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

NCT ID: NCT01964131

Last Updated: 2013-12-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2013-12-31

Brief Summary

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.

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.

Conditions

Gastric Ulcer; Duodenal Ulcer; Anastomotic Ulcer; Reflux Esophagitis; Etc.

Keywords

Bioequivalence; pharmacodynamics; pharmacokinetics; safety; tolerability; D961H; Japanese

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

D961H sachet 20 mg

Pellets contains esomeprazole 20 mg (esomeprazole magnesium trihydrate 22.3 mg) and excipient granules filled into single-use aluminium sachets

Group Type: EXPERIMENTAL

D961H sachet 20 mg

Intervention Type: DRUG

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

D961H HPMC capsule 20 mg

Pellets contains esomeprazole 20 mg (esomeprazole magnesium trihydrate 22.3 mg) in HPMC capsule

Group Type: OTHER

D961H HPMC capsule 20 mg

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Megumi Inoue, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hakata Clinic Medical Co. LTA

Locations

Hakata Clinic Medical Co. LTA

Fukuoka, Fukuoka, Japan

Research Site

Fukuoka, Fukuoka, Japan

Countries

Japan

Other Identifiers

D961TC00004

Identifier Type: -

Identifier Source: org_study_id