Type 2 Diabetes MellitusPhase 1NCT03169959
A Study to Evaluate the Food Effect on Drug Availability, Pharmacokinetic (PK) Properties, Safety and Tolerability of Two Different Dose Combination Therapy of Saxagliptin/Dapagliflozin/Metformin Extended-release (XR) Against Individual Component Co-administration.
A Phase 1 study testing 2.5 mg Saxagliptin tablet, 5 mg dapagliflozin / 1000 mg metformin XR tablet and Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 1 site in United States.
Trial summary
A Study to Assess the Fed-state Bioequivalence of a Triple Fixed-Combination Drug Product (FCDP) of 2.5 mg Saxagliptin / 5 mg Dapagliflozin / 1000 mg Metformin XR and 5 mg Saxagliptin /10 mg Dapagliflozin /1000 mg Metformin XR Relative to Individual Components (Onglyza and XIGDUO XR) Co-administration. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- 2.5 mg Saxagliptin tablet, 5 mg dapagliflozin / 1000 mg metformin XR tablet and Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2017to 3 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- Female subject 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 investigational medicinal product (IMP) administration and either: a) Be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria: - Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
- b). Or, if of childbearing potential: - Must not be nursing (breastfeeding). -And, if heterosexually active, agree to consistently use an acceptable 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.
- 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.
- 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.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the principal investigator (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.
- Current or recent (within 3 months of first IMP dosing) gastrointestinal (GI) disease that may impact drug absorption and affect the PK of the study drugs. Additionally, any GI surgery (e.g., partial gastrectomy, pyloroplasty) including cholecystectomy that may impact drug absorption.
- Any major surgery, as determined by the investigator, within 4 weeks of first IMP dosing.
- 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.
- Blood transfusion within 4 weeks of first IMP dosing.
- Inability to tolerate oral medication.
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- Inability to tolerate venipuncture or inadequate venous access as determined by the investigator.
- 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.
- Subjects who drink more than 3 cups of coffee or other caffeine-containing products a day, or 5 cups of tea a day.
- 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.
- History of diabetes mellitus, heart failure, chronic or recurrent urinary tract infection (defined as 3 occurrences per year) and 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.
- 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.
- 19. Positive screen for drugs of abuse or cotinine at Screening or on each admission to the clinical unit or positive screen for alcohol on each admission to the clinical unit.
- 20. Use of saxagliptin, dapagliflozin and/or metformin within 3 months prior to the first administration of IMP.
- 21. Use of any prescription drugs or over the counter acid controllers within 4 weeks prior to the first administration of IMP except medication cleared by the medical monitor.
- 22. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- 23. 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.
- 24. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
- 25. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, 3-Period, 3-Treatment, Single-dose, Open-label, Single-center, Crossover Study to Assess the Fed-state Bioequivalence of a Triple Fixed-Combination Drug Product of 2.5 mg Saxagliptin / 5 mg Dapagliflozin / 1000 mg Metformin XR and 5 mg Saxagliptin / 10 mg Dapagliflozin / 1000 mg Metformin XR Relative to Individual Components (Onglyza® and XIGDUO® XR) Co-administered to Healthy Subjects
A Study to Assess the Fed-state Bioequivalence of a Triple Fixed-Combination Drug Product (FCDP) of 2.5 mg Saxagliptin / 5 mg Dapagliflozin / 1000 mg Metformin XR and 5 mg Saxagliptin /10 mg Dapagliflozin /1000 mg Metformin XR Relative to Individual Components (Onglyza and XIGDUO XR) Co-administration. A randomized, open-label, cross over design has been chosen to minimize the effects of between-subject variability and any period effects on the overall results.
Read the detailed description
This study will be randomized, 3-period, 3-treatment, single-dose, open-label, single-center, crossover to assess the fed-state bioequivalence of a two triple Fixed-combination Drug Product (FCDP) of saxagliptin/dapagliflozin/metformin extended-release (XR) relative to individual components co-administered in approximately 84 healthy adult subjects. Eligible subjects will be healthy male and female aged 18 to 55 years, with a body weight of 50 to 100 kg and body mass index (BMI) of 18 to 32 kg/m2. Of the 84 randomized subjects (2 cohorts of 42 subjects each [3 treatments in each cohort]), at least 72 subjects (36 in each cohort) should be evaluable. Each randomized subject will receive 3 single-dose treatments and each treatment will be administered within 1 of the 3 successive treatment periods. Within each cohort subjects will be randomized to 1 to 6 treatment sequences prescribing the ordered sequence of 3 administered treatments with 7 subjects in each treatment sequence. The investigational medicinal product (IMPs) will be administered orally at single-dose to subjects within 5 minutes after standard meal (light-fat, low-calorie) in the morning (fed condition) or following a 10 hour fast (fasted condition). In both cohorts, test product will be compared with treatments of fed and fasted conditions Subjects in Cohort 1 will be randomized to one of the treatment sequences (ABC), (ACB), (BAC), (BCA), (CAB) or (CBA).
