Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Vonoprazan and Lansoprazole in Healthy Participants
Condition: Healthy Participants
Intervention: Vonoprazan; Lansoprazole
Intervention description: Oral tablet; Oral capsule
Intervention MeSH terms: Lansoprazole; Dexlansoprazole
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Vonoprazan; Lansoprazole

Summary:

      To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of vonoprazan (20 mg) and
      lansoprazole (30 mg) following single (Day 1) and multiple doses (Day 7).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must fulfill all the following inclusion criteria to be eligible for
             participation in the study:

               1. Healthy, adult, male or female 18 - 55 years of age, inclusive, at screening.

               2. Continuous nonsmoker who has not used nicotine-containing products for at least 3
                  months prior to the first dosing and throughout the study, based on participant
                  self-reporting.

               3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m^2 at screening.

               4. Medically healthy with no clinically significant medical history, physical
                  examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as
                  deemed by the principal investigator (PI) or designee.

               5. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine
                  aminotransferase (ALT), and gamma-glutamyl transferase (GGT) < upper limits of
                  the clinical laboratory reference range (one recheck is permissible).

               6. A female of childbearing potential is either sexually inactive (abstinent as a
                  life style) for 28 days prior to the first dosing and throughout the study or is
                  using one of the following acceptable birth control methods:

                    -  hormonal oral contraceptives, vaginal ring, transdermal patch, or hormone
                       releasing intrauterine device for at least 3 months prior to the first
                       dosing and with either a physical (e.g., condom, diaphragm, or other) or a
                       chemical (e.g., spermicide) barrier method from the time of screening and
                       throughout the study.

                    -  Depot/implantable hormone (e.g., Depo-Provera®, Implanon®) for at least 3
                       months prior to the first dosing and throughout the study.

                  In addition, female participants of childbearing potential will be advised to
                  remain sexually inactive or to keep the same birth control method for at least 28
                  days after the last dose.

               7. A female of non-childbearing potential has undergone one of the following
                  sterilization procedures at least 6 months prior to the first dosing:

                    -  hysteroscopic sterilization;

                    -  bilateral tubal ligation or bilateral salpingectomy;

                    -  hysterectomy;

                    -  bilateral oophorectomy;

                  or be postmenopausal with amenorrhea for at least 1 year prior to the first
                  dosing and follicle stimulating hormone (FSH) serum levels consistent with
                  postmenopausal status.

               8. A non-vasectomized, male participant must agree to use a condom with spermicide
                  or abstain from sexual intercourse during the study until 90 days after the last
                  dosing. (No restrictions are required for a vasectomized male provided his
                  vasectomy has been performed 4 months or more prior to the first dosing. A male
                  who has been vasectomized less than 4 months prior to study first dosing must
                  follow the same restrictions as a non-vasectomized male).

               9. If male, must agree not to donate sperm from the first dosing until 90 days after
                  the last dosing.

              10. Understands the study procedures in the informed consent form (ICF), and be
                  willing and able to comply with the protocol.

        Exclusion Criteria:

          -  Participants must not be enrolled in the study if they meet any of the following
             criteria:

               1. Is mentally or legally incapacitated or has significant emotional problems at the
                  time of the screening visit or expected during the conduct of the study.

               2. History or presence of clinically significant medical or psychiatric condition or
                  disease in the opinion of the principal investigator (PI) or designee.

               3. History of any illness that, in the opinion of the PI or designee, might confound
                  the results of the study or poses an additional risk to the participant by their
                  participation in the study.

               4. History or presence of alcohol or drug abuse within the past 2 years prior to the
                  first dosing.

               5. History or presence of hypersensitivity or idiosyncratic reaction to the study
                  drug(s), its excipients, related compounds, or lidocaine.

               6. Clinically significant gastrointestinal (GI) disorder (e.g., gastric ulcer (GU),
                  Gastroesophageal reflux disease (GERD), impaction, chronic constipation,
                  inflammatory bowel disease, ischemic colitis, vascular intestinal
                  atherosclerosis, previous bowel resection, bowel obstruction, bariatric surgery,
                  cholecystitis [including history of cholecystectomy], and/or appendectomy).

               7. Positive result for H. pylori breath test at screening.

               8. Had diarrhea or vomiting within 48 hours prior to check-in.

               9. Has nasal abnormalities that could affect pH probe insertion.

              10. Cannot tolerate placement of the pH probe.

              11. Female participants with a positive pregnancy test at screening or check-in or
                  who are lactating.

              12. Positive urine drug or alcohol results at screening or check-in.

              13. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B
                  surface antigen (HBsAg), or hepatitis C virus (HCV).

              14. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at
                  screening.

              15. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.

              16. Fridericia's correction to the QT interval (QTcF) interval is >460 msec (males)
                  or >470 msec (females) or has electrocardiogram (ECG) findings deemed abnormal
                  with clinical significance by the PI or designee at screening.

              17. Estimated creatinine clearance <80 mL/min at screening.

              18. The participant has serum creatinine >1.22 mg/dL at screening or check-in.

              19. Unable to refrain from or anticipates the use of:

                    -  Any drug, including prescription and non-prescription medications, herbal
                       remedies, or vitamin supplements beginning 14 days prior to the first dosing
                       and throughout the study. Medication listed as part of acceptable birth
                       control methods will be allowed. After randomization, acetaminophen (up to 2
                       g per 24 hours) may be administered at the discretion of the PI or designee.
                       Topical lidocaine may be administered for pH probe insertion. Hormone
                       replacement therapy will also be allowed.

                    -  Any drugs known to be significant inducers of CYP3A4/5, CYP1A2, and/or
                       CYP2C19 for 28 days prior to the first dosing and throughout the study.
                       Appropriate sources will be consulted by the PI or designee to confirm lack
                       of PK / PD interaction with study drug.

              20. Has been on a diet incompatible with the on-study diet, in the opinion of the PI
                  or designee, within the 30 days prior to the first dosing and throughout the
                  study.

              21. Donation of blood or significant blood loss within 56 days prior to the first
                  dosing.

              22. Plasma donation within 7 days prior to the first dosing.

              23. Participation in another clinical study within 30 days prior to the first dosing.
                  The 30 day window will be derived from the date of the last blood collection or
                  dosing, whichever is later, in the previous study to Day 1 of Period 1 of the
                  current study.