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Efficacy and Safety of Oral Once-Daily Vonoprazan (TAK-438) in Participants With Erosive Esophagitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02388724
Recruitment Status : Completed
First Posted : March 17, 2015
Results First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Erosive Esophagitis
Interventions Drug: Vonoprazan
Drug: Lansoprazole
Drug: Vonoprazan Placebo
Drug: Lansoprazole Placebo
Enrollment 481
Recruitment Details Participants took part in the study at 56 investigative sites in China, Korea, Taiwan, and Malaysia from 24 March 2015 to 27 July 2017.
Pre-assignment Details Participants with a diagnosis of erosive esophagitis were enrolled in a 1:1 ratio in one of two treatment groups, TAK-438 20 mg once daily (QD) or lansoprazole 30 mg QD.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks. Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Period Title: Overall Study
Started 244 237
Safety Set: Randomized But Not Treated 0 2
Completed [1] 232 224
Not Completed 12 13
Reason Not Completed
Reason not Specified             0             1
Major Protocol Deviation             3             3
Pretreatment Event/Adverse Event             3             2
Voluntary Withdrawal             6             5
Randomized but not Treated             0             2
[1]
Completed=Completed Treatment
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg Total
Hide Arm/Group Description Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks. Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 244 237 481
Hide Baseline Analysis Population Description
Randomized set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 244 participants 237 participants 481 participants
54.1  (13.16) 53.8  (12.53) 53.9  (12.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 244 participants 237 participants 481 participants
Female
68
  27.9%
58
  24.5%
126
  26.2%
Male
176
  72.1%
179
  75.5%
355
  73.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian Number Analyzed 244 participants 237 participants 481 participants
244
 100.0%
237
 100.0%
481
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Asia Number Analyzed 244 participants 237 participants 481 participants
China
143
  58.6%
133
  56.1%
276
  57.4%
Malaysia
21
   8.6%
24
  10.1%
45
   9.4%
South Korea
52
  21.3%
55
  23.2%
107
  22.2%
Taiwan
28
  11.5%
25
  10.5%
53
  11.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 244 participants 237 participants 481 participants
166.1  (8.24) 166.3  (8.80) 166.2  (8.52)
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 244 participants 235 participants 479 participants
68.48  (12.311) 70.26  (12.133) 69.35  (12.243)
[1]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms per square meter (kg/m^2)
Number Analyzed 244 participants 235 participants 479 participants
24.70  (3.389) 25.31  (3.430) 25.00  (3.419)
[1]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
Smoking Classification  
Measure Type: Count of Participants
Unit of measure:  Participants
Never Smoked Number Analyzed 244 participants 237 participants 481 participants
157
  64.3%
137
  57.8%
294
  61.1%
Current Smoker Number Analyzed 244 participants 237 participants 481 participants
48
  19.7%
64
  27.0%
112
  23.3%
Ex-Smoker Number Analyzed 244 participants 237 participants 481 participants
39
  16.0%
36
  15.2%
75
  15.6%
Consumption of Alcohol  
Measure Type: Count of Participants
Unit of measure:  Participants
Drink Everyday Number Analyzed 244 participants 237 participants 481 participants
13
   5.3%
12
   5.1%
25
   5.2%
Drink a Couple of Days Per Week Number Analyzed 244 participants 237 participants 481 participants
32
  13.1%
40
  16.9%
72
  15.0%
Drink a Couple of Days Per Month Number Analyzed 244 participants 237 participants 481 participants
57
  23.4%
48
  20.3%
105
  21.8%
Never Drink Number Analyzed 244 participants 237 participants 481 participants
142
  58.2%
137
  57.8%
279
  58.0%
Consumption of Caffeine   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 243 participants 237 participants 480 participants
58
  23.9%
52
  21.9%
110
  22.9%
No Number Analyzed 243 participants 237 participants 480 participants
185
  76.1%
185
  78.1%
370
  77.1%
[1]
Measure Analysis Population Description: The number of participants in the Vonoprazan 20 mg arm with non-missing data obtained from the case report form / electronic data capture was 243.
