A Study to Evaluate Vonoprazan Concentrations in Breast Milk of Healthy Lactating Women Receiving Vonoprazan 20 mg Once Daily or Vonoprazan 20 mg Twice Daily

A Phase 1, Open-label Study to Evaluate Vonoprazan Concentrations in Breast Milk of Healthy Lactating Women Receiving Vonoprazan 20 mg Once Daily or Vonoprazan 20 mg Twice Daily

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06391177

Enrollment

Registered

2024-04-30

Start date

2024-05-07

Completion date

2024-09-19

Last updated

2025-03-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Erosive Esophagitis, Heartburn, Helicobacter Pylori Infection, Symptomatic Nonerosive Gasroesophageal Reflux Disease

Keywords

Healthy participants, Helicobacter pylori infection, Erosive Esophagitis, Symptomatic nonerosive gasroesophageal reflux disease, Heartburn, Breast milk, Lactating women

Brief summary

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.

Interventions

DRUGVonoprazan

Oral tablet.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

1. The participant is a healthy lactating woman at least 18 years of age at the time of signing the informed consent form (ICF). 2. The participant has delivered a normal term infant (at least 37 weeks gestation) and has been breastfeeding or actively pumping breast milk for at least 4 weeks postpartum prior to the first dose. 3. The participant is willing to not breastfeed or otherwise use her breast milk during administration of vonoprazan and until at least 5 days after the last dose of the study drug. 4. The participant has confirmed that her breastfed infant is able to feed from a bottle. 5. The participant agrees to collect all breast milk from pre-dose to 24 hours after the morning dose administration on Day 4, using an electric pump. 6. The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at Screening. 7. Participants of childbearing potential must use an acceptable method of birth control (ie, diaphragm with spermicide, intrauterine device, condom with foam or vaginal spermicide, oral contraceptives, or abstinence) or be surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy). All participants must have a negative pregnancy test at Screening and before the first dose of study drug (Baseline). 8. The participant agrees to comply with all protocol requirements. 9. The participant is able to provide written informed consent.

Exclusion criteria

1. The participant has a positive pregnancy test at Screening or Baseline, is planning to become pregnant before, during, or within 4 weeks after participating in this study, or intends to donate ova during this time period, or is of childbearing potential and not using an effective contraceptive method. 2. The participant has a history of breast implants, breast augmentation, or breast reduction surgery that significantly impacts breastfeeding or collection of milk from one or both breasts. 3. The participant has signs or symptoms of mastitis or other condition that would prevent the collection of milk from one or both breasts. 4. The participant has undergone prior esophageal and/or gastrointestinal surgeries that may affect study drug absorption. 5. The participant has undergone surgery (other than cesarean section) within 30 days before the first dose of study drug. 6. The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at Screening. 7. The participant has any other clinically significant findings on physical examination, clinical laboratory abnormalities, or ECG results that preclude participation in the study, as deemed by the investigator. 8. The participant has used any prescription (excluding hormonal birth control) and/or over-the-counter medications (including cytochrome P450 3A4 inducers), including herbal or nutritional supplements, within 14 days before the first dose of study drug, and/or is expected to require any such medication during the course of the study until end of the Treatment Period. Use of multivitamins and acetaminophen (up to 2 g per day) is permissible. 9. The participant has consumed grapefruit and/or grapefruit juice, Seville orange, or Seville orange-containing products (eg, marmalade) within 7 days before the first dose of study drug and/or is expected to be unable to abstain through the study. 10. The participant is a smoker or has used nicotine or nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 6 months before the first dose of study drug. 11. The participant has a history of alcohol abuse or drug dependency within 12 months before the first dose of study drug. 12. The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at Screening, Baseline, or Day 4 (Check-in). 13. The participant is involved in strenuous activity or contact sports within 24 hours before the first dose of study drug and during the study. 14. The participant has a history of relevant drug and/or food allergies (ie, any significant food allergy that could preclude a standard diet in the clinical research unit). 15. The participant has received study drug in another investigational study (including vonoprazan) within 30 days prior to start of the Screening Period. 16. The participant has a history of hypersensitivity or allergies to vonoprazan or any of its formulation excipients (D-mannitol, microcrystalline cellulose, hydroxypropyl cellulose, fumaric acid, ascorbic acid, croscarmellose sodium, magnesium stearate, hypromellose, polyethylene glycol 8000, titanium dioxide, or ferric oxide red). 17. In the opinion of the investigator, the participant is not suitable for entry into the study.

Design outcomes

Primary

Measure	Time frame	Description
Time to Cmax (Tmax) of Vonoprazan in Breast Milk	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 maximum observed concentration (actual midpoint of the interval in which Cmax was observed).
Area Under Drug Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Following the Morning Dose of Vonoprazan in Breast Milk	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).	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.
Maximum Drug Concentration (Cmax) of Vonoprazan in Breast Milk	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 observed concentration after dosing.
Minimum Drug Concentration (Cmin) of Vonoprazan in Breast Milk	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 observed concentration after dosing.
Average Drug Concentration (Cavg) of Vonoprazan in Breast Milk	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 concentration, calculated as: AUC0-24/tau (tau=the difference between the end time of the last interval and dosing time).

Secondary

Measure	Time frame	Description
Percentage of Vonoprazan Excreted in Breast Milk Relative to the Total Dose Received	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).	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.
Estimated Infant Daily Dose 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).	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.
Estimated Relative Infant Dose to the Total Maternal Dose Received 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).	Percentage of daily infant dose relative to the daily maternal dose; calculated as (daily infant dose / daily maternal dose) \* 100.
Total Amount of Vonoprazan Excreted in Breast Milk	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).	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.

Countries

United States

Participant flow

Recruitment details

A total of 15 participants were enrolled in the United States between May 2024 and September 2024.

Pre-assignment details

Participants were administered vonoprazan once daily (QD) or twice daily (BID).

Participants by arm

Arm	Count
Vonoprazan 20 mg QD Participants were administered vonoprazan 20 mg QD for 4 consecutive days (Days 1 through 4).	5
Vonoprazan 20 mg BID Participants were administered vonoprazan 20 mg BID for 4 consecutive days (Days 1 through 4).	10
Total	15

Baseline characteristics

Characteristic	Vonoprazan 20 mg BID	Total	Vonoprazan 20 mg QD
Age, Continuous	29.7 years STANDARD_DEVIATION 3.71	31.3 years STANDARD_DEVIATION 4.45	34.4 years STANDARD_DEVIATION 4.45
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants	14 Participants	4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	1 Participants	1 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	8 Participants	12 Participants	4 Participants
Sex: Female, Male Female	10 Participants	15 Participants	5 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 10
other Total, other adverse events	1 / 5	4 / 10
serious Total, serious adverse events	0 / 5	0 / 10

Outcome results

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.