NCT02388724

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

Completed Phase 3 Results posted Last updated 3 June 2019

What this trial tests

Phase 3 trial testing Vonoprazan in Erosive Esophagitis in 481 participants. Completed in 27 July 2017.

Timeline

24 March 2015

Primary endpoint
27 July 2017

27 July 2017

Quick facts

Lead sponsor	Takeda
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	481
Start date	24 March 2015
Primary completion	27 July 2017
Estimated completion	27 July 2017
Sites	64 locations across China, Taiwan, Malaysia, South Korea

Drugs / interventions tested

• Vonoprazan — full drug profile →
• Lansoprazole (lansoprazole) — full drug profile →
• Vonoprazan Placebo — full drug profile →
• Lansoprazole Placebo — full drug profile →

Conditions studied

• Erosive Esophagitis — all drugs for Erosive Esophagitis →

Sponsor

Takeda — full company profile →

Who can join

18 and older, any sex, with Erosive Esophagitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase Primary · 8 weeks

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.

Group	Value	95% CI
Vonoprazan 20 mg	92.4	88.310 – 95.456
Lansoprazole 30 mg	91.3	86.890 – 94.607

Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment Secondary · Week 2 and Week 4

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.

2 Weeks

Group	Value	95% CI
Vonoprazan 20 mg	75.0	68.970 – 80.391
Lansoprazole 30 mg	67.8	61.341 – 73.869

4 Weeks

Group	Value	95% CI
Vonoprazan 20 mg	85.3	80.146 – 89.538
Lansoprazole 30 mg	83.5	78.035 – 88.035

Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE) Secondary · On or after the start of study drug (Day 1) to 14 days after the last dose of study medication (up to 10 weeks)

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.

Group	Value	95% CI
Vonoprazan 20 mg	93
Lansoprazole 30 mg	86

Number of Participants With Markedly Abnormal Clinical Laboratory Findings Secondary · From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)

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.

Hemoglobin (<0.8 x LLN g/L)

Group	Value	95% CI
Vonoprazan 20 mg	0
Lansoprazole 30 mg	1

Neutrophils (<0.5 x LLN %)

Group	Value	95% CI
Vonoprazan 20 mg	0
Lansoprazole 30 mg	2

Eosinophils (>2 x ULN %)

Group	Value	95% CI
Vonoprazan 20 mg	1
Lansoprazole 30 mg	0

Lymphocytes (>1.5 x ULN %)

Group	Value	95% CI
Vonoprazan 20 mg	0
Lansoprazole 30 mg	2

ALT (>3 x ULN U/L)

Group	Value	95% CI
Vonoprazan 20 mg	0
Lansoprazole 30 mg	2

AST (>3 x ULN U/L)

Group	Value	95% CI
Vonoprazan 20 mg	0
Lansoprazole 30 mg	1

GGT (>3 x ULN U/L)

Group	Value	95% CI
Vonoprazan 20 mg	4
Lansoprazole 30 mg	3

CPK (>5 x ULN U/L)

Group	Value	95% CI
Vonoprazan 20 mg	1
Lansoprazole 30 mg	2

Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings Secondary · From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)

Number of participants with any markedly abnormal 12-lead ECG findings is reported. bpm = beats per minute, msec = milliseconds, CHG= change from baseline.

Heart Rate (<50 bpm)

Group	Value	95% CI
Vonoprazan 20 mg	6
Lansoprazole 30 mg	7

QT Interval (≥460 msec)

Group	Value	95% CI
Vonoprazan 20 mg	7
Lansoprazole 30 mg	10

QTcF Interval (≥500, or ≥450 with CHG ≥30 msec)

Group	Value	95% CI
Vonoprazan 20 mg	3
Lansoprazole 30 mg	5

Number of Participants With Markedly Abnormal Vital Sign Measurements Secondary · From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)

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.

Body Temperature (<35.6 °C)

Group	Value	95% CI
Vonoprazan 20 mg	10
Lansoprazole 30 mg	3

Body Temperature (>37.7 °C)

Group	Value	95% CI
Vonoprazan 20 mg	2
Lansoprazole 30 mg	0

Systolic Blood Pressure (<85 mmHg)

Group	Value	95% CI
Vonoprazan 20 mg	1
Lansoprazole 30 mg	1

Diastolic Blood Pressure (>110 mmHg)

Group	Value	95% CI
Vonoprazan 20 mg	1
Lansoprazole 30 mg	0

Pulse (<50 bpm)

Group	Value	95% CI
Vonoprazan 20 mg	2
Lansoprazole 30 mg	2

Change From Baseline in Serum Gastrin Secondary · Baseline and Weeks 2, 4, and 8

The change between the serum gastrin values collected at Weeks 2, 4, and 8 relative to baseline.

