Healthy Volunteers
Conditions
Keywords
Vonoprazan, Gastroesophageal Reflux, Erosive Esophagitis
Brief summary
The primary objective of this study is to assess the bioavailability (BA) of a single oral dose of vonoprazan 20 mg sprinkle capsule, either sprinkled on pudding or on applesauce, relative to a vonoprazan 20 mg tablet in healthy participants.
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
Orally via tablet
Sponsors
Phathom Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* The participant is male or female 18 to 55 years of age, inclusive, at Screening. * The participant has a body mass index 18 to 32 kg/m\^2, inclusive, at Screening. * 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. * Male and female participants of reproductive potential must use an acceptable method of birth control (i.e., diaphragm with spermicide, intrauterine device, condom with foam or vaginal spermicide, oral contraceptives, or abstinence) from the signing of informed consent until 4 weeks after the last dose of study drug or be surgically sterile (i.e., vasectomy, hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for 12 consecutive months and documented plasma follicle stimulating hormone \[FSH\] level \>40 international unit (IU)/mL during Screening). * Female participants must have a negative pregnancy test at Screening and upon Check-in. * The participant agrees to comply with all protocol requirements. * The participant is able to provide written informed consent.
Exclusion criteria
* 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. * The participant has a positive test result for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening or Check-in. * The participant has a history of a clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality that may impact the ability of the participant to participate. * The participant has current or recent (within 6 months) gastrointestinal conditions that would be expected to influence the absorption of drugs (e.g., history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis \[EE\]), frequent (more than once per week) occurrence of heartburn, or any surgical intervention. * The participant has any other clinically significant findings on physical examination, clinical laboratory abnormalities, and/or ECG results that preclude his/her participation in the study, as deemed by the investigator. * The participant has used any prescription (excluding hormonal birth control) and/or over-the-counter medications (including CYP3A4 inducers) except acetaminophen (up to 2 g per day), 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 treatment period phase (ET) or end of study (EOS). * The participant has consumed grapefruit and/or grapefruit juice, Seville orange or Seville orange-containing products (eg, marmalade), or other food products that may be CYP3A4 inhibitors (eg, vegetables from the mustard green family \[kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard\] and charbroiled meats) within 7 days (or 5 half-lives) before the first dose of study drug and/or is expected to be unable to abstain through the study. * The participant has consumed caffeine- or xanthine-containing products within 48 hours (or 5 half-lives) before the first dose of study drug and/or is unable to abstain through the study. * The participant is a smoker and/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. * The participant has a history of alcohol abuse and/or drug addiction within the last year or excessive alcohol consumption (regular alcohol intake \>21 units per week for male participants and \>14 units of alcohol per week for female participants; 1 unit is equal to approximately 1/2 pint \[200 mL\] of beer, 1 small glass \[100 mL\] of wine, or 1 measure \[25 mL\] of spirits) or use of alcohol 48 hours before the first dose of study drug. * The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at Screening or Check-in. * The participant is involved in strenuous activity or contact sports within 24 hours before the first dose of study drug and during the study. * The participant has donated blood or blood products \>450 mL within 30 days before the first dose of study drug. * The participant has a history of relevant drug and/or food allergies (i.e., allergy to vonoprazan or excipients or any significant food allergy that could preclude a standard diet in the clinical unit). * The participant has received a study drug in another investigational study within 30 days of dosing. * Female participants who are pregnant or lactating; intend to become pregnant before, during, or within 4 weeks after participating in this study; or intend to donate ova during this time period. * The participant is not suitable for entry into the study in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
| Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
Secondary
| Measure | Time frame |
|---|---|
| Apparent Volume of Distribution (Vz/F) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
| Time to Maximum Observed Plasma Concentration (Tmax) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
| Terminal Elimination Rate Constant (λz) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
| Terminal Phase Half-life (t1/2) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
| Apparent Total Body Clearance (CL/F) of Vonoprazan | Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose. |
Countries
United States
Participant flow
Recruitment details
27 participants were randomized in a 1:1:1 ratio to 1 of 3 treatment sequences at 1 site in the United States.
