Special Drug Use Surveillance of Vonoprazan for "Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Non-steroidal Anti-inflammatory Drugs: Long-term Use"

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03214198
• Collaborator: (none)
• Enrollment: 1,304
• Location: 1
• Actual Duration (Months): 43.9
• Patients Per Site Per Month: 29.7

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and efficacy of long-term administration of Vonoprazan tablets (Takecab tablets) for up to 12 months in the routine clinical setting in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs).

Condition or Disease	Intervention/Treatment	Phase
A History of Gastric or Duodenal Ulcers	Drug: Vonoprazan

Detailed Description

The drug being tested in this study is called Vonoprazan. Vonoprazan is being tested to treat people who have a history of gastric or duodenal ulcers.

This study will look at the safety and efficacy of long-term administration of Vonoprazan tablets for up to 12 months in the routine clinical setting in patients receiving NSAIDs.

The study will enroll approximately 1000 participants.

• Vonoprazan 10 mg

This multi-center observational survey will be conducted in Japan.

Study Design

• Study Type: Observational
• Actual Enrollment: 1304 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Special Drug Use Surveillance of Takecab Tablets for "Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Non-steroidal Anti-inflammatory Drugs: Long-term Use"
• Actual Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Apr 30, 2020
• Actual Study Completion Date: Apr 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Vonoprazan 10 mg The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.	Drug: Vonoprazan; Vonoprazan tablets; Other Names: Takecab tablets TAK-438

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Had One or More Adverse Drug Reactions [Up to 12 months]

   An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to administered drug.

Secondary Outcome Measures

1. Percentage of Participants With Gastric Ulcers [Up to 12 months]

   The presence or absence of onset of gastric ulcers was reported. Reporting data was total percentage of participants with gastric ulcers.

2. Percentage of Participants With Duodenal Ulcers [Up to 12 months]

   The presence or absence of onset of duodenal ulcers was reported. Reporting data was total percentage of participants with duodenal ulcers.

3. Percentage of Participants With Gastric Hemorrhagic Lesions [Up to 12 months]

   The presence or absence of onset of gastric hemorrhagic lesions was reported. Reporting data was total percentage of participants with gastric hemorrhagic lesions.

4. Percentage of Participants With Duodenal Hemorrhagic Lesions [Up to 12 months]

   The presence or absence of onset of duodenal hemorrhagic lesions was reported. Reporting data was total percentage of participants with duodenal hemorrhagic lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with a history of gastric or duodenal ulcer

Exclusion Criteria:

• Participants with gastric or duodenal ulcer at initiation of vonoprazan therapy

• Participants with active upper gastrointestinal haemorrhage at initiation of vonoprazan therapy

• Participants with a history of hypersensitivity to any ingredients of vonoprazan Tablets

• Participants receiving atazanavir sulfate or rilpivirine hydrochloride

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Takeda Selected Site	Tokyo		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jun 12, 2020
• Statistical Analysis Plan - Nov 9, 2020

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03214198
• Other Study ID Numbers: Vonoprazan-5005; JapicCTI-163436
• First Posted: Jul 11, 2017
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Duodenal Ulcer; Ulcer; Recurrence

Study Results

Participant Flow

Recruitment Details	Participants took part in the survey at 145 investigative sites in Japan, from 01 September 2016 to 30 April 2019.
Pre-assignment Detail	Participants with a historical diagnosis of gastric or duodenal ulcers were enrolled. Participants received vonoprazan as part of a routine medical care.

Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
Period Title: Overall Study
STARTED	1304
COMPLETED	1268
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
Overall Participants	1268
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	70.9 (13.46)
Sex: Female, Male (Count of Participants)
Female	839 66.2%
Male	429 33.8%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
Japan	1268 100%
Medical History (Gastric Ulcer) (Count of Participants)
Count of Participants [Participants]	1142 90.1%
Medical History (Duodenal Ulcer) (Count of Participants)
Count of Participants [Participants]	154 12.1%
Reason for Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Rheumatoid Arthritis (Count of Participants)
Count of Participants [Participants]	168 13.2%
Reason for Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) , Osteoarthritis (Count of Participants)
Count of Participants [Participants]	879 69.3%
Reason for Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) , Others (Count of Participants)
Count of Participants [Participants]	259 20.4%
Healthcare Category (Count of Participants)
Outpatient	1233 97.2%
Inpatient	35 2.8%
Predisposition to Hypersensitivity (Count of Participants)
Had Predisposition to Hypersensitivity	60 4.7%
Had No Predisposition to Hypersensitivity	1052 83%
Unknown	156 12.3%
Medical Complications (Count of Participants)
Had Medical Complications	929 73.3%
Had No Medical Complications	339 26.7%
Height (Centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters (cm)]	155.63 (9.603)
Weight (Kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (kg)]	57.91 (12.480)
BMI (Kilogram (kg)/meter (m)^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilogram (kg)/meter (m)^2]	23.79 (4.055)
Helicobacter Pylori Infection (Count of Participants)
Positive	24 1.9%
Negative	474 37.4%
Unknown	770 60.7%
Smoking Classification (Count of Participants)
Never Smoked	627 49.4%
Current Smoker	108 8.5%
Ex-Smoker	236 18.6%
Unknown	297 23.4%
Drinking Habits (Count of Participants)
Current Drinker	154 12.1%
Never Drank or Ex Drinker	848 66.9%
Unknown	266 21%
Presence of Stress as a Risk Factor of Gastric or Duodenal Ulcer (Count of Participants)
Present	162 12.8%
Absent	670 52.8%
Unknown	436 34.4%
Prior Treatment with Acid Suppressants to Prevent Recurrent Gastric or Duodenal Ulcer (Count of Participants)
Had Prior Treatment with Acid Suppressants	505 39.8%
Had No Prior Treatment with Acid Suppressants	661 52.1%
Unknown	102 8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Had One or More Adverse Drug Reactions
Description	An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to administered drug.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.

Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
Measure Participants	1268
Number [Percentage of Participants]	0.71 0.1%

2. Secondary Outcome

Title	Percentage of Participants With Gastric Ulcers
Description	The presence or absence of onset of gastric ulcers was reported. Reporting data was total percentage of participants with gastric ulcers.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy assessment population, The efficacy assessment population was defined as participants who completed the survey and had efficacy data at baseline and post-baseline time points available.

Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
Measure Participants	1245
Number [Percentage of Participants]	0.56 0%

3. Secondary Outcome

Title	Percentage of Participants With Duodenal Ulcers
Description	The presence or absence of onset of duodenal ulcers was reported. Reporting data was total percentage of participants with duodenal ulcers.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy assessment population, The efficacy assessment population was defined as participants who completed the survey and had efficacy data at baseline and post-baseline time points available.

Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
Measure Participants	1245
Number [Percentage of Participants]	0.16 0%

4. Secondary Outcome

Title	Percentage of Participants With Gastric Hemorrhagic Lesions
Description	The presence or absence of onset of gastric hemorrhagic lesions was reported. Reporting data was total percentage of participants with gastric hemorrhagic lesions.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy assessment population, The efficacy assessment population was defined as participants who completed the survey and had efficacy data at baseline and post-baseline time points available.

Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
Measure Participants	1245
Number [Percentage of Participants]	0.24 0%

5. Secondary Outcome

Title	Percentage of Participants With Duodenal Hemorrhagic Lesions
Description	The presence or absence of onset of duodenal hemorrhagic lesions was reported. Reporting data was total percentage of participants with duodenal hemorrhagic lesions.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy assessment population, The efficacy assessment population was defined as participants who completed the survey and had efficacy data at baseline and post-baseline time points available.

Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
Measure Participants	1245
Number [Percentage of Participants]	0.08 0%

Adverse Events

Time Frame	Up to 12 months
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
Arm/Group Title	Vonoprazan 10 mg
Arm/Group Description	The usual adult dosage for oral use is 10 mg of Vonoprazan administered once daily. Participants will receive interventions as part of routine medical care.
All Cause Mortality
	Vonoprazan 10 mg
	Affected / at Risk (%)	# Events
Total	7/1268 (0.6%)
Serious Adverse Events
	Vonoprazan 10 mg
	Affected / at Risk (%)	# Events
Total	17/1268 (1.3%)
Eye disorders
Ulcerative keratitis	1/1268 (0.1%)
Hepatobiliary disorders
Hepatic function abnormal	1/1268 (0.1%)
Jaundice cholestatic	1/1268 (0.1%)
Infections and infestations
Pneumonia	1/1268 (0.1%)
Sepsis	1/1268 (0.1%)
Injury, poisoning and procedural complications
Injury	1/1268 (0.1%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/1268 (0.1%)
Spinal stenosis	1/1268 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	1/1268 (0.1%)
Pancreatic carcinoma	1/1268 (0.1%)
Pancreatic carcinoma metastatic	1/1268 (0.1%)
Nervous system disorders
Cerebral infarction	1/1268 (0.1%)
Parkinson's disease	1/1268 (0.1%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/1268 (0.2%)
Respiratory, thoracic and mediastinal disorders
Asphyxia	1/1268 (0.1%)
Aspiration	1/1268 (0.1%)
Chronic respiratory failure	1/1268 (0.1%)
Interstitial lung disease	1/1268 (0.1%)
Skin and subcutaneous tissue disorders
Rash	1/1268 (0.1%)
Other (Not Including Serious) Adverse Events
	Vonoprazan 10 mg
	Affected / at Risk (%)	# Events
Total	21/1268 (1.7%)
Gastrointestinal disorders
Diarrhoea	4/1268 (0.3%)
Gastrooesophageal reflux disease	2/1268 (0.2%)
Hepatobiliary disorders
Hepatic function abnormal	3/1268 (0.2%)
Infections and infestations
Bronchitis	2/1268 (0.2%)
Cystitis	2/1268 (0.2%)
Nasopharyngitis	2/1268 (0.2%)
Pharyngitis	2/1268 (0.2%)
Helicobacter infection	2/1268 (0.2%)
Skin and subcutaneous tissue disorders
Eczema	2/1268 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.