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

NCT04729101 | Completed Phase 1 Results FDA Drug

• 1 other identifier: VONO-103
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Healthy Participants

Keywords

Vonoprazan; Lansoprazole

Outcome Measures

Primary Outcomes (9)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Treatment A (vonoprazan)

EXPERIMENTAL

Participants will be randomized to receive vonoprazan (treatment A) and lansoprazole (treatment B) in a two period sequence, following either treatment sequence AB or BA. There will be a washout period of at least 7 days between Period 1 and Period 2. Vonoprazan will be administered via 20 mg oral tablet once daily on Day 1 through to Day 7 in a period, where each period is up to 8 days.

Drug: Vonoprazan

Treatment B (lansoprazole)

ACTIVE COMPARATOR

Participants will be randomized to receive vonoprazan (treatment A) and lansoprazole (treatment B) in a two period sequence, following either treatment sequence AB or BA. There will be a washout period of at least 7 days between Period 1 and Period 2. Lansoprazole will be administered via 30 mg oral capsule once daily on Day 1 through to Day 7 in a period, where each period is up to 8 days.

Drug: Lansoprazole

Interventions

Vonoprazan DRUG

Oral tablet

Treatment A (vonoprazan)

Lansoprazole DRUG

Oral capsule

Treatment B (lansoprazole)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, male or female 18 - 55 years of age, inclusive, at screening.
• 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.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m\^2 at screening.
• 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.
• 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).
• 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.
• 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.

You may not qualify if:

• Participants must not be enrolled in the study if they meet any of the following criteria:
• 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.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the principal investigator (PI) or designee.
• 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.
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s), its excipients, related compounds, or lidocaine.
• 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).
• Positive result for H. pylori breath test at screening.
• Had diarrhea or vomiting within 48 hours prior to check-in.
• Has nasal abnormalities that could affect pH probe insertion.
• Cannot tolerate placement of the pH probe.
• Female participants with a positive pregnancy test at screening or check-in or who are lactating.
• Positive urine drug or alcohol results at screening or check-in.
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.

Sponsors & Collaborators

• Phathom Pharmaceuticals, Inc.: lead

Study Sites (1)

Celerion, 2420 W Baseline Rd,

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• Laine L, Sharma P, Mulford DJ, Hunt B, Leifke E, Smith N, Howden CW. Pharmacodynamics and Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan and the Proton Pump Inhibitor Lansoprazole in US Subjects. Am J Gastroenterol. 2022 Jul 1;117(7):1158-1161. doi: 10.14309/ajg.0000000000001735. Epub 2022 Mar 16.

  PMID: 35294415 DERIVED

MeSH Terms

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; Lansoprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Phathom Medical Information
• Organization: Phathom Pharmaceuticals, Inc.

medicalinformation@phathompharma.com

1-888-775-PHAT (7428)

Study Officials

• Medical Director

  Phathom Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 28, 2021
• Study Start: January 28, 2021
• Primary Completion: June 12, 2021
• Study Completion: June 26, 2021
• Last Updated: March 31, 2023
• Results First Posted: March 31, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)