Type 2 Diabetes Mellitus
Conditions
Brief summary
To demonstrate the bioequivalence of saxagliptin and metformin in a saxagliptin, 5-mg/metformin extended-release (XR), 500-mg, fixed-dose combination (FDC) tablet with saxagliptin, 5-mg and metformin, 500-mg XR tablets administered together in both the fasted and fed states. In addition, to demonstrate the bioequivalence of saxagliptin and metformin in a saxagliptin, 5-mg/metformin XR, 1000-mg, FDC tablet with saxagliptin, 5-mg and metformin, 1000-mg XR tablets administered together in both the fasted and fed states.
Interventions
DRUGSaxagliptin/metformin fixed-dose combination (FDC)
Tablet, oral, 5 mg/500 mg FDC, once on Day 1 only, 1 day
DRUGSaxagliptin
Tablet, oral, 5 mg, once on Day 1 only, 1 day
DRUGMetformin extended-release (XR)
Tablet, oral, 500 mg, once on Day 1 only, 1 day
DRUGSaxagliptin/Metformin FDC
Tablet, Oral, 5 mg/1000 mg FDC, once on Day 1 only, 1 day
DRUGMetformin
Tablet, oral, 1000 mg, once on Day 1 only, 1 day
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy men and women * women of childbearing potential who are using acceptable method of contraception * Women who are not pregnant or nursing * Body Mass Index (BMI) of 18 to 29.9 kg/m\^2, inclusive. BMI=weight(kg)/height(m)\^2. Key
Exclusion criteria
* Any significant acute or chronic medical illness. * History of gastrointestinal (GI) disease * Major surgery within 4 weeks of study drug administration * Any GI surgery that could impact study drug absorption * Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within the 6 months of study drug administration. * Blood transfusion within 3 months of study drug administration for women and within 2 months for men * Inability to be venipunctured and/or tolerate venous access * Current smoker or recent (within 1 month) history of regular tobacco use * Recent (within 6 months of study drug administration) drug or alcohol abuse * Participation in a bioequivalence study within the last 6 months of study drug administration * Estimated creatinine clearance of \<80 mL/min using Cockcroft-Gault formula * History of allergy to drug class or related compounds * History of allergy to metformin or other similar acting agents * History of any significant drug allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Days 1, 2, and 3 of Periods 1 and 2 | — |
| AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Days 1, 2, and 3 of Periods 1 and 2 | AUC=Area under the concentration-time curve |
| AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Days 1, 2, and 3 of Periods 1 and 2 | AUC=Area Under the Concentration-time Curve |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | Continuously, from screening through Day 1 to within 30 days of drug discontinuation on Day 1 | SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Treatments A/B, B/A Period 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg fixed-dose combination (FDC) in the fasted state (Treatment A), followed by a washout period of at least 7 days. Then, participants received single oral doses of saxagliptin, 5-mg, and metformin extended-release (XR), 500-mg, tablets together in the fasted state (Treatment B). Followed by a washout period of at least 4 days.
Period 2: Participants received single oral doses of saxagliptin, 5-mg and metformin XR, 500-mg tablets together in the fasted state (Treatment B), followed by a washout period of at least 7 days. Then, participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg FDC, in the fasted state (Treatment A). | 28 |
| Arm 2: Treatments C/D, D/C Period 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg fixed-dose combination (FDC), in the fed state (Treatment C), followed by a washout period of at least 7 days. Then, participants received a single oral dose of saxagliptin, 5-mg, and metformin extended-release (XR), 500-mg tablets together in the fed state (Treatment D). Followed by a washout period of at least 4 days.
Period 2: Participants received a single oral dose of saxagliptin, 5-mg and metforminXR, 500-mg tablets together in the fed state (Treatment D), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg FDC, in the fed state (Treatment C). | 28 |
| Arm 3:Treatments E/ F, F/E Period 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg fixed-dose combination (FDC), in the fasted state (Treatment E), followed by a washout period of at least 7 days. Participants received single oral doses of saxagliptin, 5-mg and metformin extended-release (XR), 1000-mg tablets together in the fasted state (Treatment F). Followed by a washout period of at least 4 days.
