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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01964131
First received: October 14, 2013
Last updated: December 30, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Gastric Ulcer
Duodenal Ulcer
Anastomotic Ulcer
Reflux Esophagitis
Etc.
Drug: D961H sachet 20 mg
Drug: D961H HPMC capsule 20 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Description of whether a D961H sachet 20 mg is bioequivalent to a D961H HPMC capsule 20 mg [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    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

  • Description of the PK properties of a D961H sachet 20 mg with those of D961H HPMC capsule 20 mg. [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    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.

  • Description of the safety and tolerability of a D961H sachet 20 mg and D961H HPMC capsule 20 mg. [ Time Frame: 34 days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 34
Study Start Date: October 2013
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

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.

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01964131

Locations
Japan
Research Site
Fukuoka-shi, Fukuoka, Japan
Hakata Clinic Medical Co. LTA
Fukuoka, Japan, 812-0025
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Megumi Inoue, MD, PhD Hakata Clinic Medical Co. LTA
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01964131     History of Changes
Other Study ID Numbers: D961TC00004
Study First Received: October 14, 2013
Last Updated: December 30, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by AstraZeneca:
Bioequivalence
pharmacodynamics
pharmacokinetics
safety
tolerability
D961H
Japanese

Additional relevant MeSH terms:
Duodenal Ulcer
Esophagitis
Esophagitis, Peptic
Stomach Ulcer
Ulcer
Digestive System Diseases
Duodenal Diseases
Esophageal Diseases
Gastroenteritis
Gastrointestinal Diseases
Intestinal Diseases
Pathologic Processes
Peptic Ulcer
Stomach Diseases

ClinicalTrials.gov processed this record on October 20, 2014