The Purpose of the Study is to Compare Two Fixed Dose Combination Tablets of Dapagliflozin/Metformin XR in Healthy Subjects Under Fasting and Fed Conditions

NCT ID: NCT03216278

Last Updated: 2018-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 284 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-26
• Study Completion Date: 2018-05-22

Brief Summary

This is a bioequivalence study of two doses of the dapagliflozin/metformin XR tablet manufactured at two different plants.

Detailed Description

This is a two part, open-label, randomized, 4-period, 4-treatment (per study part) crossover study in healthy subjects (males and females of non-childbearing potential), performed at a single study center, conducted to establish the bioequivalence of 2 strengths of dapagliflozin/metformin XR tablets manufactured at two different plants.

Conditions

Healthy Subjects in Fasted and Fed State

Study Design

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

Study Groups

Treatment A

Dapagliflozin/metformin XR 5/500 Mount Vernon Test Product Fed

Group Type: EXPERIMENTAL

Dapagliflozin/metformin XR 5/500mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Treatment B

Dapagliflozin/metformin XR 5/500 Humacao Reference Product Fed

Group Type: ACTIVE_COMPARATOR

Dapagliflozin/metformin XR 5/500 mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Treatment C

Dapagliflozin/metformin XR 5/500 Mount Vernon Test Product Fasted

Group Type: EXPERIMENTAL

Dapagliflozin/metformin XR 5/500mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Treatment D

Dapagliflozin/metformin XR 5/500 Humacao Reference Product Fasted

Group Type: ACTIVE_COMPARATOR

Dapagliflozin/metformin XR 5/500mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Treatment E

Dapagliflozin/metformin XR 10/1000 Mount Vernon Test Product Fed

Group Type: EXPERIMENTAL

Dapagliflozin/metformin XR 10/1000mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Treatment F

Dapagliflozin/metformin XR 10/1000 Humacao Reference Product Fed

Group Type: ACTIVE_COMPARATOR

Dapagliflozin/metformin XR 10/1000mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Treatment G

Dapagliflozin/metformin XR 10/1000 Mount Vernon Test Product Fasted

Group Type: EXPERIMENTAL

Dapagliflozin/metformin XR 10/1000mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Treatment H

Dapagliflozin/metformin XR 10/1000 Humacao Reference Product Fasted

Group Type: ACTIVE_COMPARATOR

Dapagliflozin/metformin XR 10/1000mg

Intervention Type: DRUG

Tablets for oral administration, once daily, once per treatment period

Interventions

Dapagliflozin/metformin XR 5/500mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Dapagliflozin/metformin XR 5/500 mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Dapagliflozin/metformin XR 5/500mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Dapagliflozin/metformin XR 5/500mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Dapagliflozin/metformin XR 10/1000mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Dapagliflozin/metformin XR 10/1000mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Dapagliflozin/metformin XR 10/1000mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Dapagliflozin/metformin XR 10/1000mg

Tablets for oral administration, once daily, once per treatment period

Intervention Type: DRUG

Other Intervention Names

Mt Vernon plant; Humacao plant; Dapagliflozin/metformin XR 5/500mg Mount Vernon plant; Humacao plant; Mount Vernon plant; Humacao plant; Dapagliflozin/metformin XR 10/1000mg Mount Vernon plant; Dapagliflozin/metformin XR 10/1000mg Humacao plant

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated, written informed consent prior to any study-specific procedures

2. Healthy male and female subjects aged 18 - 50 years with suitable veins for cannulation or repeated venipuncture

3. Females must have a negative serum pregnancy test at screening and negative urine pregnancy test on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:

• Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post menopausal range
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation

4. Have a body mass index (BMI) between 18.50 and 24.90 kg/m2 inclusive [15% variance on the upper limit is permitted (i.e., up to 28.63 kg/m2)] and weigh between 50 and 100 kg inclusive at screening

Exclusion Criteria

1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study

2. History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs

3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP

4. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the investigator

5. Any clinically significant abnormal findings in vital signs, as judged by the investigator

6. Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) as judged by the investigator

7. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody

8. Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN

9. Total bilirubin >2.0 mg/dL (34.2 µmol/L)

10. Known or suspected history of drug abuse, as judged by the investigator

11. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose.

Note: Subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded.

12. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening

13. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to dapagliflozin/metformin XR.

14. Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening.

15. Positive screen for drugs of abuse or alcohol at screening or on each admission to the study center

16. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP

17. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, vitamins and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life Note: Hormonal replacement therapy is allowed for females.

18. Known or suspected history of alcohol abuse or excessive intake of alcohol, as judged by the investigator

19. Inclusion of any AstraZeneca or study site employee or their close relatives

20. Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements

21. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Aparecida de Goiânia, , Brazil

Countries

Brazil

Other Identifiers

D1691C00016

Identifier Type: -

Identifier Source: org_study_id