Trial Outcomes & Findings for Phase 3 Study to Evaluate the Acid-Inhibitory Effect of Multiple Oral Doses of Vonoprazan (TAK-438) (NCT NCT02037477)
NCT ID: NCT02037477
Last Updated: 2016-10-17
Results Overview
Intragastric pH was measured continuously for 24 hours (hr) by pH monitor. pH holding time ratio (HTR) is the percentage of time a pH is maintained at a particular level. For example, pH 4 HTR is the percentage of time the pH = 4.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
20 participants
Primary outcome timeframe
At baseline (Day -2 to Day -1), administration period (Days 1 to Day 2 and Days 7 to Day 8)
Results posted on
2016-10-17
Participant Flow
Participants took part in the study at 1 investigative site in Japan from 3 February 2014 to 27 March 2014.
A total of 56 participants signed the informed consent form. 20 participants were enrolled and received the study drug. The primary reason for ineligibility to receive the study drug was "did not meet entrance criteria" for 16 subjects. Nineteen subjects completed the study, while 1 subject withdrew due to a "pretreatment event/AE."
Participant milestones
| Measure |
Sequence A (Cohort 1): Vonoprazan + Esomeprazole
Vonoprazan (TAK-438) 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then esomeprazole 20 mg, orally, once daily for 7 days.
|
Sequence B (Cohort 1): Esomeprazole + Vonoprazan
Esomeprazole 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then vonoprazan 20 mg, orally, once daily for 7 days.
|
Sequence C (Cohort 2): Vonoprazan + Rabeprazole Sodium
Vonoprazan 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
Sequence D (Cohort 2): Rabeprazole Sodium + Vonoprazan
Rabeprazole sodium 10 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then vonoprazan 20 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
5
|
5
|
5
|
5
|
|
Treatment Period 1
COMPLETED
|
5
|
5
|
4
|
5
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Treatment Period 2
STARTED
|
5
|
5
|
4
|
5
|
|
Treatment Period 2
COMPLETED
|
5
|
5
|
4
|
5
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence A (Cohort 1): Vonoprazan + Esomeprazole
Vonoprazan (TAK-438) 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then esomeprazole 20 mg, orally, once daily for 7 days.
|
Sequence B (Cohort 1): Esomeprazole + Vonoprazan
Esomeprazole 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then vonoprazan 20 mg, orally, once daily for 7 days.
|
Sequence C (Cohort 2): Vonoprazan + Rabeprazole Sodium
Vonoprazan 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
Sequence D (Cohort 2): Rabeprazole Sodium + Vonoprazan
Rabeprazole sodium 10 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then vonoprazan 20 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Treatment Period 1
Pre-treatment Event/Adverse Event
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Phase 3 Study to Evaluate the Acid-Inhibitory Effect of Multiple Oral Doses of Vonoprazan (TAK-438)
Baseline characteristics by cohort
| Measure |
Sequence A (Cohort 1): Vonoprazan + Esomeprazole
n=5 Participants
Vonoprazan (TAK-438) 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then esomeprazole 20 mg, orally, once daily for 7 days.
|
Sequence B (Cohort 1): Esomeprazole + Vonoprazan
n=5 Participants
Esomeprazole 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then vonoprazan 20 mg, orally, once daily for 7 days.