Pre-assignment details
Screening assessments were conducted within 28 days before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Vonoprazan 20 mg: Treatment Sequence 1 Participants received vonoprazan 20 mg orally as a sprinkle capsule on 1 tablespoon of pudding on Day 1 of Treatment Period 1, orally as a sprinkle capsule on 1 tablespoon of applesauce on Day 1 of Treatment Period 2, and orally as a tablet on Day 1 of Treatment Period 3. Each treatment period was 3 days, with treatment received on Day 1 of each treatment period. There was a washout interval of a minimum of 7 days between study drug dosing in each period. | 9 |
| Vonoprazan 20 mg: Treatment Sequence 2 Participants received vonoprazan 20 mg orally as a tablet on Day 1 of Treatment Period 1, orally as a sprinkle capsule on 1 tablespoon of pudding on Day 1 of Treatment Period 2, and orally as a sprinkle capsule on 1 tablespoon of applesauce on Day 1 of Treatment Period 3. Each treatment period was 3 days, with treatment received on Day 1 of each treatment period. There was a washout interval of a minimum of 7 days between study drug dosing in each period. | 9 |
| Vonoprazan 20 mg: Treatment Sequence 3 Participants received vonoprazan 20 mg orally as a sprinkle capsule on 1 tablespoon of applesauce on Day 1 of Treatment Period 1, orally as a tablet on Day 1 of Treatment Period 2, and orally as a sprinkle capsule on 1 tablespoon of pudding on Day 1 of Treatment Period 3. Each treatment period was 3 days, with treatment received on Day 1 of each treatment period. There was a washout interval of a minimum of 7 days between study drug dosing in each period. | 9 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Vonoprazan 20 mg: Treatment Sequence 1 | Vonoprazan 20 mg: Treatment Sequence 2 | Vonoprazan 20 mg: Treatment Sequence 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 35.1 years STANDARD_DEVIATION 7.22 | 32.9 years STANDARD_DEVIATION 8.51 | 35.8 years STANDARD_DEVIATION 9.63 | 34.6 years STANDARD_DEVIATION 8.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 7 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 | 0 / 27 |
| other Total, other adverse events | 2 / 26 | 2 / 26 | 4 / 27 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 0 / 27 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the PK population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Vonoprazan | 238 ng•h/mL | Geometric Coefficient of Variation 43.2 |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Vonoprazan | 227 ng•h/mL | Geometric Coefficient of Variation 43.1 |
| Treatment C: Vonoprazan 20 mg Tablet | Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Vonoprazan | 231 ng•h/mL | Geometric Coefficient of Variation 44.4 |
90% CI: [97.25, 108.15]
90% CI: [92.55, 102.93]
Primary
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the pharmacokinetic (PK) population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Vonoprazan | 228 ng•h/mL | Geometric Coefficient of Variation 44.9 |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Vonoprazan | 216 ng•h/mL | Geometric Coefficient of Variation 46 |
| Treatment C: Vonoprazan 20 mg Tablet | Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Vonoprazan | 219 ng•h/mL | Geometric Coefficient of Variation 47.3 |
90% CI: [97.64, 109.41]
90% CI: [92.42, 103.56]
Primary
Maximum Observed Plasma Concentration (Cmax) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the PK population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Maximum Observed Plasma Concentration (Cmax) of Vonoprazan | 23.1 ng/mL | Geometric Coefficient of Variation 44.2 |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Maximum Observed Plasma Concentration (Cmax) of Vonoprazan | 22.4 ng/mL | Geometric Coefficient of Variation 41.9 |
| Treatment C: Vonoprazan 20 mg Tablet | Maximum Observed Plasma Concentration (Cmax) of Vonoprazan | 22.3 ng/mL | Geometric Coefficient of Variation 45.3 |
90% CI: [96.49, 112]
90% CI: [93.38, 108.39]
Secondary
Apparent Total Body Clearance (CL/F) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the PK population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Apparent Total Body Clearance (CL/F) of Vonoprazan | 83.9 litres/h | Geometric Coefficient of Variation 43.2 |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Apparent Total Body Clearance (CL/F) of Vonoprazan | 88.1 litres/h | Geometric Coefficient of Variation 43.1 |
| Treatment C: Vonoprazan 20 mg Tablet | Apparent Total Body Clearance (CL/F) of Vonoprazan | 86.6 litres/h | Geometric Coefficient of Variation 44.4 |
Secondary
Apparent Volume of Distribution (Vz/F) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the PK population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Apparent Volume of Distribution (Vz/F) of Vonoprazan | 908 litres | Geometric Coefficient of Variation 37.6 |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Apparent Volume of Distribution (Vz/F) of Vonoprazan | 915 litres | Geometric Coefficient of Variation 33.4 |
| Treatment C: Vonoprazan 20 mg Tablet | Apparent Volume of Distribution (Vz/F) of Vonoprazan | 911 litres | Geometric Coefficient of Variation 38.5 |
Secondary
Terminal Elimination Rate Constant (λz) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the PK population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Terminal Elimination Rate Constant (λz) of Vonoprazan | 0.0924 1/h | Geometric Coefficient of Variation 19.5 |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Terminal Elimination Rate Constant (λz) of Vonoprazan | 0.0963 1/h | Geometric Coefficient of Variation 18.4 |
| Treatment C: Vonoprazan 20 mg Tablet | Terminal Elimination Rate Constant (λz) of Vonoprazan | 0.0951 1/h | Geometric Coefficient of Variation 16 |
Secondary
Terminal Phase Half-life (t1/2) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the PK population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Terminal Phase Half-life (t1/2) of Vonoprazan | 7.50 hours | Geometric Coefficient of Variation 19.5 |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Terminal Phase Half-life (t1/2) of Vonoprazan | 7.20 hours | Geometric Coefficient of Variation 18.4 |
| Treatment C: Vonoprazan 20 mg Tablet | Terminal Phase Half-life (t1/2) of Vonoprazan | 7.29 hours | Geometric Coefficient of Variation 16 |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of Vonoprazan
Time frame: Day 1 of each 3-day Treatment Period: Within 0.25 hours pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose.
Population: Measured in the PK population, which included all participants who received at least 1 dose of vonoprazan and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. PK data are presented for each treatment received, as pre-specified.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: Vonoprazan 20 mg Sprinkle Capsule on Pudding | Time to Maximum Observed Plasma Concentration (Tmax) of Vonoprazan | 2.00 hours |
| Treatment B: Vonoprazan 20 mg Sprinkle Capsule on Applesauce | Time to Maximum Observed Plasma Concentration (Tmax) of Vonoprazan | 2.01 hours |
| Treatment C: Vonoprazan 20 mg Tablet | Time to Maximum Observed Plasma Concentration (Tmax) of Vonoprazan | 2.00 hours |