Phase 3 Study of TAK-438 10 mg in the Treatment of Non-Erosive Gastroesophageal Reflux Disease (NERD)

NCT02954848 | Completed Phase 3 Results

• 3 other identifiers: Vonoprazan-3001U1111-1188-1784JapicCTI-163413
• Study Type: interventional
• Target: 484
• Locations: 1 country
• Sites: 30

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of oral TAK-438 10 mg once-daily in the treatment of non-erosive gastroesophageal reflux disease (NERD).

Conditions

Non-erosive Gastroesophageal Reflux Disease

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (3)

• Percentage of Days Without Symptoms of Heartburn

  Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Reported data was the percentage of days for each group, calculated by the number of days without heartburn divided by the number of days of treatment period.

  Up to Week 4

• Cumulative Rate of Improvement in Symptoms of Heartburn

  Heartburn symptoms were collected by participant diaries. Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. Cumulative rate of improvement was calculated as percentage of participants who experienced symptom improvement. Symptom improvement was defined as symptoms experienced on less than 2 days of the last 7 days. The cumulative data was collected between Day 0 and Day 24 and is reported for the following time points: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24. Data not collected were shown as NA = Not Applicable.

  Day 0 to Day 24

• Severity of Symptoms of Heartburn

  Participants recorded the presence and severity (Without symptom \[No symptom: 0, No hindrance to daily activities: 1\], With symptom \[Mild: 2, Moderate: 3, Severe: 4\]) of heartburn in a daily participant diary. The score range was 0-4, with the higher scores reflecting the greater severity. The severity of heartburn was calculated by the number of severity score in daily diaries.

  Up to Week 4

Secondary Outcomes (24)

• Percentage of Days Without Symptoms of Heartburn in Subgroup Stratified by Response (Improved or Not Improved) at Week 2

  Up to Week 4

• Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 1) at Week 2

  Day 0 to Day 22

• Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 1) at Week 2

  Day 0 to Day 24

• Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Improved Per Criteria 2) at Week 2

  Day 0 to Day 24

• Cumulative Rate of Improvement in Symptoms of Heartburn in Subgroup Stratified by Response (Not Improved Per Criteria 2) at Week 2

  Day 0 to Day 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

TAK-438 placebo-matching tablets, orally, once daily after breakfast for 1 week in run-in period followed by TAK-438 placebo-matching tablets, orally, once daily after breakfast for up to 4 weeks in treatment period.

Drug: Placebo

TAK-438 10 mg

EXPERIMENTAL

TAK-438 placebo-matching tablets, orally, once daily after breakfast for 1 week in run-in period followed by TAK-438 10 mg tablets, orally, once daily after breakfast for up to 4 weeks in treatment period.

Drug: Placebo; Drug: TAK-438 10 mg

Interventions

Placebo DRUG

TAK-438 placebo-matching tablets

Placebo; TAK-438 10 mg

TAK-438 10 mg DRUG

TAK-438 tablets

TAK-438 10 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written informed consent form prior to the initiation of any study procedures.
• The participant with NERD.
• The participant is endoscopically confirmed to have the modified Los Angeles (LA) Classification Grade N or M at the start of the run-in period (Visit 1).
• To allow efficacy evaluation in the participants with Grade N as well as in those with Grade M, the target number of participants in each grade is at least 30% of the total number of participants. Enrollment of patients with either Grade N or M will end when the number of enrolled participants with each grade exceeds 332, or 70% of the total planned number of participants.
• The participant experiences recurrent heartburn, on at least 2 days a week over the last 3 weeks prior to the start of the run-in period (Visit 1).
• The participant is either a male or female outpatient with a minimum age of 20 years at the time of informed consent signing. However, participants who are hospitalized only for examination purposes are also allowed to participate.
• A female participant of childbearing potential agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study, and for 4 weeks after the last dose of study drug.
• The participant's compliance to the study drug has been good (75% or better) in the run-in period.
• The participant has experienced heartburn on at least 2 days in the last 1 week prior to randomization.
• The participant has appropriately provided in the patient's diary all the required information during the run-in period.