|
Sequence C (Cohort 2): Vonoprazan + Rabeprazole Sodium
n=5 Participants
Vonoprazan 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
Sequence D (Cohort 2): Rabeprazole Sodium + Vonoprazan
n=5 Participants
Rabeprazole sodium 10 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days and then vonoprazan 20 mg, orally, once daily for 7 days.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
34.0 years
STANDARD_DEVIATION 6.93 • n=5 Participants
|
23.8 years
STANDARD_DEVIATION 5.17 • n=7 Participants
|
22.2 years
STANDARD_DEVIATION 2.95 • n=5 Participants
|
25.2 years
STANDARD_DEVIATION 2.95 • n=4 Participants
|
25.2 years
STANDARD_DEVIATION 5.31 • n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
Region of Enrollment
Japan
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
5 participants
n=4 Participants
|
20 participants
n=21 Participants
|
|
Height
|
172.0 cm
STANDARD_DEVIATION 7.75 • n=5 Participants
|
173.0 cm
STANDARD_DEVIATION 6.52 • n=7 Participants
|
172.8 cm
STANDARD_DEVIATION 6.76 • n=5 Participants
|
169.4 cm
STANDARD_DEVIATION 4.88 • n=4 Participants
|
171.8 cm
STANDARD_DEVIATION 6.48 • n=21 Participants
|
|
Weight
|
64.10 kg
STANDARD_DEVIATION 8.930 • n=5 Participants
|
64.10 kg
STANDARD_DEVIATION 9.813 • n=7 Participants
|
62.68 kg
STANDARD_DEVIATION 5.008 • n=5 Participants
|
58.34 kg
STANDARD_DEVIATION 5.227 • n=4 Participants
|
62.31 kg
STANDARD_DEVIATION 7.245 • n=21 Participants
|
|
Body Mass Index (BMI)
|
21.56 kg/m^2
STANDARD_DEVIATION 1.674 • n=5 Participants
|
21.32 kg/m^2
STANDARD_DEVIATION 1.844 • n=7 Participants
|
20.96 kg/m^2
STANDARD_DEVIATION 0.808 • n=5 Participants
|
20.34 kg/m^2
STANDARD_DEVIATION 1.222 • n=4 Participants
|
21.05 kg/m^2
STANDARD_DEVIATION 1.387 • n=21 Participants
|
|
CPY2C19 Genotype Test (N)
Homo Extensive Metabolizer (EM)
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
2 participants
n=4 Participants
|
10 participants
n=21 Participants
|
|
CPY2C19 Genotype Test (N)
Hetero EM
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
10 participants
n=21 Participants
|
|
CPY2C19 Genotype Test (N)
Poor Metabolizer (PM)
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: At baseline (Day -2 to Day -1), administration period (Days 1 to Day 2 and Days 7 to Day 8)Population: Pharmacodynamic (PD) Analysis Set - Participants receiving study medication who completed protocol procedures without serious violation of the protocol were eligible for PD analysis. All 10 subjects from Cohort 1 were included. Three subjects in Cohort 2 were excluded from the PD analysis set, which therefore consisted of 7 subjects.
Intragastric pH was measured continuously for 24 hours (hr) by pH monitor. pH holding time ratio (HTR) is the percentage of time a pH is maintained at a particular level. For example, pH 4 HTR is the percentage of time the pH = 4.
Outcome measures
| Measure |
Cohort 1 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 1 - Esomeprazole 20 mg
n=10 Participants
Esomeprazole 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Vonoprazan 20 mg
n=7 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Rabeprazole Sodium 10 mg
n=7 Participants
Rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Intragastric pH Time Course Over 24 Hours
0-24 hr pH 4 HTR (%)-Baseline
|
10.63 percentage of time
Standard Deviation 7.391
|
10.63 percentage of time
Standard Deviation 7.391
|
8.90 percentage of time
Standard Deviation 6.472
|
8.90 percentage of time
Standard Deviation 6.472
|
|
Intragastric pH Time Course Over 24 Hours
0-24 hr pH 4 HTR (%)-Day 1
|
71.37 percentage of time
Standard Deviation 17.030
|
23.92 percentage of time
Standard Deviation 16.896
|
84.16 percentage of time
Standard Deviation 12.383
|
26.29 percentage of time
Standard Deviation 13.381
|
|
Intragastric pH Time Course Over 24 Hours
0-24 hr pH 4 HTR (%)-Day 7
|
85.82 percentage of time
Standard Deviation 14.748
|
61.21 percentage of time
Standard Deviation 17.140
|
93.79 percentage of time
Standard Deviation 7.310
|
65.09 percentage of time
Standard Deviation 14.159
|
|
Intragastric pH Time Course Over 24 Hours
0-12 hr pH 4 HTR (%)-Baseline
|
12.98 percentage of time
Standard Deviation 11.139
|
12.98 percentage of time
Standard Deviation 11.139
|
8.01 percentage of time
Standard Deviation 5.730
|
8.01 percentage of time
Standard Deviation 5.730
|
|
Intragastric pH Time Course Over 24 Hours
0-12 hr pH 4 HTR (%)-Day 1
|
74.83 percentage of time
Standard Deviation 9.681
|
34.89 percentage of time
Standard Deviation 24.645
|
84.03 percentage of time
Standard Deviation 7.810
|
37.26 percentage of time
Standard Deviation 20.384
|
|
Intragastric pH Time Course Over 24 Hours
0-12 hr pH 4 HTR (%)-Day 7
|
96.45 percentage of time
Standard Deviation 4.402
|
77.62 percentage of time
Standard Deviation 17.302
|
98.83 percentage of time
Standard Deviation 2.968
|
76.06 percentage of time
Standard Deviation 9.591
|
|
Intragastric pH Time Course Over 24 Hours
12-24 hr pH 4 HTR (%)-Baseline
|
8.18 percentage of time
Standard Deviation 13.735
|
8.18 percentage of time
Standard Deviation 13.735
|
9.77 percentage of time
Standard Deviation 14.096
|
9.77 percentage of time
Standard Deviation 14.096
|
|
Intragastric pH Time Course Over 24 Hours
12-24 hr pH 4 HTR (%)-Day 1
|
67.86 percentage of time
Standard Deviation 28.345
|
12.94 percentage of time
Standard Deviation 10.876
|
84.34 percentage of time
Standard Deviation 20.254
|
15.34 percentage of time
Standard Deviation 13.317
|
|
Intragastric pH Time Course Over 24 Hours
12-24 hr pH 4 HTR (%)-Day 7
|
75.21 percentage of time
Standard Deviation 26.398
|
44.81 percentage of time
Standard Deviation 17.338
|
88.77 percentage of time
Standard Deviation 14.369
|
54.13 percentage of time
Standard Deviation 25.275
|
SECONDARY outcome
Timeframe: 31 daysPopulation: Safety analysis set - All participants who received at least 1 dose of study drug.
