A Study to Assess the Bioequivalence of Dapagliflozin/Metformin XR Fixed-dose Combination Tablets in Healthy Subjects

Bioequivalence Clinical Trial

Official title:

A Two Part Bioequivalence Study to Compare Two Fixed Dose Combination Tablets of Dapagliflozin/Metformin XR 5/500 mg (Part 1) and 10/1000 mg (Part 2) Manufactured at Two Different Plants in Healthy Subjects Under Fasting and Fed Conditions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02637037
• Other study ID #: D1691C00008
• Status: Completed
• Phase: Phase 1
• First received: December 15, 2015
• Last updated: March 11, 2018
• Start date: December 21, 2015
• Est. completion date: April 7, 2016

Study information

• Verified date: March 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a bioequivalence study to compare 2 fixed-dose combination tablets of dapagliflozin/metformin XR manufactured at 2 different plants in healthy subjects under fasting and fed conditions

Description:

This is a Phase 1, 2-part, open-label, randomized, 4-period, 4-treatment, crossover study in healthy subjects (males and females of non-childbearing potential)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: April 7, 2016
• Est. primary completion date: April 7, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 - 55 years with suitable veins for cannulation or repeated venipuncture

3. Females must have a negative serum pregnancy test at screening and 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 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 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 investigational medicinal product

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

9. 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.

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

11. 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.

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

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

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

15. 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

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

17. Involvement of any AstraZeneca or study site employee or their close relatives

18. 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

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

Related Conditions & MeSH terms

• Bioequivalence
• Fixed Dose Combination Tablets
• Healthy Male and Female Subjects

Intervention

Drug:
• dapagliflozin/metformin XR 5/500 mg test drug (Mount Vernon)
single fixed-combination dose tablets
• dapagliflozin/metformin XR 5/500 mg reference drug (Humacao)
single fixed-dose combination tablets
• dapagliflozin/metformin XR 10/1000 mg test drug (Mount Vernon)
single fixed-dose combination tablets
• dapagliflozin/metformin XR 10/1000 mg reference drug (Humacao)
single fixed-dose combination tablets

Locations

Country	Name	City	State
United States	Research Site	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under Plasma Concentration-time Curve [AUC] Under Fasted or Fed State	To evaluate the Bioequivalence for Dapagliflozin and Metformin following administration Dapagliflozin/Metformin XR 5/500 mg and 10/1000 mg Manufactured at Mt. Vernon plant, US, Compared to Humacao plant, Puerto Rico, in the Fasted or Fed state.	Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
Primary	AUC From Time Zero to Time of Last Quantifiable Concentration [AUC (0-t)] Under Fasted or Fed State.	To evaluate the Bioequivalence for Dapagliflozin and Metformin following administration Dapagliflozin/Metformin XR 5/500 mg and 10/1000 mg Manufactured at Mt. Vernon plant, US, Compared to Humacao plant, Puerto Rico, in the Fasted or Fed state	Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
Primary	Observed Maximum Plasma Concentration [Cmax] Under Fasted or Fed State	To evaluate the Bioequivalence for Dapagliflozin and Metformin following administration Dapagliflozin/Metformin XR 5/500 mg and 10/1000 mg Manufactured at Mt. Vernon plant, US, Compared to Humacao plant, Puerto Rico, in the Fasted or Fed state	Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
Secondary	Time to Reach Maximum Plasma Concentration (t Max)	To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.	Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
Secondary	Half-life Associated With Terminal Slope (?z) of a Semi-logarithmic Concentration-time Curve [t½?z]	To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.	Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
Secondary	Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC [CL/F]	To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.	Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
Secondary	Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration [Vz/F]	To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.	Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period