Bioequivalence Study of Combination Tablets of Saxagliptin / Dapagliflozin / Metformin XR (Extended-release) and Dapagliflozin / Metformin XR Relative to Individual Components in Healthy Subjects

• Status: Completed
• Trial end date: 2017-11-28
• Target enrollment: 0
• Participant gender: All

Summary

In this integrated, Phase I study, the safety, tolerability, food effect, and pharmacokinetic (PK) properties of Fixed-Dose Combination Tablets of Saxagliptin / Dapagliflozin / Metformin XR and Dapagliflozin / Metformin XR Relative to Individual Components in Healthy Subjects will be investigated.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AstraZeneca
• Treatments: Dapagliflozin; Metformin; Saxagliptin

Criteria

Inclusion Criteria:

• For inclusion in the study subjects should fulfill the following criteria:

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

2. Healthy male and/or female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.

3. Female subject must either:

3.1. Be of non-childbearing potential:

• Must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) at Screening and negative urine pregnancy test within 24 hours prior to first IMP administration.

• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. 3.2. Or, if of childbearing potential:

• Must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) at Screening and within 24 hours prior to first IMP administration.

• Must not be nursing (breastfeeding).

• If heterosexually active, agree to consistently use a highly effective method of contraception to avoid pregnancy, from at least 4 weeks prior to dosing and throughout the study and for up to 90 days after the last dose of IMP. 4. Sexually active fertile male subjects must use effective birth control for the entire study and 90 days after the last dose of IMP if their partners are women of childbearing potential. 5. Have a body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria:

• Subjects will not enter the study if any of the following exclusion criteria are fulfilled:

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

2. Current or recent (within 3 months of first IMP dosing) gastrointestinal disease that may impact drug absorption and affect the PK of the study drugs. Additionally, any gastrointestinal surgery (e.g., partial gastrectomy, pyloroplasty) including cholecystectomy that may impact drug absorption.

3. Any major surgery, as determined by the investigator, within 4 weeks of first IMP dosing.

4. Donation of > 400 mL of blood within 8 weeks or donation of plasma (except at the Screening Visit) within 4 weeks of first IMP dosing.

5. Blood transfusion within 4 weeks of first IMP dosing.

6. Inability to tolerate oral medication.

7. Inability to tolerate venipuncture or inadequate venous access as determined by the investigator.

8. Recent (within 6 months of first IMP dosing) drug or alcohol abuse as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Diagnostic Criteria for Drug and Alcohol Abuse.

9. Subjects who drink more than 3 cups of coffee or other caffeinecontaining products a day, or 5 cups of tea a day.

10. Use of tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to first check-in (Day -1, Treatment Period 1), or a positive nicotine test (i.e., cotinine) at Screening and/or check-in.

11. History of diabetes mellitus.

12. History of heart failure.

13. History of chronic or recurrent urinary tract infection (defined as 3 occurrences per year)

14. Recent vulvovaginal mycotic infection (within 2 months prior to first IMP dosing).

15. Any other sound medical, psychiatric and/or social reason as determined by the investigator.

16. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of Screening.

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

18. 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 or one month after the last visit whichever is the longest. Note: subjects consented and screened, but not randomized in this study or a previous Phase1 study, are not excluded.

19. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to saxagliptin, dapagliflozin and metformin.

20. Positive screen for drugs of abuse or cotinine at Screening or on first admission to the study center or positive screen for alcohol on first admission to the study center

21. Use of saxagliptin, dapagliflozin and/or metformin within 3 months prior to the first administration of IMP.

22. Use of any prescription drugs or OTC acid controllers within 4 weeks prior to the first administration of IMP except medication cleared by the medical monitor.

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

24. Use of any prescribed or non-prescribed medication including analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) 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 not allowed.

25. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.

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