The frequency of adverse events by type, seriousness, time to onset. Adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug to the last dose of study drug.
Outcome measures
| Measure |
Cohort 1 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 1 - Esomeprazole 20 mg
n=10 Participants
Esomeprazole 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Rabeprazole Sodium 10 mg
n=10 Participants
Rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Frequency of Adverse Events
Treatment Emergent Adverse Events
|
0 participants
|
0 participants
|
3 participants
|
1 participants
|
|
Frequency of Adverse Events
Related
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Frequency of Adverse Events
Not Related
|
0 participants
|
0 participants
|
2 participants
|
1 participants
|
|
Frequency of Adverse Events
Mild
|
0 participants
|
0 participants
|
2 participants
|
1 participants
|
|
Frequency of Adverse Events
Moderate
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Frequency of Adverse Events
Severe
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Frequency of Adverse Events
Leading to Study Drug Discontinuation
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: At screening, baseline (Day -3, Day -2, Day -1), administration period (Days 1, Day 2, Day 7, Day 8), and post-test (Day 28)Population: Safety analysis set - All participants who received at least 1 dose of study drug.
Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Outcome measures
| Measure |
Cohort 1 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 1 - Esomeprazole 20 mg
n=10 Participants
Esomeprazole 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Rabeprazole Sodium 10 mg
n=10 Participants
Rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Changes From Baseline in Vital Signs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: At Screening, baseline (Day -3), administration period (Day 8), and post-test (Day 28)Population: Safety analysis set - All participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Cohort 1 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 1 - Esomeprazole 20 mg
n=10 Participants
Esomeprazole 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Rabeprazole Sodium 10 mg
n=10 Participants
Rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal 12-lead Electrocardiogram (at Rest) Findings
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: At Screening, baseline (Day -3), administration period (Day 1, Day 8), and post-test (Day 28)Population: Safety analysis set - All participants who received at least 1 dose of study drug.
The number of participants with markedly abnormal laboratory values for Chemistry, Hematology and Urinalysis during the study is reported.
Outcome measures
| Measure |
Cohort 1 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 1 - Esomeprazole 20 mg
n=10 Participants
Esomeprazole 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Vonoprazan 20 mg
n=10 Participants
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Rabeprazole Sodium 10 mg
n=10 Participants
Rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Number of Participants With Markedly Abnormal Laboratory Values
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Cohort 1 - Vonoprazan 20 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 1 - Esomeprazole 20 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2 - Vonoprazan 20 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 2 - Rabeprazole Sodium 10 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1 - Vonoprazan 20 mg
n=10 participants at risk
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 1 - Esomeprazole 20 mg
n=10 participants at risk
Esomeprazole 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Vonoprazan 20 mg
n=10 participants at risk
Vonoprazan 20 mg, orally, once daily for 7 days.
|
Cohort 2 - Rabeprazole Sodium 10 mg
n=10 participants at risk
Rabeprazole sodium 10 mg, orally, once daily for 7 days.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
10.0%
1/10 • 31 Days
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.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
10.0%
1/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
|
General disorders
Pyrexia
|
0.00%
0/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
10.0%
1/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
10.0%
1/10 • 31 Days
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.
|
0.00%
0/10 • 31 Days
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.
|
Additional Information
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