Period 2: Participants received single oral doses of saxagliptin, 5- mg and metformin XR, 1000-mg tablets together in the fasted state (Treatment F), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg FDC, in the fasted state (Treatment E). | 28 |
| Arm 4: Treatments G/ H, H/G Period 1: Participants received a single oral dose of saxagliptin , 5 mg/metformin, 1000 mg fixed-dose combination (FDC), in the fed state (Treatment G), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5-mg and metformin extended-release (XR), 1000-mg tablets together in the fed state (Treatment H). Followed by a washout period of at least 4 days.
Period 2: Participants received a single oral dose of saxagliptin, 5-mg and metformin XR, 1000-mg tablets together in the fed state (Treatment H), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg FDC, in the fed state (Treatment G). | 28 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 | 2 | 3 |
| Period 1 | No longer met study criteria | 0 | 1 | 0 | 0 |
| Period 1 | Personal reasons | 0 | 0 | 1 | 0 |
| Period 1 | Positive test result for drugs of abuse | 1 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 1 | 0 |
| Period 2 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1: Treatments A/B, B/A | Arm 2: Treatments C/D, D/C | Arm 3:Treatments E/ F, F/E | Arm 4: Treatments G/ H, H/G | Total |
|---|---|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=55 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 18 and 55 years | 28 Participants | 28 Participants | 28 Participants | 28 Participants | 112 Participants |
| Sex/Gender, Customized Both genders | 28 Participants | 28 Participants | 28 Participants | 28 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 28 | 13 / 26 | 10 / 27 | 6 / 26 | 8 / 25 | 4 / 27 | 8 / 28 | 14 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
Primary
AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets
AUC=Area Under the Concentration-time Curve
Time frame: Days 1, 2, and 3 of Periods 1 and 2
Population: Participants who received study medication and were evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (individual tablets) | 5877 ng*h/mL | Standard Deviation 1858 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (FDC) | 5443 ng*h/mL | Standard Deviation 1905 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (individual tablets) | 107425 ng*h/mL | Standard Deviation 26828 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (FDC) | 105248 ng*h/mL | Standard Deviation 31314 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (individual tablets) | 337345 ng*h/mL | Standard Deviation 67941 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (FDC) | 326501 ng*h/mL | Standard Deviation 68475 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (FDC) | 298037 ng*h/mL | Standard Deviation 45636 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (FDC) | 110705 ng*h/mL | Standard Deviation 24091 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (individual tablets) | 5127 ng*h/mL | Standard Deviation 816 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (individual tablets) | 111677 ng*h/mL | Standard Deviation 22315 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (FDC) | 4754 ng*h/mL | Standard Deviation 1037 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (individual tablets) | 310983 ng*h/mL | Standard Deviation 53447 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (FDC) | 8618 ng*h/mL | Standard Deviation 2726 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (individual tablets) | 104293 ng*h/mL | Standard Deviation 22149 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (FDC) | 100620 ng*h/mL | Standard Deviation 20264 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (FDC) | 329085 ng*h/mL | Standard Deviation 56298 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (individual tablets) | 330247 ng*h/mL | Standard Deviation 59863 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (individual tablets) | 8338 ng*h/mL | Standard Deviation 2414 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (individual tablets) | 332495 ng*h/mL | Standard Deviation 62192 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC (0-inf) (FDC) | 332869 ng*h/mL | Standard Deviation 59469 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (FDC) | 9054 ng*h/mL | Standard Deviation 2684 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (FDC) | 128602 ng*h/mL | Standard Deviation 28729 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC (0-inf) (individual tablets) | 9731 ng*h/mL | Standard Deviation 3277 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC (0-inf) (individual tablets) | 125820 ng*h/mL | Standard Deviation 24856 |
90% CI: [82.697, 101.226]ANCOVA
90% CI: [93.955, 101.132]ANCOVA
90% CI: [93.393, 100.247]ANCOVA
90% CI: [85.573, 97.939]ANCOVA
95% CI: [96.044, 101.09]ANCOVA
95% CI: [93.319, 99.29]ANCOVA
95% CI: [96.589, 108.525]ANCOVA
90% CI: [93.832, 100.662]ANCOVA
95% CI: [96.56, 103.594]ANCOVA
90% CI: [85.835, 101.238]ANCOVA
90% CI: [98.574, 104.196]ANCOVA
90% CI: [97.324, 102.864]ANCOVA
Primary
AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets
AUC=Area under the concentration-time curve
Time frame: Days 1, 2, and 3 of Periods 1 and 2