Baseline

Group	Value	95% CI
Vonoprazan 20 mg	2.77	± 4.084
Lansoprazole 30 mg	3.65	± 8.622

Change at Week 2

Group	Value	95% CI
Vonoprazan 20 mg	31.45	± 28.995
Lansoprazole 30 mg	8.33	± 10.190

Change at Week 4

Group	Value	95% CI
Vonoprazan 20 mg	29.68	± 29.189
Lansoprazole 30 mg	6.81	± 9.969

Change at Week 8

Group	Value	95% CI
Vonoprazan 20 mg	36.53	± 37.108
Lansoprazole 30 mg	4.71	± 7.727

Change From Baseline in Serum Pepsinogen I Secondary · Baseline and Weeks 2, 4, and 8

The change between the serum pepsinogen I values collected at Weeks 2, 4, and 8 relative to baseline.

Baseline

Group	Value	95% CI
Vonoprazan 20 mg	97.6	± 53.54
Lansoprazole 30 mg	99.8	± 61.99

Change at Week 2

Group	Value	95% CI
Vonoprazan 20 mg	456.5	± 308.22
Lansoprazole 30 mg	129.3	± 138.24

Change at Week 4

Group	Value	95% CI
Vonoprazan 20 mg	421.8	± 324.06
Lansoprazole 30 mg	118.3	± 113.24

Change at Week 8

Group	Value	95% CI
Vonoprazan 20 mg	326.8	± 233.80
Lansoprazole 30 mg	117.8	± 98.03

Change From Baseline in Serum Pepsinogen II Secondary · Baseline and Weeks 2, 4, and 8

The change between the serum pepsinogen II values collected at Weeks 2, 4, and 8 relative to baseline.

Baseline

Group	Value	95% CI
Vonoprazan 20 mg	7.5	± 5.50
Lansoprazole 30 mg	7.8	± 5.77

Change at Week 2

Group	Value	95% CI
Vonoprazan 20 mg	44.9	± 31.31
Lansoprazole 30 mg	8.8	± 9.63

Change at Week 4

Group	Value	95% CI
Vonoprazan 20 mg	40.7	± 26.10
Lansoprazole 30 mg	7.2	± 5.99

Change at Week 8

Group	Value	95% CI
Vonoprazan 20 mg	31.0	± 20.03
Lansoprazole 30 mg	8.0	± 8.46

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 10 weeks (8 weeks of treatment and 2 weeks of post-treatment follow-up period). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vonoprazan 20 mg

Serious: 3/244 (1%)

Deaths: 0/244

Lansoprazole 30 mg

Serious: 3/235 (1%)

Deaths: 0/235

Serious adverse events (6 terms)

Reaction	System	Vonoprazan 20 mg	Lansoprazole 30 mg
Glaucoma	Eye disorders	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Bile duct stone	Hepatobiliary disorders	—	—
Gastroenteritis	Infections and infestations	—	—
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cerebral infarction	Nervous system disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Vonoprazan 20 mg	Lansoprazole 30 mg
Blood gastrin increased	Investigations	—	—

Most-reported serious reactions: Glaucoma, Large intestine polyp, Bile duct stone, Gastroenteritis, Colon adenoma, Cerebral infarction.

Data from ClinicalTrials.gov NCT02388724 adverse events section.

Sponsor's own description

The purpose of the study is to demonstrate the efficacy of vonoprazan (TAK-438) versus lansoprazole in the treatment of erosive esophagitis classified as Los Angeles (LA) classification grades A to D at Week 8.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis.
   Xiao Y, Zhang S, Dai N, Fei G, et al · · 2020 · cited 103× · PMID 31409606 · DOI 10.1136/gutjnl-2019-318365
2. Vonoprazan 10 mg or 20 mg vs. lansoprazole 15 mg as maintenance therapy in Asian patients with healed erosive esophagitis: A randomized controlled trial.
   Xiao Y, Qian J, Zhang S, Dai N, et al · · 2024 · cited 11× · PMID 38654422 · DOI 10.1097/cm9.0000000000003068