Treatment A (Reference Product under fed conditions) - Single-dose of 2.5 mg saxagliptin (ONGLYZA) and 5 mg dapagliflozin / 1000 mg metformin XR (XIGDUO XR) tablets.
Treatment B (Test Product under fed conditions) - Single-dose of triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR.
Treatment C (Test Product fasted conditions) - Single-dose of triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR.
Subjects in Cohort 2 will be randomized to one of the treatment sequences (DEF), (DFE), (EDF), (EFD), (FDE) or (FED).
Treatment D (Reference product under fed conditions) - Single-dose of 5 mg saxagliptin (ONGLYZA) and 10 mg dapagliflozin / 1000 mg metformin XR (XIGDUO XR) tablet.
Treatment E (Test Product under fed conditions) - Single-dose of triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR.
Treatment F (Test Product under fasted conditions) - Single-dose of triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR.
The study will comprise:
- A screening period of maximum 28 days;
- Three resident treatment periods - Day before dosing with the IMP (Day -1) until at least 72 hours after dosing; and will be discharged on the morning of Day 4; and
- A follow-up visit within 5 to 7 days after the last dose of IMP. Treatment periods will be separated by a minimum washout period of 7 to 14 days between each IMP dose. The duration of the study will be approximately 7 to 9 weeks.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- 2.5 mg Saxagliptin tablet, 5 mg dapagliflozin / 1000 mg metformin XR tablet, Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR, 5 mg saxagliptin, 10 mg dapagliflozin / 1000 mg metformin XR tablet
- Keywords
- Anti-diabetic, Anti-hyperglycemic agents, Bioequivalence, Fixed-Combination Drug Product (FCDP) of saxagliptin / dapagliflozin / metformin extended-release (XR)., Fed-state bioequivalence (BE), XIGDUO® XR, ONGLYZA®
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2.5 mg Saxagliptin tabletDrug
Also called 2.5 mg ONGLYZA
A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with Type 2 diabetes mellitus (T2DM).
5 mg dapagliflozin / 1000 mg metformin XR tabletDrug
Also called 5 / 1000 mg XIGDUO XR
Dapagliflozin - An inhibitor of sodium-glucose co-transporter 2 (SGLT-2), reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRDrug
Saxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM.
Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
5 mg saxagliptinDrug
Also called 5 mg ONGLYZA
A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM.
10 mg dapagliflozin / 1000 mg metformin XR tabletDrug
Also called 10/1000 mg XIGDUO XR
Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRDrug
Saxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM.
Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Sequence 1 (ABC) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food.
B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food.
C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 2.5 mg Saxagliptin tablet; Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 1: Sequence 2 (ACB) | Experimental | Subjects were randomized to treatment sequence 1 ACB:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food.
B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food.
C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 2.5 mg Saxagliptin tablet; Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 1: Sequence 3 (BAC) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food.
B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food.
C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 2.5 mg Saxagliptin tablet; Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 1: Sequence 4 (BCA) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food.
B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food.
C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 2.5 mg Saxagliptin tablet; Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 1: Sequence 5 (CAB) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food.
B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food.
C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 2.5 mg Saxagliptin tablet; Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 1: Sequence 6 (CBA) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food.
B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food.
C = Test product - Triple FCDP tablet consisting of 2.5mg saxagliptin / 5mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 2.5 mg Saxagliptin tablet; Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 2: Sequence 1 (DEF) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food.
E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food.
F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 5 mg saxagliptin; Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 2: Sequence 2 (DFE) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food.
E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food.
F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 5 mg saxagliptin; Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 2: Sequence 3 (EDF) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
D= 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food.
E = Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food.
F = Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 5 mg saxagliptin; Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 2: Sequence 4 (EFD) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food.
E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food.
F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 5 mg saxagliptin; Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR |
| Cohort 2: Sequence 5 (FDE) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food.
E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food.
F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 5 mg saxagliptin; Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR |
| COhort 2: Sequence 6 (FED) | Experimental | Subjects were randomized to treatment sequence 1 ABC:
On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period.
D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food.
E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food.
