Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Vonoprazan and Lansoprazole in Healthy Participants

Healthy Participants Clinical Trial

Official title:

A Phase 1, Open-Label, Randomized, Crossover Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Vonoprazan (20 mg) and Lansoprazole (30 mg) in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04729101
• Other study ID #: VONO-103
• Status: Completed
• Phase: Phase 1
• Start date: January 28, 2021
• Est. completion date: June 26, 2021

Study information

• Verified date: June 2022
• Source: Phathom Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: June 26, 2021
• Est. primary completion date: June 12, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Vonoprazan
Oral tablet
• Lansoprazole
Oral capsule

Locations

Country	Name	City	State
United States	Celerion, 2420 W Baseline Rd,	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Phathom Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gastric pH >4 Holding Time Ratio (HTR): Percentage of Time Gastric pH Was Above 4 Over a 24-hour Monitoring Period Following Study Drug Administration	Calculated as: Time pH >4*100/total actual monitoring period time. Gastric pH was measured continuously over a 24-hour period on Days 1 and 7 of Periods 1 and 2, using a pH and pressure sensitive probe and ambulatory pH recording system. A pH recording was taken every second.	Day 1 and Day 7 of each treatment period
Primary	Mean Gastric pH Over a 24-hour Monitoring Period Following Study Drug Administration (pH0-24)	The average gastric pH was a measure of the immediate effect on gastric pH and the duration of effect on gastric pH. Gastric pH was measured continuously over a 24-hour period on Days 1 and 7 of Periods 1 and 2, using a pH and pressure sensitive probe and ambulatory pH recording system. A pH recording was taken every second. The pH scale ranges from 0 to 14 with values below 7 being more acidic and values above 7 being more basic. Normal gastric pH is between 1.5 and 3.5.	Day 1 and Day 7 of each treatment period
Primary	Area Under the Concentration-Time Curve From Time 0 to the 24-Hour Time Point (AUC0-24)	Calculated using the Linear Trapezoidal with Linear Interpolation Method. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.	Day 1: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 9, 10, 12, 13, 16, and 24 hours postdose
Primary	Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf)	Calculated as the area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) + (Clast/Kel) where Clast is the last observed/measured concentration and Kel is the apparent first-order terminal elimination rate constant. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.	Day 1: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 9, 10, 12, 13, 16, and 24 hours postdose
Primary	Maximum Observed Plasma Concentration (Cmax)	Cmax was taken directly from bioanalytical data. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.	Day 1: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 9, 10, 12, 13, 16, and 24 hours postdose
Primary	Time to Reach Cmax (Tmax)	Taken from the clinical database as the difference in the time of administration and the time of the blood draw which was associated with the Cmax. If the maximum value occurred at more than one time point, Tmax was defined as the first time point with this value. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.	Day 1: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 9, 10, 12, 13, 16, and 24 hours postdose
Primary	Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) at Steady State (ss)	Calculated using the Linear Trapezoidal with Linear Interpolation Method. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.	Day 7: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 9, 10, 12, 13, 16, and 24 hours postdose
Primary	Cmax at Steady State (Cmax,ss)	Cmax,ss was taken directly from bioanalytical data. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.	Day 7: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 9, 10, 12, 13, 16, and 24 hours postdose
Primary	Tmax at Steady State (Tmax,ss)	Taken from the clinical database as the difference in the time of administration and the time of the blood draw which was associated with the Cmax,ss. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.	Day 7: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 9, 10, 12, 13, 16, and 24 hours postdose