History of H. pylori Eradication Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes (End of Treatment: Within the Past 1 Year) Number Analyzed 244 participants 237 participants 481 participants
6
   2.5%
4
   1.7%
10
   2.1%
Yes (End of Treatment: More than 1 Year) Number Analyzed 244 participants 237 participants 481 participants
18
   7.4%
22
   9.3%
40
   8.3%
No Number Analyzed 244 participants 237 participants 481 participants
220
  90.2%
211
  89.0%
431
  89.6%
H. pylori Infection Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Positive Number Analyzed 241 participants 234 participants 475 participants
36
  14.9%
38
  16.2%
74
  15.6%
Negative Number Analyzed 241 participants 234 participants 475 participants
205
  85.1%
196
  83.8%
401
  84.4%
[1]
Measure Analysis Population Description: The number of participants in the Vonoprazan 20 mg and Lansoprazole 30 mg arms with non-missing data obtained from the case report form / electronic data capture was 241 and 234, respectively.
LA Classification for Diagnosis and Grading of Erosive Esophagitis   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Grade O Number Analyzed 244 participants 235 participants 479 participants
0
   0.0%
0
   0.0%
0
   0.0%
Grade A Number Analyzed 244 participants 235 participants 479 participants
76
  31.1%
83
  35.3%
159
  33.2%
Grade B Number Analyzed 244 participants 235 participants 479 participants
92
  37.7%
84
  35.7%
176
  36.7%
Grade C Number Analyzed 244 participants 235 participants 479 participants
58
  23.8%
58
  24.7%
116
  24.2%
Grade D Number Analyzed 244 participants 235 participants 479 participants
18
   7.4%
10
   4.3%
28
   5.8%
[1]
Measure Description: Grade O (no mucosal breaks); Grade A (one or more mucosal breaks no longer than 5 millimeters [mm], none of which extends between the tops of the mucosal folds); Grade B (one or more mucosal breaks more than 5 mm long, none of which extends between the tops of 2 mucosal folds); Grade C (mucosal breaks that extend between the tops of 2 or more mucosal folds, but which involve less than 75% of esophageal circumference), Grade D mucosal breaks which involve at least 75% of esophageal circumference.
[2]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
Barrett's Mucosa   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Present (3 cm or Greater) Number Analyzed 244 participants 235 participants 479 participants
7
   2.9%
7
   3.0%
14
   2.9%
Present (Less than 3 cm) Number Analyzed 244 participants 235 participants 479 participants
15
   6.1%
10
   4.3%
25
   5.2%
Absent Number Analyzed 244 participants 235 participants 479 participants
216
  88.5%
212
  90.2%
428
  89.4%
Unknown Number Analyzed 244 participants 235 participants 479 participants
6
   2.5%
6
   2.6%
12
   2.5%
[1]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
Esophageal Hiatal Hernia   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Present (2 cm or Greater) Number Analyzed 244 participants 235 participants 479 participants
36
  14.8%
39
  16.6%
75
  15.7%
Present (Less than 2 cm) Number Analyzed 244 participants 235 participants 479 participants
24
   9.8%
24
  10.2%
48
  10.0%
Absent Number Analyzed 244 participants 235 participants 479 participants
180
  73.8%
166
  70.6%
346
  72.2%
Unknown Number Analyzed 244 participants 235 participants 479 participants
4
   1.6%
6
   2.6%
10
   2.1%
[1]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
Diary for Gastrointestinal Symptoms: Mean Severity of Heartburn Symptoms   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 244 participants 235 participants 479 participants
0.797  (0.7153) 0.767  (0.6408) 0.782  (0.6792)
[1]
Measure Description: 0=None (no symptoms), 1=Mild (occasional symptoms, can be ignored, does not influence daily routine), 2=Moderate (symptoms cannot be ignored and/or occasionally influence daily routine), 3=Severe (symptoms present most of the day and/or regularly influence daily routine)
[2]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
Mean Severity of Gastric Acid Regurgitation   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 244 participants 235 participants 479 participants
0.772  (0.6765) 0.727  (0.6731) 0.750  (0.6745)
[1]
Measure Description: 0=None (no symptoms), 1=Mild (occasional symptoms, can be ignored, does not influence daily routine), 2=Moderate (symptoms cannot be ignored and/or occasionally influence daily routine), 3=Severe (symptoms present most of the day and/or regularly influence daily routine)
[2]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
Health-Related Quality of Life (HRQoL) EQ-5D-5L Index Value   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 244 participants 235 participants 479 participants
0.9503  (0.07278) 0.9486  (0.06466) 0.9495  (0.06885)
[1]
Measure Description: The EQ-5D-5L Index assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are combined and converted to a single index score. The lowest possible score is -0.39 (unable to walk, care for oneself, do usual activities; having extreme pain or discomfort; extreme anxiety or depression) and the highest is 1.00 (no problems in all 5 dimensions).