F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. Receives: Drug: 5 mg saxagliptin; Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet; Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration-time curve from time zero to infinity (AUC)
To assess pharmacokinetics (PK) in terms of AUC in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
To assess PK in terms of AUC0-t in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)
Maximum observed plasma concentration (Cmax)
To assess PK in terms of Cmax in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)
Secondary outcomes (15)
Time to reach maximum observed plasma concentration (tmax)
To assess PK in terms of tmax in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2)
To assess PK in terms of t1/2 in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (parent drug only) (MRT)
To assess PK in terms of MRT in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Terminal elimination rate constant (λz)
To assess PK in terms of λz in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To assess PK in terms of CL/F in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Apparent volume of distribution (V/F)
To assess PK in terms of V/F in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Ratio of metabolite AUC to parent AUC (MRAUC)
To assess PK in terms of MRAUC in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Measured: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Number of subjects with Adverse Events (AEs)
To assess AEs as a criteria of safety and tolerability variables.
Measured: A Day -1, spontaneous plus pre-dose, 1, 2, 3, 24, and 48 hours post-dose
Systolic and diastolic blood pressure [BP]
To assess the systolic and diastolic blood pressure as a criteria of safety and tolerability variables
Measured: At screening (Day -28), Day -1, pre-dose, 71 hours post-dose and 5 to 7 days post-final dose follow-up
Pulse rate
To assess the pulse rate as a criteria of safety and tolerability variables
Measured: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Twelve-lead electrocardiograms (ECGs)
To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
Measured: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Physical examination
To assess a complete physical examinations (general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal and neurological systems) and a brief physical examinations (general appearance, skin, abdomen, cardiovascular system and respiratory) as a criteria of safety and tolerability variables.
A complete physical examination will be performed at the screening visit.
Measured: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Laboratory assessments of Hematology
To assess the count of white blood cell (WBC), red blood cell (RBC) and platelets; absolute count of neutrophils, lymphocytes, monocytes, eosinophils, basophils and reticulocytes; levels of Hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) in blood as a criteria of safety and tolerability variables.
Measured: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Laboratory assessments of Clinical chemistry
To assess the levels of electrolytes (sodium, potassium, magnesium, chloride, calcium, phosphate), urea, creatinine, albumin, glucose (fasting), C-reactive protein (CRP), thyroxine (T4), thyroid-stimulating hormone (TSH), liver enzymes (alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT)), bilirubin (total and unconjugated) and follicle-stimualting hormone (FSH) in serum as a criteria of safety and tolerability variables.
Measured: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Laboratory assessments of urinalysis
To assess the presence of glucose, protein, blood and microscopy (RBC, WBC, casts (cellualr, granular, hyaline) in urine as a criteria of safety and tolerability variables.
Measured: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start29 May 2017
- Primary completion3 Aug 2017
- Study completion3 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03169959
- Sponsor's protocol ID
- D168AC00001
- Status last verified
- Aug 2017
- First submitted
- 23 May 2017
- Last updated
- 14 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Tang W, Engman H, Zhu Y, Dayton B, Boulton DW. Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects. Clin Ther. 2019 Aug;41(8):1545-1563. doi: 10.1016/j.clinthera.2019.05.015. Epub 2019 Jun 29.
PubMed 31266654
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, 3-Period, 3-Treatment, Single-dose, Open-label, Single-center, Crossover Study to Assess the Fed-state Bioequivalence of a Triple Fixed-Combination Drug Product of 2.5 mg Saxagliptin / 5 mg Dapagliflozin / 1000 mg Metformin XR and 5 mg Saxagliptin / 10 mg Dapagliflozin / 1000 mg Metformin XR Relative to Individual Components (Onglyza® and XIGDUO® XR) Co-administered to Healthy Subjects
- ClinicalTrials.gov ID
- NCT03169959
- Acronym / sponsor ID
- D168AC00001
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Anti-diabetic, Anti-hyperglycemic agents, Bioequivalence, Fixed-Combination Drug Product (FCDP) of saxagliptin / dapagliflozin / metformin extended-release (XR)., Fed-state bioequivalence (BE), XIGDUO® XR, ONGLYZA®
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 29 May 2017 (actual)
- Primary completion
- 3 Aug 2017 (actual)
- Study completion
- 3 Aug 2017 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Study to Assess the Fed-state Bioequivalence of a Triple Fixed-Combination Drug Product (FCDP) of 2.5 mg Saxagliptin / 5 mg Dapagliflozin / 1000 mg Metformin XR and 5 mg Saxagliptin /10 mg Dapagliflozin /1000 mg Metformin XR Relative to Individual Components (Onglyza and XIGDUO XR) Co-administration. A randomized, open-label, cross over design has been chosen to minimize the effects of between-subject variability and any period effects on the overall results.
