Bioequivalence Study of Esomeprazole 20 Milligram (mg) Delayed-Release Capsules in Healthy Adult Participants

A Randomized, Single Blind, Single Center, Single Dose, Two Period, Two Sequence Crossover Bioequivalence Study of Esomeprazole 20 mg Delayed-Release Capsules (Catalent, Guayama) Compared to the Esomeprazole 20 mg Delayed-Release Capsules ([Nexium 24HR] AstraZeneca Södertälje) in Healthy Adult Subjects Under Fasted Conditions

The purpose of this study is to evaluate bioequivalence parameters of esomeprazole capsules 20 mg (test product) vs. esomeprazole capsules 20 mg (reference product) under fasted conditions.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Diseases
• Intervention / Treatment: Drug: Esomeprazole 20 mg Delayed-Release Capsules; Drug: Esomeprazole 20 mg Delayed-Release Capsules (Nexium 24HR)

Detailed Description

This will be a single center, single dose, single-blind, randomized, two-sequence, two-period crossover, bioequivalence study in healthy adult participants with at least a 7-day washout period. The study will consist of an ambulant screening day within 28 days prior to first product administration and two study periods.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1P0A2
    • Syneos Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed.
• Participant who is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Healthy Participant, which is defined as in general good physical health, as judged by the investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead electrocardiogram (ECG) or clinical laboratory tests.
• Body Mass Index (BMI) of 18.5 to 30.0 Kilogram per square meter (kg/m^2); and a total body weight Greater than or equal to (>=) 50.0 kg for males and >=45.0 kg for females.
• Participant with two negative tests (one at screening within 72 hours of admission and one at check on Day-1) for active COVID-19, separated by Greater Than (>) 24 hours.
• Female participant of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment. Female participants who are not of childbearing potential must meet requirements in the Contraception section of protocol.

Exclusion Criteria:

• Participant who is an investigational site staff member directly involved in the conduct of the study and his/her family members, site staff member otherwise supervised by the investigator, or participant who is a GSK employee directly involved in the conduct of the study.
• Participation in other studies involving investigational drug(s) within 30 days prior to study entry and/or during study participation.
• Acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Pregnant female participant.
• Breastfeeding female participant.
• Known or suspected intolerance or hypersensitivity or photosensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
• Diagnosis of long QT syndrome or QTc > 450 Millisecond (msec) for males and > 470 msec for females.
• Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 Millimeter of mercury (mmHg), diastolic blood pressure lower than 50 or over 90 mmHg, or pulse rate less than 50 or over 100 beats per minute (bpm).
• A participant unwilling or unable to comply with Lifestyle Considerations described in this protocol.

• Use of any medication (including over-the-counter medications and herbal remedies) within 2 weeks before first scheduled study drug administration or within less than 10 times the elimination half-life of the respective drug (whichever is longer), or is anticipated to require any concomitant medication during that period or at any time throughout the study. Allowed treatments are:

  • systemic contraceptives and hormone replacement therapy, as long as female participant is on stable treatment for at least 3 months before first scheduled study drug administration and continues treatment throughout the study;
  • occasional use of acetaminophen (up to 2 g daily).
• Evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease within the last 5 years that may increase the risk associated with study participation.
• Clinically relevant chronic or acute infectious illnesses or febrile infections within two weeks prior to start of the study.
• Participant with signs and symptoms suggestive of COVID-19 (i.e. fever, cough, etc)* within 14 days of inpatient admission. *as defined by WHO or local guidance)
• Participant with known COVID-19 positive contacts in the past 14 days.
• Any vaccination, including COVID-19 vaccine, within 14 days prior to the first dose.

• Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance but not limited to any of the following:

  • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling or gastric banding (note: this is not applicable for minor abdominal surgery without significant tissue resection, e.g., appendectomy and herniorrhaphy);
  • History of inflammatory bowel disease;
  • History or current evidence of renal disease or impaired renal function at screening as indicated by abnormal levels of serum creatinine (> 123 micromole per liter [μmol/L] for males and > 95 μmol/L for females) or blood urea nitrogen (BUN) (>= 12.0 millimoles per liter [mmol/L]) or the presence of clinically significant abnormal urinary constituents (e.g. albuminuria);
  • History or current evidence of ongoing hepatic disease or impaired hepatic function at screening. A candidate will be excluded if more than one of the following lab value deviations are found: 1) aspartate transaminase (AST) (>= 1.2 upper limit of normal [ULN]), alanine transaminase [ALT] (>= 1.2 ULN), 2) gamma-glutamyl transpeptidase (GGT) (>= 1.2 ULN), alkaline phosphatase (ALP) (>= 1.2 ULN), 3) bilirubin (>= 48 μmol/L for males and >= 30 μmol/L for females) or creatine kinase (CK) (>= 3 ULN). A single deviation from the above values is acceptable and will not exclude the candidate, unless specifically advised by the investigator;
  • Evidence of urinary obstruction or difficulty in voiding at screening;
  • History or clinical evidence at screening of pancreatic injury or pancreatitis.
• Participant has a history of drug abuse or investigator has evidence of current drug abuse with drug classes that include but are not limited to barbiturates, tricyclic antidepressants, amphetamines, benzodiazepines, cocaine, opiates, cannabis or any other drugs (verified by urine drug screen or other reliable evidence).
• Evidence, as reported by an alcohol breath testing, for current alcohol abuse or reports a regular average alcohol consumption exceeding 18 g (women) or 35 g (men) of pure alcohol per day, i.e. 1 drink/day for women or 2 drinks/day for men (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of screening.
• Participant reported regular consumption of > 5 cups of coffee or tea per day (or equivalent consumption of >= 500 mg xanthine per day using other products)
• Smoker, defined as the use of tobacco or nicotine products during the 3 months prior to screening until admission to the unit or a positive urine cotinine test at screening.
• A participant who is unwilling to abstain from tobacco or nicotine-containing product use during the study.
• Participant reports consumption of any drug metabolizing enzyme (e.g. cytochrome P450 [CYP]3A4 or other cytochrome P450 enzymes) inducing or inhibiting aliments, beverages or food supplements (e.g. broccoli, Brussels sprouts, grapefruit, grapefruit juice, star fruit, St. John's Wort etc.) within 2 weeks prior to screening until admission to the unit.
• Positive results in any of the virology tests for human immunodeficiency virus (HIV) antigen and antibody, hepatitis C virus antibody (HCV Ab), hepatitis B surface antigen (HbsAg), and hepatitis B core antibody (HBcAb) ([immunoglobulin G] IgG + immunoglobulin M [IgM]).
• Performance of unaccustomed strenuous physical exercise (body building, high performance sports) from 2 weeks prior to admission and throughout the entire study.
• Allergy to skin disinfecting agents, tape, or latex rubber, whenever appropriate substitutions cannot be applied or in the investigator's opinion may pose a risk to the candidate.
• Any condition not identified in the protocol that in the opinion of the investigator would confound the evaluation and interpretation of the study data or may put the participant at risk
• Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 milliliter (mL) to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dose.
• Participant who has previously been enrolled in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Product/Reference Product; Participants will be randomly assigned to receive Esomeprazole 20 mg delayed-release one capsule once daily as oral administration on day 1 of period 1 and will receive Esomeprazole 20 mg delayed-release one capsule (Nexium 24HR) once daily as oral administration on day 1 of period 2. Participants are instructed to consume the entire amount of ambient temperature water (240 milliliter [mL]) along their investigational product. There will be washout period of 7 days between two treatment periods.	Drug: Esomeprazole 20 mg Delayed-Release Capsules; Esomeprazole 20 mg delayed-release capsules will be given as one capsule once daily as oral administration.; Drug: Esomeprazole 20 mg Delayed-Release Capsules (Nexium 24HR); Esomeprazole 20 mg delayed-release capsules (Nexium 24HR) will be given as one capsule once daily as oral administration.
Experimental: Reference Product/Test Products; Participants will be randomly assigned to receive Esomeprazole 20 mg delayed-release one capsule (Nexium 24HR) once daily as oral administration on day 1 of period 1 and will receive Esomeprazole 20 mg delayed-release one capsule once daily as oral administration on day 1 of period 2. Participants are instructed to consume the entire amount of ambient temperature water (240 milliliter [mL]) along their investigational product. There will be washout period of 7 days between two treatment periods.	Drug: Esomeprazole 20 mg Delayed-Release Capsules; Esomeprazole 20 mg delayed-release capsules will be given as one capsule once daily as oral administration.; Drug: Esomeprazole 20 mg Delayed-Release Capsules (Nexium 24HR); Esomeprazole 20 mg delayed-release capsules (Nexium 24HR) will be given as one capsule once daily as oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Post Dose Concentration (Cmax)	Cmax is defined as maximum observed post-dose concentration; obtained without interpolation. Blood samples were collected at the indicated time points for the analysis of Cmax. Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis.	Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days)
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to the Last Measurable Sampling Time Point	AUC(0-t) is defined as area under the plasma concentration versus time curve calculated from time 0 to the last measurable sampling time point t, computed using the linear trapezoidal rule. Blood samples were collected at the indicated time points for the analysis of AUC0-t. PK parameters were calculated by standard non-compartmental analysis.	Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to Infinity (AUC0-inf)	AUC(0-inf) is defined as area under the plasma concentration versus time curve calculated from time 0 to infinity. AUC0-inf is equal to (=) AUC0-t plus (+) concentration at the last measurable sampling time point [C(t)]/terminal elimination rate constant (λz). Blood samples were collected at the indicated time points for the analysis of AUC0-inf. PK parameters were calculated by standard non-compartmental analysis.	Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days)
Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex)	%AUCex is defined as percentage of AUC(0-inf) obtained by extrapolation, calculated as (1-[AUC{0-t}/AUC{0-inf}]) ×100. Blood samples were collected at the indicated time points for the analysis of %AUCex. PK parameters were calculated by standard non-compartmental analysis.	Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days)
Terminal Elimination Rate Constant	λz is defined as terminal elimination rate constant computed as the slope of the regression line of ln (C[t]) on time. The regression should generally involve at least 3 consecutive measurable concentrations that decrease over time. Blood samples were collected at the indicated time points for the analysis of λz. PK parameters were calculated by standard non-compartmental analysis.	Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days)
Time of the Maximum Observed Post-Dose Concentration (Tmax)	Tmax is defined as the time of the maximum observed post-dose concentration. Blood samples were collected at the indicated time points for the analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.	Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days)
Elimination Half-Life (T1/2)	T1/2 is defined as elimination half-life computed as T1/2 = ln(2)/ λz. Blood samples were collected at the indicated time points for the analysis of T1/2. PK parameters were calculated by standard non-compartmental analysis.	Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days)

Collaborators and Investigators

• Sponsor: HALEON

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Actual): June 2, 2022
• Study Completion (Actual): June 2, 2022

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: February 22, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): February 5, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: 218246

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No