[2]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
EuroQol-visual analogue scales (EQ VAS) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 244 participants 235 participants 479 participants
85.7  (10.88) 85.2  (11.56) 85.4  (11.21)
[1]
Measure Description: The EQ VAS is a questionnaire asking the participant to mark health status on a 20 cm vertical scale, ranging from 0 (worst health you can imagine) to 100 (best health you can imagine).
[2]
Measure Analysis Population Description: Data for 2 participants in the Lansoprazole 30 mg arm were missing because they were randomized, but terminated early due to voluntary withdrawal.
1.Primary Outcome
Title Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase
Hide Description Endoscopic healing is defined as participants endoscopically diagnosed as Los Angeles classification grade O during the treatment phase. Grade O indicates there are no mucosal breaks in the mucosa.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline endoscopy.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 238 230
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
92.4
(88.310 to 95.456)
91.3
(86.890 to 94.607)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vonoprazan 20 mg, Lansoprazole 30 mg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments If the lower bound of the 95% confidence intervals of the difference was more than -10% (non-inferiority margin), non-inferiority for Vonoprazan relative to Lansoprazole was declared.
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-3.822 to 6.087
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment
Hide Description Endoscopic healing is defined as participants endoscopically diagnosed as Los Angeles classification grade O during the treatment phase. Grade O indicates there are no mucosal breaks in the mucosa.
Time Frame Week 2 and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline endoscopy. Number analyzed is the number of participants with data available at the given time-point.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 238 230
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2 Weeks Number Analyzed 236 participants 227 participants
75.0
(68.970 to 80.391)
67.8
(61.341 to 73.869)
4 Weeks Number Analyzed 238 participants 230 participants
85.3
(80.146 to 89.538)
83.5
(78.035 to 88.035)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vonoprazan 20 mg, Lansoprazole 30 mg
Comments 2 Weeks
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 7.2
Confidence Interval (2-Sided) 95%
-1.054 to 15.371
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Vonoprazan 20 mg, Lansoprazole 30 mg
Comments 4 Weeks
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-4.763 to 8.395
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)
Hide Description An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be 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.
Time Frame On or after the start of study drug (Day 1) to 14 days after the last dose of study medication (up to 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who took at least 1 dose of study medication.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 244 235
Measure Type: Count of Participants
Unit of Measure: Participants
93
  38.1%
86
  36.6%
4.Secondary Outcome
Title Number of Participants With Markedly Abnormal Clinical Laboratory Findings
Hide Description Clinical Laboratory Safety tests included Chemistry, Hematology and Urinalysis. Number of participants with any markedly abnormal values in laboratory tests collected throughout study is reported. ALT = alanine aminotransferase, AST = aspartate aminotransferase, GGT = gamma-glutamyl transferase, CPK = creatine phosphokinase, BUN = blood urea nitrogen, LLN = lower limit of normal or lower reference limit, ULN = upper limit of normal or upper reference limit, g/L = grams per liter, U/L = units per liter, mmol/L = millimoles per liter, pmol/L = picomoles per liter.