Detailed description
This study will be randomized, 3-period, 3-treatment, single-dose, open-label, single-center, crossover to assess the fed-state bioequivalence of a two triple Fixed-combination Drug Product (FCDP) of saxagliptin/dapagliflozin/metformin extended-release (XR) relative to individual components co-administered in approximately 84 healthy adult subjects. Eligible subjects will be healthy male and female aged 18 to 55 years, with a body weight of 50 to 100 kg and body mass index (BMI) of 18 to 32 kg/m2. Of the 84 randomized subjects (2 cohorts of 42 subjects each [3 treatments in each cohort]), at least 72 subjects (36 in each cohort) should be evaluable. Each randomized subject will receive 3 single-dose treatments and each treatment will be administered within 1 of the 3 successive treatment periods. Within each cohort subjects will be randomized to 1 to 6 treatment sequences prescribing the ordered sequence of 3 administered treatments with 7 subjects in each treatment sequence. The investigational medicinal product (IMPs) will be administered orally at single-dose to subjects within 5 minutes after standard meal (light-fat, low-calorie) in the morning (fed condition) or following a 10 hour fast (fasted condition). In both cohorts, test product will be compared with treatments of fed and fasted conditions Subjects in Cohort 1 will be randomized to one of the treatment sequences (ABC), (ACB), (BAC), (BCA), (CAB) or (CBA).
Treatment A (Reference Product under fed conditions) - Single-dose of 2.5 mg saxagliptin (ONGLYZA) and 5 mg dapagliflozin / 1000 mg metformin XR (XIGDUO XR) tablets.
Treatment B (Test Product under fed conditions) - Single-dose of triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR.
Treatment C (Test Product fasted conditions) - Single-dose of triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR.
Subjects in Cohort 2 will be randomized to one of the treatment sequences (DEF), (DFE), (EDF), (EFD), (FDE) or (FED).
Treatment D (Reference product under fed conditions) - Single-dose of 5 mg saxagliptin (ONGLYZA) and 10 mg dapagliflozin / 1000 mg metformin XR (XIGDUO XR) tablet.
Treatment E (Test Product under fed conditions) - Single-dose of triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR.
Treatment F (Test Product under fasted conditions) - Single-dose of triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR.
The study will comprise:
- A screening period of maximum 28 days;
- Three resident treatment periods - Day before dosing with the IMP (Day -1) until at least 72 hours after dosing; and will be discharged on the morning of Day 4; and
- A follow-up visit within 5 to 7 days after the last dose of IMP. Treatment periods will be separated by a minimum washout period of 7 to 14 days between each IMP dose. The duration of the study will be approximately 7 to 9 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Sequence 1 (ABC) | Experimental | Drug: 2.5 mg Saxagliptin tablet, Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 1: Sequence 2 (ACB) | Experimental | Drug: 2.5 mg Saxagliptin tablet, Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ACB: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 1: Sequence 3 (BAC) | Experimental | Drug: 2.5 mg Saxagliptin tablet, Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 1: Sequence 4 (BCA) | Experimental | Drug: 2.5 mg Saxagliptin tablet, Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 1: Sequence 5 (CAB) | Experimental | Drug: 2.5 mg Saxagliptin tablet, Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 1: Sequence 6 (CBA) | Experimental | Drug: 2.5 mg Saxagliptin tablet, Drug: 5 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5mg saxagliptin / 5mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 2: Sequence 1 (DEF) | Experimental | Drug: 5 mg saxagliptin, Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 2: Sequence 2 (DFE) | Experimental | Drug: 5 mg saxagliptin, Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 2: Sequence 3 (EDF) | Experimental | Drug: 5 mg saxagliptin, Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 2: Sequence 4 (EFD) | Experimental | Drug: 5 mg saxagliptin, Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. |
| Cohort 2: Sequence 5 (FDE) | Experimental | Drug: 5 mg saxagliptin, Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. |
| COhort 2: Sequence 6 (FED) | Experimental | Drug: 5 mg saxagliptin, Drug: 10 mg dapagliflozin / 1000 mg metformin XR tablet, Drug: Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- Female subject 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 investigational medicinal product (IMP) administration and either: a) Be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria: - Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
- b). Or, if of childbearing potential: - Must not be nursing (breastfeeding). -And, if heterosexually active, agree to consistently use an acceptable 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.
- 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.
Key exclusion criteria (23 listed)
- History of any clinically significant disease or disorder which, in the opinion of the principal investigator (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.
- Current or recent (within 3 months of first IMP dosing) gastrointestinal (GI) disease that may impact drug absorption and affect the PK of the study drugs. Additionally, any GI surgery (e.g., partial gastrectomy, pyloroplasty) including cholecystectomy that may impact drug absorption.
