DEVIATION 7.70 • n=254 Participants	164.6 cm STANDARD_DEVIATION 7.97 • n=510 Participants
Weight	61.90 kg STANDARD_DEVIATION 10.579 • n=253 Participants • Number analyzed includes all participants in the FAS who had evaluable data at Baseline, defined as last observation up to Study Day 1.	61.15 kg STANDARD_DEVIATION 9.568 • n=249 Participants • Number analyzed includes all participants in the FAS who had evaluable data at Baseline, defined as last observation up to Study Day 1.	61.53 kg STANDARD_DEVIATION 10.087 • n=502 Participants • Number analyzed includes all participants in the FAS who had evaluable data at Baseline, defined as last observation up to Study Day 1.
Body Mass Index (BMI)	22.66 kg/m^2 STANDARD_DEVIATION 2.913 • n=253 Participants • Number analyzed includes all participants in the FAS who had evaluable data at Baseline, defined as last observation up to Study Day 1.	22.61 kg/m^2 STANDARD_DEVIATION 2.735 • n=249 Participants • Number analyzed includes all participants in the FAS who had evaluable data at Baseline, defined as last observation up to Study Day 1.	22.63 kg/m^2 STANDARD_DEVIATION 2.823 • n=502 Participants • Number analyzed includes all participants in the FAS who had evaluable data at Baseline, defined as last observation up to Study Day 1.

PRIMARY outcome

Timeframe: Week 4 post-treatment

Population: FAS included all randomized participants who received at least 1 dose of the study drug. Overall number analyzed are the number of participants who had available HP eradication status determined by \^13C-UBT at Week 4 post-treatment.

Outcome measures

Outcome measures
Measure	Vonoprazan 20 mg n=242 Participants Vonoprazan 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.	Esomeprazole 20 mg n=240 Participants Esomeprazole 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.
Percentage of Helicobacter Pylori Positive (HP+) Participants With Successful HP Eradication at Week 4 Post-Treatment	86.8 percentage of participants	86.7 percentage of participants

Adverse Events

Vonoprazan 20 mg

Serious events: 3 serious events

Other events: 110 other events

Deaths: 0 deaths

Esomeprazole 20 mg

Serious events: 5 serious events

Other events: 91 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vonoprazan 20 mg n=256 participants at risk Vonoprazan 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.	Esomeprazole 20 mg n=254 participants at risk Esomeprazole 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.
Cardiac disorders Arrhythmia supraventricular	0.39% 1/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Chronic gastritis	0.00% 0/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.39% 1/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Infections and infestations Enteritis infectious	0.00% 0/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.39% 1/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.39% 1/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of breast	0.66% 1/151 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/164 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.39% 1/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Cervical dysplasia	0.00% 0/151 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.61% 1/164 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Ovarian cyst ruptured	0.00% 0/151 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.61% 1/164 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.39% 1/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Vonoprazan 20 mg n=256 participants at risk Vonoprazan 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.	Esomeprazole 20 mg n=254 participants at risk Esomeprazole 20 mg, tablets, orally, BID given in combination with bismuth-containing quadruple therapy (amoxicillin 1 g capsules, clarithromycin 500 mg tablets, and bismuth potassium citrate 600 mg capsules) orally, BID for 2 weeks.
Gastrointestinal disorders Faeces discoloured	5.1% 13/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	3.1% 8/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	6.6% 17/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	3.5% 9/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Investigations Protein urine present	7.0% 18/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	5.9% 15/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.
Nervous system disorders Dysgeusia	32.4% 83/256 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.	29.1% 74/254 • From first dose of study drug up to approximately 6 weeks 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. Safety Analysis Set included all participants who received at least 1 dose of study drug.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

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