BE Study Between a Capsule and a Sachet Formulation of D961H by Pharmacodynamics in Japanese Healthy Male Subjects

An Open Label, Randomised, Single Center, 2 Way Crossover Study to Assess Bioequivalence Between a Commercial HPMC Capsule of D961H 20 mg and a Pellets Based Sachet Formulation of D961H 20 mg by Pharmacodynamics (Intragastric pH) After Once-daily Repeated Oral Administration in Japanese Healthy Male Subjects

The purpose of this study is; To investigate whether a D961H sachet 20 mg is bioequivalent to a D961H HPMC capsule 20 mg by the assessment of percentage of time with intragastric pH>4.

To compare a D961H sachet 20 mg with a D961H HPMC capsule 20 mg by the assessment of percentage of time with intragastric pH>3 during 24 hours and 24-hour median pH.

To compare PK properties of a D961H sachet 20 mg with those of D961H HPMC capsule 20 mg.

To evaluate the safety and tolerability of a D961H sachet 20 mg and D961H HPMC capsule 20 mg.

Study Overview

• Status: Completed
• Conditions: Gastric Ulcer; Duodenal Ulcer; Reflux Esophagitis; Anastomotic Ulcer; Etc.
• Intervention / Treatment: Drug: D961H sachet 20 mg; Drug: D961H HPMC capsule 20 mg

Detailed Description

The purpose of this study is; To investigate whether a pellets based sachet formulation of D961H 20 mg (D961H sachet 20 mg) is bioequivalent to a commercial HPMC capsule of D961H 20 mg (D961H HPMC capsule 20 mg) after repeated oral doses by the assessment of percentage of time with intragastric pH>4 during 24 hours after dose on Day 5.

To compare a D961H sachet 20 mg with a D961H HPMC capsule 20 mg after repeated oral doses by the assessment of percentage of time with intragastric pH>3 during 24 hours and 24-hour median pH after dose on Day 5

To compare PK properties of a D961H sachet 20 mg with those of D961H HPMC capsule 20 mg after repeated oral doses by the assessment of AUCτ, Cmax,ss, AUC0-t,ss, MRT, tmax,ss, and t1/2,ss of esomeprazole after dose on Day 5.

To evaluate the safety and tolerability of a D961H sachet 20 mg and D961H HPMC capsule 20 mg by the assessment of adverse events, clinical laboratory tests, blood pressure (BP), pulse rate and body temperature.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-0025
    • Hakata Clinic Medical Co. LTA
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures
• Healthy Japanese male subjects between 20 and 45 years of age
• Body Mass Index (BMI=weight/height2) 19-27 (kg/m2)
• Body weight 50-85 kg
• Negative for HIV antigen/antibody, Hepatitis B surface antigen, Hepatitis C antibody and syphilis
• Clinically normal findings at the enrolment medical examination, as judged by the investigator(s)
• Homo-EM according to the genotype of CYP2C19
• Less than 30% of time with intragastric pH>4 during the baseline (pre-entry) 24-hr intragastric pH recording
• Helicobacter pylori negative has been known by urea breath test as the volunteer panel data

Exclusion Criteria:

