Gastroesophageal Reflux
Conditions
Keywords
Vonoprazan, Gastroesophageal Reflux, GERD, Adolescents, Pharmacokinetics
Brief summary
The primary objective of this study is to evaluate the pharmacokinetic profile of vonoprazan in adolescent participants with symptomatic gastroesophageal reflux disease (GERD).
Detailed description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Interventions
DRUGVonoprazan
Oral Tablet
Sponsors
Phathom Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* The participant is 12 to 17 years of age, inclusive, at the time of informed consent signing and throughout study participation. * The participant has a body weight within the 5th through 95th percentile by age, inclusive, as determined by the National Center for Health Statistics. * The participant has a medical history of symptoms of GERD for at least 3 months prior to screening, based on physical examination, current symptoms (eg, heartburn), or diagnostic tests (eg, pH or endoscopy). Notes in the medical records and/or other source documents such as prior endoscopies can be used to support the diagnosis. * The participant has symptoms of at least moderate heartburn severity based on the GERD Symptom Assessment-Investigator scale performed at screening. * The participant must be able to swallow study drug. * Parent or legal guardian (ie, legally authorized representative \[LAR\]) is willing and able to complete the informed consent process and comply with study procedures and visit schedule. The participant will provide assent as applicable. * A female participant of childbearing potential who is or may be sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from the signing of informed consent until 2 weeks after the last dose of study drug.
Exclusion criteria
* The participant has used prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) within 7 days prior to randomization or requires their use during the Treatment Period. * The participant has used sucralfate or antacids within 1 day prior to randomization or requires their use during the Treatment Period. * The participant has received other agents affecting digestive organs, including muscarinic antagonists (eg, hyoscyamine), prokinetics, oral anticholinergic agents, prostaglandins, bismuth from 30 days prior to Day 1 or requires their use during the course of the study. * The participant has received atazanavir sulfate or rilpivirine hydrochloride from 5 days prior to Day 1 or requires their use during the course of the study. * The participant has received any investigational compound (including vonoprazan) within 30 days prior to the start of the Screening Period. * The participant is an immediate family member or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, child, sibling) or who may have consented under duress. * The participant requires hospitalization or has surgery scheduled during the course of the study or has undergone major surgical procedures within 30 days prior to the Screening Period. * The participant has undergone prior gastrointestinal surgeries such as fundoplication. * The participant has any abnormal laboratory test values at the start of the Screening Period. * The participant has a history of hypersensitivity or allergies to vonoprazan (including the formulation excipients: D-mannitol, microcrystalline cellulose, hydroxypropyl cellulose, fumaric acid, croscarmellose sodium, magnesium stearate, hypromellose, macrogol 8000, and titanium oxide, or red or yellow ferric oxide). * The participant used any prescription (excluding hormonal birth control) or over-the-counter medications (including CYP3A4 inducers), including herbal or nutritional supplements, within 14 days (or 5 half-lives) before the first dose of study drug or throughout the study. NOTE: Acid suppressive therapies are considered separately under
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan | 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 | 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. |
| Area Under the Plasma Concentration-time Curve During the Dosing Interval τ (AUCτ) of Vonoprazan | 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 | 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. |
| Apparent Oral Clearance (CL/F) of Vonoprazan | 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 | 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. |
| Apparent Central Volume of Distribution (Vc/F) of Vonoprazan | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) | Up to Day 28 | 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 and vital signs were reported as AEs. |
Countries
United States
Participant flow
Recruitment details
A total of 24 participants were enrolled into this study in the United States between May 2022 and June 2023.
Pre-assignment 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.
Participants by arm
| Arm | Count |
|---|---|
| Vonoprazan 10 mg QD Participants were randomized to receive vonoprazan 10 mg QD from Day 1 to Day 14. | 12 |
| Vonoprazan 20 mg QD Participants were randomized to receive vonoprazan 20 mg QD from Day 1 to Day 14. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Miscellaneous | 0 | 1 |
Baseline characteristics
| Characteristic | Vonoprazan 20 mg QD | Total | Vonoprazan 10 mg QD |
|---|---|---|---|
| Age, Continuous | 15.2 years STANDARD_DEVIATION 1.75 | 14.8 years STANDARD_DEVIATION 1.78 | 14.3 years STANDARD_DEVIATION 1.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 16 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 16 Participants | 9 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Apparent Central Volume of Distribution (Vc/F) of Vonoprazan
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.
Time frame: 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
Population: PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vonoprazan 10 mg QD | Apparent Central Volume of Distribution (Vc/F) of Vonoprazan | 686 liters |
| Vonoprazan 20 mg QD | Apparent Central Volume of Distribution (Vc/F) of Vonoprazan | 704 liters |
Primary
Apparent Oral Clearance (CL/F) of Vonoprazan
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.
Time frame: 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
Population: PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vonoprazan 10 mg QD | Apparent Oral Clearance (CL/F) of Vonoprazan | 124 L/h |
| Vonoprazan 20 mg QD | Apparent Oral Clearance (CL/F) of Vonoprazan | 117 L/h |
Primary
Area Under the Plasma Concentration-time Curve During the Dosing Interval τ (AUCτ) of Vonoprazan
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.
Time frame: 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
Population: PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vonoprazan 10 mg QD | Area Under the Plasma Concentration-time Curve During the Dosing Interval τ (AUCτ) of Vonoprazan | 94.6 h*ng/mL |
| Vonoprazan 20 mg QD | Area Under the Plasma Concentration-time Curve During the Dosing Interval τ (AUCτ) of Vonoprazan | 208 h*ng/mL |
Primary
Maximum Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan
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.
Time frame: 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
Population: PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vonoprazan 10 mg QD | Maximum Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan | 13.4 ng/mL |
| Vonoprazan 20 mg QD | Maximum Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan | 26.7 ng/mL |
Secondary
Number of Participants Experiencing Adverse Events (AEs)
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 and vital signs were reported as AEs.
Time frame: Up to Day 28
Population: Safety Set: inclusive of all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vonoprazan 10 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any Serious Study Drug-related TEAEs | 0 Participants |
| Vonoprazan 10 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any TEAE Leading to Treatment Discontinuation | 0 Participants |
| Vonoprazan 10 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any TEAEs | 4 Participants |
| Vonoprazan 10 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any TEAE Leading to Study Discontinuation | 0 Participants |
| Vonoprazan 10 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any Study Drug-related TEAEs | 0 Participants |
| Vonoprazan 10 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any AEs Leading to Death | 0 Participants |
| Vonoprazan 10 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any Serious TEAEs | 0 Participants |
| Vonoprazan 20 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any AEs Leading to Death | 0 Participants |
| Vonoprazan 20 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any TEAEs | 1 Participants |
| Vonoprazan 20 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any Serious TEAEs | 0 Participants |
| Vonoprazan 20 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any Study Drug-related TEAEs | 0 Participants |
| Vonoprazan 20 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any TEAE Leading to Treatment Discontinuation | 0 Participants |
| Vonoprazan 20 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any TEAE Leading to Study Discontinuation | 0 Participants |
| Vonoprazan 20 mg QD | Number of Participants Experiencing Adverse Events (AEs) | Any Serious Study Drug-related TEAEs | 0 Participants |