Time Frame From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 244 235
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin (<0.8 x LLN g/L) Number Analyzed 239 participants 231 participants
0
   0.0%
1
   0.4%
Neutrophils (<0.5 x LLN %) Number Analyzed 239 participants 230 participants
0
   0.0%
2
   0.9%
Eosinophils (>2 x ULN %) Number Analyzed 239 participants 230 participants
1
   0.4%
0
   0.0%
Lymphocytes (>1.5 x ULN %) Number Analyzed 239 participants 230 participants
0
   0.0%
2
   0.9%
ALT (>3 x ULN U/L) Number Analyzed 238 participants 231 participants
0
   0.0%
2
   0.9%
AST (>3 x ULN U/L) Number Analyzed 238 participants 231 participants
0
   0.0%
1
   0.4%
GGT (>3 x ULN U/L) Number Analyzed 238 participants 231 participants
4
   1.7%
3
   1.3%
CPK (>5 x ULN U/L) Number Analyzed 238 participants 231 participants
1
   0.4%
2
   0.9%
Total Protein (>1.2 x ULN g/L) Number Analyzed 238 participants 231 participants
0
   0.0%
1
   0.4%
BUN (>10.7 mmol/L) Number Analyzed 238 participants 231 participants
1
   0.4%
1
   0.4%
Total Cholesterol (>7.72 mmol/L) Number Analyzed 238 participants 231 participants
3
   1.3%
2
   0.9%
Triglycerides (>2.5 x ULN mmol/L) Number Analyzed 238 participants 231 participants
6
   2.5%
3
   1.3%
Vitamin B12 (<92 pmol/L) Number Analyzed 236 participants 227 participants
0
   0.0%
1
   0.4%
5.Secondary Outcome
Title Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
Hide Description Number of participants with any markedly abnormal 12-lead ECG findings is reported. bpm = beats per minute, msec = milliseconds, CHG= change from baseline.
Time Frame From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 244 235
Measure Type: Count of Participants
Unit of Measure: Participants
Heart Rate (<50 bpm) Number Analyzed 236 participants 228 participants
6
   2.5%
7
   3.1%
QT Interval (≥460 msec) Number Analyzed 236 participants 228 participants
7
   3.0%
10
   4.4%
QTcF Interval (≥500, or ≥450 with CHG ≥30 msec) Number Analyzed 236 participants 228 participants
3
   1.3%
5
   2.2%
6.Secondary Outcome
Title Number of Participants With Markedly Abnormal Vital Sign Measurements
Hide Description Number of participants with any markedly abnormal vital signs measurements is reported. Vital signs included body temperature (oral, tympanic, or infra-axillary measurement), sitting blood pressure (5 minutes), and pulse. °C = degrees Celsius, mmHg = millimeters of mercury, bpm = beats per minute.
Time Frame From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 244 235
Measure Type: Count of Participants
Unit of Measure: Participants
Body Temperature (<35.6 °C) Number Analyzed 241 participants 231 participants
10
   4.1%
3
   1.3%
Body Temperature (>37.7 °C) Number Analyzed 241 participants 231 participants
2
   0.8%
0
   0.0%
Systolic Blood Pressure (<85 mmHg) Number Analyzed 241 participants 231 participants
1
   0.4%
1
   0.4%
Diastolic Blood Pressure (>110 mmHg) Number Analyzed 241 participants 231 participants
1
   0.4%
0
   0.0%
Pulse (<50 bpm) Number Analyzed 241 participants 231 participants
2
   0.8%
2
   0.9%
7.Secondary Outcome
Title Change From Baseline in Serum Gastrin
Hide Description The change between the serum gastrin values collected at Weeks 2, 4, and 8 relative to baseline.