You may not qualify if:

• The participant has received any investigational compound within 84 days prior to the first dose of study drug.
• The participant has received TAK-438 in a previous clinical study or as a therapeutic agent, except one with experience of receiving TAK-438 as an adjunct therapy for H. pylori eradication, who can be enrolled in this study.
• The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• The participant has donated at least 400 mL of blood within the 90 days prior to the start of the run-in period (Visit 1).
• Endoscopic examination for entering this study fails to diagnose NERD within 84 days before the start of the run-in period (Visit 1).
• The participant has any complications affecting the esophagus, including Barrett's esophagus (3 cm or more, long segment Barrett's esophagus \[LSBE\]), eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, and esophageal stenosis; a history of radiation therapy or cryotherapy for the esophagus; or caustic or physiochemical trauma (eg, esophageal sclerotherapy). However, participants with Barrett's mucosa (less than 3 cm, short segment Barrett's esophagus \[SSBE\]) or Schatzki's ring (a mucosal tissue ring lining the inferior esophageal sphincter) are permitted to participate.
• The participant has a history of surgery or treatment affecting gastroesophageal reflux, including fundoplication and mechanical dilatation for esophageal stenosis (except Schatzki's ring), or a history of gastric or duodenal surgery (except endoscopic removal of benign polyps).
• The participant has acute upper gastrointestinal bleeding or gastric or duodenal ulcer, characterized by a defective mucosa with white coating, within 30 days prior to the start of the run-in period (Visit 1). However, participants with gastric or duodenal erosion are permitted to participate.
• The participant has acute gastritis or acute exacerbation of chronic gastritis.
• The participant has, or has a history of, Zollinger-Ellison syndrome or gastric acid hypersecretion disorders.
• The participant has, or has a history of chest pain due to cardiac disease, or has chest pain suspectedly caused by cardiac disease within 1 year prior to the start of the run-in period (Visit 1).
• The participant has any other concurrent upper gastrointestinal symptoms more severe than heartburn.
• The participant has depression.
• The participant has, has a history of, or is suspected of functional upper gastrointestinal disorders, such as functional dyspepsia and functional heartburn diagnosed by the Rome IV criteria.
• The participant has a history of hypersensitivity or allergies to TAK-438 (including the formulation excipients).

Sponsors & Collaborators

• Takeda: lead

Study Sites (30)

Unknown Facility

Abiko, Chiba, Japan

Location

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Yachiyo, Chiba, Japan

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Kasuya-gun, Fukuoka, Japan

Location

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Kitakyushu, Fukuoka, Japan

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Wakasugi, Fukuoka, Japan

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Yukuhashi, Fukuoka, Japan

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Kōriyama, Fukushima, Japan

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Asahikawa, Hokkaido, Japan

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Sapporo, Hokkaido, Japan

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Yokohama, Kanagawa, Japan

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Suzaki, Kochi, Japan

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Kitakatsuragi, Nara, Japan

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Fujimi, Saitama, Japan

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Hiki-gun, Saitama, Japan

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Satte, Saitama, Japan

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Ōtawara, Tochigi, Japan

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Arakawa-ku, Tokyo, Japan

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Nakano-ku, Tokyo, Japan

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Setagaya-ku, Tokyo, Japan

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Shibuya-ku, Tokyo, Japan

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Toshima-ku, Tokyo, Japan

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Fukuoka, Japan

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Hiroshima, Japan

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Kochi, Japan

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Kumamoto, Japan

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Nagasaki, Japan

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Osaka, Japan

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Ōita, Japan

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Shizuoka, Japan

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Unknown Facility

Yamagata, Japan

Location

Related Publications (1)

• Kinoshita Y, Sakurai Y, Takabayashi N, Kudou K, Araki T, Miyagi T, Iwakiri K, Ashida K. Efficacy and Safety of Vonoprazan in Patients With Nonerosive Gastroesophageal Reflux Disease: A Randomized, Placebo-Controlled, Phase 3 Study. Clin Transl Gastroenterol. 2019 Nov;10(11):e00101. doi: 10.14309/ctg.0000000000000101.

  PMID: 31770139 DERIVED

MeSH Terms

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 4, 2016
• Study Start: November 15, 2016
• Primary Completion: February 25, 2018
• Study Completion: February 26, 2018
• Last Updated: August 2, 2019
• Results First Posted: August 2, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (30)