- Any major surgery, as determined by the investigator, within 4 weeks of first IMP dosing.
- 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.
- Blood transfusion within 4 weeks of first IMP dosing.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2.5 mg Saxagliptin tabletAlso: 2.5 mg ONGLYZAA competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with Type 2 diabetes mellitus (T2DM). | Drug | Cohort 1: Sequence 1 (ABC), Cohort 1: Sequence 2 (ACB), Cohort 1: Sequence 3 (BAC), Cohort 1: Sequence 4 (BCA), Cohort 1: Sequence 5 (CAB), Cohort 1: Sequence 6 (CBA) |
| 5 mg dapagliflozin / 1000 mg metformin XR tabletAlso: 5 / 1000 mg XIGDUO XRDapagliflozin - An inhibitor of sodium-glucose co-transporter 2 (SGLT-2), reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization. | Drug | Cohort 1: Sequence 1 (ABC), Cohort 1: Sequence 2 (ACB), Cohort 1: Sequence 3 (BAC), Cohort 1: Sequence 4 (BCA), Cohort 1: Sequence 5 (CAB), Cohort 1: Sequence 6 (CBA) |
| Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRSaxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM. Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization. | Drug | Cohort 1: Sequence 1 (ABC), Cohort 1: Sequence 2 (ACB), Cohort 1: Sequence 3 (BAC), Cohort 1: Sequence 4 (BCA), Cohort 1: Sequence 5 (CAB), Cohort 1: Sequence 6 (CBA) |
| 5 mg saxagliptinAlso: 5 mg ONGLYZAA competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM. | Drug | COhort 2: Sequence 6 (FED), Cohort 2: Sequence 1 (DEF), Cohort 2: Sequence 2 (DFE), Cohort 2: Sequence 3 (EDF), Cohort 2: Sequence 4 (EFD), Cohort 2: Sequence 5 (FDE) |
| 10 mg dapagliflozin / 1000 mg metformin XR tabletAlso: 10/1000 mg XIGDUO XRDapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization. | Drug | COhort 2: Sequence 6 (FED), Cohort 2: Sequence 1 (DEF), Cohort 2: Sequence 2 (DFE), Cohort 2: Sequence 3 (EDF), Cohort 2: Sequence 4 (EFD), Cohort 2: Sequence 5 (FDE) |
| Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRSaxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM. Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization. | Drug | COhort 2: Sequence 6 (FED), Cohort 2: Sequence 1 (DEF), Cohort 2: Sequence 2 (DFE), Cohort 2: Sequence 3 (EDF), Cohort 2: Sequence 4 (EFD), Cohort 2: Sequence 5 (FDE) |
Primary outcome
Area under plasma concentration-time curve from time zero to infinity (AUC)
Time frame: Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)
To assess pharmacokinetics (PK) in terms of AUC in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
Time frame: Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)
To assess PK in terms of AUC0-t in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
Maximum observed plasma concentration (Cmax)
Time frame: Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)
To assess PK in terms of Cmax in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.
15 secondary outcomes
Time to reach maximum observed plasma concentration (tmax)
Time frame: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2)
Time frame: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (parent drug only) (MRT)
Time frame: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Terminal elimination rate constant (λz)
Time frame: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Time frame: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Apparent volume of distribution (V/F)
Time frame: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Ratio of metabolite AUC to parent AUC (MRAUC)
Time frame: At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours
Number of subjects with Adverse Events (AEs)
Time frame: A Day -1, spontaneous plus pre-dose, 1, 2, 3, 24, and 48 hours post-dose
Systolic and diastolic blood pressure [BP]
Time frame: At screening (Day -28), Day -1, pre-dose, 71 hours post-dose and 5 to 7 days post-final dose follow-up
Pulse rate
Time frame: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Twelve-lead electrocardiograms (ECGs)
Time frame: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Physical examination
Time frame: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Laboratory assessments of Hematology
Time frame: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Laboratory assessments of Clinical chemistry
Time frame: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Laboratory assessments of urinalysis
Time frame: From Screening (Day -28 to Day -1) to Follow-up (5-7days post final dose)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2017.
- Derived from this study: PubMed 31266654Tang W, Engman H, Zhu Y, Dayton B, Boulton DW. Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects. Clin Ther. 2019 Aug;41(8):1545-1563. doi: 10.1016/j.clinthera.2019.05.015. Epub 2019 Jun 29.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 2.5 mg Saxagliptin tablet, 5 mg dapagliflozin / 1000 mg metformin XR tablet and Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under plasma concentration-time curve from time zero to infinity (AUC) (time frame: Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03169959, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2017.