Time Frame Baseline and Weeks 2, 4, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 244 235
Mean (Standard Deviation)
Unit of Measure: pmol/L
Baseline Number Analyzed 230 participants 229 participants
2.77  (4.084) 3.65  (8.622)
Change at Week 2 Number Analyzed 220 participants 219 participants
31.45  (28.995) 8.33  (10.190)
Change at Week 4 Number Analyzed 57 participants 71 participants
29.68  (29.189) 6.81  (9.969)
Change at Week 8 Number Analyzed 30 participants 31 participants
36.53  (37.108) 4.71  (7.727)
8.Secondary Outcome
Title Change From Baseline in Serum Pepsinogen I
Hide Description The change between the serum pepsinogen I values collected at Weeks 2, 4, and 8 relative to baseline.
Time Frame Baseline and Weeks 2, 4, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 244 235
Mean (Standard Deviation)
Unit of Measure: micrograms per liter (ug/L)
Baseline Number Analyzed 238 participants 231 participants
97.6  (53.54) 99.8  (61.99)
Change at Week 2 Number Analyzed 227 participants 223 participants
456.5  (308.22) 129.3  (138.24)
Change at Week 4 Number Analyzed 57 participants 71 participants
421.8  (324.06) 118.3  (113.24)
Change at Week 8 Number Analyzed 30 participants 30 participants
326.8  (233.80) 117.8  (98.03)
9.Secondary Outcome
Title Change From Baseline in Serum Pepsinogen II
Hide Description The change between the serum pepsinogen II values collected at Weeks 2, 4, and 8 relative to baseline.
Time Frame Baseline and Weeks 2, 4, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description:
Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.
Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Overall Number of Participants Analyzed 244 235
Mean (Standard Deviation)
Unit of Measure: ug/L
Baseline Number Analyzed 235 participants 231 participants
7.5  (5.50) 7.8  (5.77)
Change at Week 2 Number Analyzed 227 participants 225 participants
44.9  (31.31) 8.8  (9.63)
Change at Week 4 Number Analyzed 56 participants 71 participants
40.7  (26.10) 7.2  (5.99)
Change at Week 8 Number Analyzed 29 participants 31 participants
31.0  (20.03) 8.0  (8.46)
Time Frame Up to 10 weeks (8 weeks of treatment and 2 weeks of post-treatment follow-up period)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal physical examination and laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Vonoprazan 20 mg Lansoprazole 30 mg
Hide Arm/Group Description Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks. Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
All-Cause Mortality
Vonoprazan 20 mg Lansoprazole 30 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/244 (0.00%)   0/235 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Vonoprazan 20 mg Lansoprazole 30 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   3/244 (1.23%)   3/235 (1.28%) 
Eye disorders     
Glaucoma  1  0/244 (0.00%)  1/235 (0.43%) 
Gastrointestinal disorders     
Large intestine polyp  1  0/244 (0.00%)  1/235 (0.43%) 
Hepatobiliary disorders     
Bile duct stone  1  1/244 (0.41%)  0/235 (0.00%) 
Infections and infestations     
Gastroenteritis  1  0/244 (0.00%)  1/235 (0.43%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon adenoma  1  1/244 (0.41%)  0/235 (0.00%) 
Nervous system disorders     
Cerebral infarction  1  1/244 (0.41%)  0/235 (0.00%) 
1
Term from vocabulary, MedDRA version: 18.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vonoprazan 20 mg Lansoprazole 30 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   13/244 (5.33%)   4/235 (1.70%) 
Investigations     
Blood gastrin increased  1  13/244 (5.33%)  4/235 (1.70%) 
1
Term from vocabulary, MedDRA version: 18.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02388724     History of Changes
Other Study ID Numbers: TAK-438_303
U1111-1138-4788 ( Registry Identifier: UTN (WHO) )
CTR20150040 ( Registry Identifier: CNDA CTR )
First Submitted: March 9, 2015
First Posted: March 17, 2015
Results First Submitted: July 24, 2018
Results First Posted: June 3, 2019
Last Update Posted: June 3, 2019