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The primary objective is to determine the pharmacokinetics (PK) of vonoprazan in breast milk of healthy lactating women who have received vonoprazan administered once daily or vonoprazan 20 mg administered twice daily for 4 consecutive days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vonoprazan 20 mg Once Daily | Experimental | Participants will be administered once-daily doses of vonoprazan 20 mg for 4 consecutive days (Days 1 through 4). |
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| Vonoprazan 20 mg Twice Daily | Experimental | Participants will be administered twice-daily doses of vonoprazan 20 mg for 4 consecutive days (Days 1 through 4). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vonoprazan | Drug | Oral tablet. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under Drug Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Following the Morning Dose of Vonoprazan in Breast Milk | AUC from time 0 to 24 hours post-dose, calculated as: the sum of the product of the concentration of the interval and the width of the interval. | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| Maximum Drug Concentration (Cmax) of Vonoprazan in Breast Milk | Maximum observed concentration after dosing. | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| Minimum Drug Concentration (Cmin) of Vonoprazan in Breast Milk | Minimum observed concentration after dosing. | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| Average Drug Concentration (Cavg) of Vonoprazan in Breast Milk | Average concentration, calculated as: AUC0-24/tau (tau=the difference between the end time of the last interval and dosing time). | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| Time to Cmax (Tmax) of Vonoprazan in Breast Milk | Time to maximum observed concentration (actual midpoint of the interval in which Cmax was observed). | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| Measure | Description | Time Frame |
|---|---|---|
| Total Amount of Vonoprazan Excreted in Breast Milk | Total amount of drug excreted in breast milk over 24 hours; calculated as the sum of drug concentration × expressed milk volume in each collection interval over 24-hour period. | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PPD Development, LP | Las Vegas | Nevada | 89113 | United States |
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Participants were administered vonoprazan once daily (QD) or twice daily (BID).
A total of 15 participants were enrolled in the United States between May 2024 and September 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vonoprazan 20 mg QD | Participants were administered vonoprazan 20 mg QD for 4 consecutive days (Days 1 through 4). |
| FG001 | Vonoprazan 20 mg BID | Participants were administered vonoprazan 20 mg BID for 4 consecutive days (Days 1 through 4). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 18, 2024 | Mar 3, 2025 |
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| Percentage of Vonoprazan Excreted in Breast Milk Relative to the Total Dose Received | Total amount of drug excreted over 24 hours relative to total dose administered; calculated as the sum of (total amount of drug excreted in each collection interval / total dose received over 24-hour period) * 100. | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| Estimated Infant Daily Dose of Vonoprazan | Estimated weight adjusted daily dose consumed by the infant through breast milk; calculated as total amount of drug excreted over 24-hour period / weight of infant. Calculation used the nominal infant weight of 6.0 kg which is the approximate 50th percentile for a 3-month old infant. | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| Estimated Relative Infant Dose to the Total Maternal Dose Received of Vonoprazan | Percentage of daily infant dose relative to the daily maternal dose; calculated as (daily infant dose / daily maternal dose) * 100. | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
| COMPLETED |
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| NOT COMPLETED |
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Safety population: included all participants who received at least 1 dose of the study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Vonoprazan 20 mg QD | Participants were administered vonoprazan 20 mg QD for 4 consecutive days (Days 1 through 4). |
| BG001 | Vonoprazan 20 mg BID | Participants were administered vonoprazan 20 mg BID for 4 consecutive days (Days 1 through 4). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under Drug Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Following the Morning Dose of Vonoprazan in Breast Milk | AUC from time 0 to 24 hours post-dose, calculated as: the sum of the product of the concentration of the interval and the width of the interval. | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | ng•h/mL | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Primary | Maximum Drug Concentration (Cmax) of Vonoprazan in Breast Milk | Maximum observed concentration after dosing. | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Primary | Minimum Drug Concentration (Cmin) of Vonoprazan in Breast Milk | Minimum observed concentration after dosing. | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Primary | Average Drug Concentration (Cavg) of Vonoprazan in Breast Milk | Average concentration, calculated as: AUC0-24/tau (tau=the difference between the end time of the last interval and dosing time). | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Primary | Time to Cmax (Tmax) of Vonoprazan in Breast Milk | Time to maximum observed concentration (actual midpoint of the interval in which Cmax was observed). | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Median | Full Range | hours | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Secondary | Total Amount of Vonoprazan Excreted in Breast Milk | Total amount of drug excreted in breast milk over 24 hours; calculated as the sum of drug concentration × expressed milk volume in each collection interval over 24-hour period. | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | mg | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Secondary | Percentage of Vonoprazan Excreted in Breast Milk Relative to the Total Dose Received | Total amount of drug excreted over 24 hours relative to total dose administered; calculated as the sum of (total amount of drug excreted in each collection interval / total dose received over 24-hour period) * 100. | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | percentage of vonoprazan | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Secondary | Estimated Infant Daily Dose of Vonoprazan | Estimated weight adjusted daily dose consumed by the infant through breast milk; calculated as total amount of drug excreted over 24-hour period / weight of infant. Calculation used the nominal infant weight of 6.0 kg which is the approximate 50th percentile for a 3-month old infant. | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | mg/kg/day | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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| Secondary | Estimated Relative Infant Dose to the Total Maternal Dose Received of Vonoprazan | Percentage of daily infant dose relative to the daily maternal dose; calculated as (daily infant dose / daily maternal dose) * 100. | PK population: included all participants who received sufficient doses of vonoprazan and had sufficient concentration data in milk to support accurate estimation of at least 1 PK parameter in milk. | Posted | Mean | Standard Deviation | percentage of total maternal dose | Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours). |
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Day 1 up to Day 11
A treatment emergent adverse event (TEAE) was defined as any event that occurred after the first dose of the study drug or any event at Baseline that worsened in either intensity or frequency after the first dose of the study drug until 30 days after the last dose of the study drug.
Safety population: included all participants who received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vonoprazan 20 mg QD | Participants were administered vonoprazan 20 mg QD for 4 consecutive days (Days 1 through 4). | 0 | 5 | 0 | 5 | 1 | 5 |
| EG001 | Vonoprazan 20 mg BID | Participants were administered vonoprazan 20 mg BID for 4 consecutive days (Days 1 through 4). | 0 | 10 | 0 | 10 | 4 | 10 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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Principal investigators (PIs) are not permitted to publish the data. Data may be considered for reporting at a scientific meeting or for publication in a scientific journal. In these cases, the sponsor will be responsible for these activities and will work with the PIs to determine how the manuscript is written and edited, the number and order of authors, the publication to which it will be submitted, and any other related issues. The sponsor has final approval authority over all such issues.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Phathom Medical Information | Phathom Pharmaceuticals, Inc. | 1-888-775-7428 | medicalinformation@phathompharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2024 | Mar 4, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006356 | Heartburn |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C552956 | 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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