• Significant clinical illness from the 2 weeks preceding the pre-entry visit to the randomisation, as judged by the investigator(s), eg, acute inflammatory disease which requires medical intervention
• Past or present cardiac, renal, hepatic, neurological or gastrointestinal disease, as judged by the investigator(s), eg, sequelae of myocardial infarction, nephritis, hepatitis and cerebral infarction
• Past or present drug addiction or alcohol abuse
• Past or present severe allergic disease, hypersensitivity to food or drugs (except for seasonal hay fever), or allergic symptoms requiring medical intervention
• Moderate to heavy smoking or other sort of nicotine use (greater than 10 cigarettes per day or corresponding nicotine use)
• Clinical significant condition which could modify the absorption of the investigational product, as judged by the investigator(s), eg, effect on the absorption of the investigational product by diarrhoea, or history of excision of parts of the stomach
• Donation of blood in excess of 200 mL during the 1 month, in excess of 400 mL during the 3 months or in excess of 1200 mL during the 12 months before the first dosing of treatment period 1 (including blood component donation)
• Need for concomitant medication in the study
• Use of prescribed medication from the 2 weeks preceding the pre-entry visit to the randomisation, and over the counter (OTC) drugs (including herbs, vitamins and minerals) from one week preceding the pre-entry visit to the randomisation, unless approved by the investigator(s) and sponsor
• Use of grapefruit and grapefruit juice, and health food containing St. John's wort consumption within 2 weeks prior to the first dosing of treatment period 1
• Administration of any investigational product within 4 months preceding the pre-entry visit
• Involvement in the planning and conduct of the study (applies to all AstraZeneca staff and staff at the study site)
• Clinical judgment by the investigator(s) that the subject should not participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: D961H sachet 20 mg; Pellets contains esomeprazole 20 mg (esomeprazole magnesium trihydrate 22.3 mg) and excipient granules filled into single-use aluminium sachets	Drug: D961H sachet 20 mg; Each subject will be randomised evenly to one of "Treatment: A-->B (Sequence 1)" or "Treatment: B-->A (Sequence 2)". Treatment A: D961H sachet 20 mg Treatment B: D961H HPMC capsule 20 mg
OTHER: D961H HPMC capsule 20 mg; Pellets contains esomeprazole 20 mg (esomeprazole magnesium trihydrate 22.3 mg) in HPMC capsule	Drug: D961H HPMC capsule 20 mg; Each subject will be randomised evenly to one of "Treatment: A-->B (Sequence 1)" or "Treatment: B-->A (Sequence 2)". Treatment A: D961H sachet 20 mg Treatment B: D961H HPMC capsule 20 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of whether a D961H sachet 20 mg is bioequivalent to a D961H HPMC capsule 20 mg	To investigate whether a D961H sachet 20 mg is bioequivalent to a D961H HPMC capsule 20 mg after repeated oral doses by the assessment of percentage of time with intragastric pH>4 during 24 hours after dose on Day 5.	27 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description to compare a D961H sachet 20 mg with a D961H HPMC capsule 20 mg by the assessment of percentage of time with intragastric pH>3 during 24 hours and 24-hour median pH	To compare a D961H sachet 20 mg with a D961H HPMC capsule 20 mg after repeated oral doses by the assessment of percentage of time with intragastric pH>3 during 24 hours and 24-hour median pH after dose on Day 5	27 days
Description of the PK properties of a D961H sachet 20 mg with those of D961H HPMC capsule 20 mg.	To compare PK properties of a D961H sachet 20 mg with those of D961H HPMC capsule 20 mg after repeated oral doses by the assessment of AUCτ, Cmax,ss, AUC0-t,ss, MRT, tmax,ss, and t1/2,ss of esomeprazole after dose on Day 5.	27 days
Description of the safety and tolerability of a D961H sachet 20 mg and D961H HPMC capsule 20 mg.	To evaluate the safety and tolerability of a D961H sachet 20 mg and D961H HPMC capsule 20 mg by the assessment of adverse events, clinical laboratory tests, blood pressure (BP), pulse rate and body temperature.	34 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Megumi Inoue, MD, PhD, Hakata Clinic Medical Co. LTA

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: October 14, 2013
• First Submitted That Met QC Criteria: October 14, 2013
• First Posted (ESTIMATE): October 17, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 31, 2013
• Last Update Submitted That Met QC Criteria: December 30, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: tolerability; safety; Bioequivalence; pharmacokinetics; Japanese; pharmacodynamics; D961H
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Diseases; Peptic Ulcer; Duodenal Diseases; Ulcer; Esophagitis, Peptic; Stomach Ulcer; Duodenal Ulcer; Esophagitis
• Other Study ID Numbers: D961TC00004