Clinical Trial Results:
A Phase 1, Randomized, Parallel-group, Open-label, Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Vonoprazan (10 or 20 mg Once Daily) in Adolescents With Symptomatic Gastroesophageal Reflux Disease
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Summary
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EudraCT number |
2023-000179-10 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
13 Jun 2023
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Results information
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Results version number |
v2(current) |
This version publication date |
23 Apr 2025
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First version publication date |
25 Dec 2023
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
VPED-102
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05343364 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Phathom Pharmaceuticals, Inc.
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Sponsor organisation address |
2150 East Lake Cook Road, Suite 800, Buffalo Grove, United States, IL 60089
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Public contact |
Phathom Medical Information, Phathom Pharmaceuticals, Inc., 1 888-775-7428, medicalinformation@phathompharma.com
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Scientific contact |
Phathom Medical Information, Phathom Pharmaceuticals, Inc., 1 888-775-7428, medicalinformation@phathompharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-002703-PIP01-19 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jun 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jun 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study is to evaluate the pharmacokinetic profile of vonoprazan in adolescent participants with symptomatic gastroesophageal reflux disease (GERD).
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Protection of trial subjects |
All aspects of the study were carefully monitored, by the sponsor or its designee, for compliance with applicable government regulation with respect to current good clinical practice and current standard operating procedures.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 May 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 24
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Worldwide total number of subjects |
24
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
24
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 24 participants were enrolled into this study in the United States between May 2022 and June 2023. | |||||||||||||||
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Pre-assignment
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Screening details |
The total duration of the study was up to 8 weeks. The Screening Period was up to 4 weeks, Treatment Period was 2 weeks, and safety follow-up phone call was 2 weeks after last study drug administration. | |||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Vonoprazan 10 mg QD | |||||||||||||||
Arm description |
Participants were randomized to receive vonoprazan 10 mg once daily (QD) from Day 1 to Day 14. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Vonoprazan
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Investigational medicinal product code |
TAK-438
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Oral tablet.
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Arm title
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Vonoprazan 20 mg QD | |||||||||||||||
Arm description |
Participants were randomized to receive vonoprazan 20 mg QD from Day 1 to Day 14. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Vonoprazan
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Investigational medicinal product code |
TAK-438
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Oral tablet.
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Baseline characteristics reporting groups
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Reporting group title |
Vonoprazan 10 mg QD
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Reporting group description |
Participants were randomized to receive vonoprazan 10 mg once daily (QD) from Day 1 to Day 14. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vonoprazan 20 mg QD
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Reporting group description |
Participants were randomized to receive vonoprazan 20 mg QD from Day 1 to Day 14. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Vonoprazan 10 mg QD
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Reporting group description |
Participants were randomized to receive vonoprazan 10 mg once daily (QD) from Day 1 to Day 14. | ||
Reporting group title |
Vonoprazan 20 mg QD
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Reporting group description |
Participants were randomized to receive vonoprazan 20 mg QD from Day 1 to Day 14. | ||
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End point title |
Maximum Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan [1] | ||||||||||||
End point description |
Plasma pharmacokinetic (PK) parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
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End point type |
Primary
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End point timeframe |
Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No additional statistical analyses were pre-specified for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Area Under the Plasma Concentration-time Curve During the Dosing Interval τ (AUCτ) of Vonoprazan [2] | ||||||||||||
End point description |
PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
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End point type |
Primary
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End point timeframe |
Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No additional statistical analyses were pre-specified for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Apparent Oral Clearance (CL/F) of Vonoprazan [3] | ||||||||||||
End point description |
PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
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End point type |
Primary
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End point timeframe |
Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No additional statistical analyses were pre-specified for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Apparent Central Volume of Distribution (Vc/F) of Vonoprazan [4] | ||||||||||||
End point description |
PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
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End point type |
Primary
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End point timeframe |
Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No additional statistical analyses were pre-specified for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants Experiencing Adverse Events (AEs) | ||||||||||||||||||||||||||||||
End point description |
AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug. Treatment-emergent adverse event (TEAE): any AE that occurred after the first dose of study drug or at baseline that worsens in either intensity or frequency after the first dose of study drug. Serious AE: any AE for which the following occurred: death, was life threatening, hopsitalization or prolongation of hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or the AE was deemed an important medical event. Related AE: any AE that follows a reasonable temporal sequence from administration of study drug, or for which possible involvement of the drug cannot be ruled out, although factors other than the study drug may also be responsible. Clinically significant changes from baseline in laboratory test values, (hematology, serum chemistry and urinalysis), electrocardiograms (ECG) and vital signs were reported as AEs.
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End point type |
Secondary
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End point timeframe |
Up to Day 28
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| Notes [5] - Safety Set: inclusive of all participants who received at least 1 dose of study drug. [6] - Safety Set: inclusive of all participants who received at least 1 dose of study drug. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to Day 28
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Adverse event reporting additional description |
Safety Set: inclusive of all participants who received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Vonoprazan 20 mg QD
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Reporting group description |
Participants were randomized to receive vonoprazan 20 mg QD from Day 1 to Day 14. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vonoprazan 10 mg QD
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Reporting group description |
Participants were randomized to receive vonoprazan 10 mg QD from Day 1 to Day 14. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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11 Apr 2022 |
Reasons for amendment:
- To clarify that participants must be aged 12 to 17 years, inclusive, at time of informed consent and throughout study participation.
- To clarify that only select sites will perform gastric pH monitoring in participants deemed clinically indicated by the principal investigator.
- To add that all study drug doses be taken on an empty stomach.
- To add that the time and content of any meals consumed prior to taking study drug on Day 6 or Day 7 be recorded.
- To add details for Day 7 dosing with respect to allowed water and meals.
- To clarify that Day -1 assessments are only required for participants undergoing gastric pH monitoring.
- To clarify that Day 6 is an optional visit for participants that check in to the clinic in the evening before starting Day 7 assessments.
- Remove the Day 14 PK blood collection.
- Remove morphology from electrocardiogram assessments. |
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14 Sep 2022 |
Reasons for amendment:
- Increased number of sites from 5 to 12.
- Updated information about vonoprazan.
- Removed duplicate entry for sucralfate under excluded medications and treatments.
- Removed gastrin and pepsinogen I and II assessments.
- Removed optional Day 6 visit.
- Modified strategy to estimate PK parameters to a population based approach; as a result adjusted PK sampling schedule on Day 7, added PK sampling on Day 14, provided information on when time of dosing and meals should be collected and remove Tmax,ss and t1/2z PK parameters.
- Removed required overnight stay for PK sampling due to revised sampling schedule.
- Added details to the 24-hour gastric pH monitoring.
- Moved symptom assessments from Day 8 to Day 7.
- Updated Schedule of Events and Study Design to reflect above changes. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