Population: Participants who received study medication and were evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (individual tablets) | 5816 pg*h/mL | Standard Deviation 1859 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (FDC) | 5386 pg*h/mL | Standard Deviation 1896 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (individual tablets) | 106070 pg*h/mL | Standard Deviation 26733 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (FDC) | 103865 pg*h/mL | Standard Deviation 31088 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (individual tablets) | 320743 pg*h/mL | Standard Deviation 68176 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (FDC) | 331332 pg*h/mL | Standard Deviation 67491 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (FDC) | 292515 pg*h/mL | Standard Deviation 45404 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (FDC) | 109345 pg*h/mL | Standard Deviation 23947 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (individual tablets) | 5071 pg*h/mL | Standard Deviation 821 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (individual tablets) | 110285 pg*h/mL | Standard Deviation 22139 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (FDC) | 4701 pg*h/mL | Standard Deviation 1028 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (individual tablets) | 305354 pg*h/mL | Standard Deviation 53254 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (FDC) | 8500 pg*h/mL | Standard Deviation 2713 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (individual tablets) | 102913 pg*h/mL | Standard Deviation 22067 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (FDC) | 99215 pg*h/mL | Standard Deviation 20146 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (FDC) | 323039 pg*h/mL | Standard Deviation 56031 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (individual tablets) | 324163 pg*h/mL | Standard Deviation 59358 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (individual tablets) | 8174 pg*h/mL | Standard Deviation 2394 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (individual tablets) | 9628 pg*h/mL | Standard Deviation 3270 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin AUC(0-T) (FDC) | 8936 pg*h/mL | Standard Deviation 2696 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (FDC) | 8936 pg*h/mL | Standard Deviation 2696 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (FDC) | 127232 pg*h/mL | Standard Deviation 28709 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin AUC(0-T) (individual tablets) | 9628 pg*h/mL | Standard Deviation 3270 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin AUC(0-T) (individual tablets) | 124536 pg*h/mL | Standard Deviation 24794 |
90% CI: [82.596, 101.38]ANCOVA
90% CI: [93.889, 101.119]ANCOVA
90% CI: [93.35, 100.316]ANCOVA
90% CI: [85.56, 98.035]ANCOVA
90% CI: [96.028, 101.095]ANCOVA
90% CI: [93.286, 99.286]ANCOVA
90% CI: [96.956, 109.407]ANCOVA
95% CI: [93.778, 100.613]ANCOVA
90% CI: [96.512, 103.648]ANCOVA
90% CI: [85.502, 101.053]ANCOVA
95% CI: [98.494, 104.147]ANCOVA
90% CI: [97.367, 102.932]ANCOVA
Primary
Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets
Time frame: Days 1, 2, and 3 of Periods 1 and 2
Population: Participants who received study medication and were evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (individual tablet) | 713 μg/mL | Standard Deviation 176 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (FDC) | 678 μg/mL | Standard Deviation 167 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (individual tablet) | 29274 μg/mL | Standard Deviation 10209 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (FDC) | 31372 μg/mL | Standard Deviation 11367 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (individual tablets) | 54709 μg/mL | Standard Deviation 16816 |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (FDC) | 56413 μg/mL | Standard Deviation 15775 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (FDC) | 11316 μg/mL | Standard Deviation 45404 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (FDC) | 28140 μg/mL | Standard Deviation 8311 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (individual tablet) | 654 μg/mL | Standard Deviation 118 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (individual tablet) | 28339 μg/mL | Standard Deviation 7339 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (FDC) | 577 μg/mL | Standard Deviation 95 |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (individual tablets) | 52628 μg/mL | Standard Deviation 12850 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (FDC) | 1139 μg/mL | Standard Deviation 325 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (individual tablet) | 30914 μg/mL | Standard Deviation 7965 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (FDC) | 33549 μg/mL | Standard Deviation 7813 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (FDC) | 59878 μg/mL | Standard Deviation 15959 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (individual tablets) | 56444 μg/mL | Standard Deviation 14731 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (individual tablet) | 1177 μg/mL | Standard Deviation 399 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (individual tablets) | 55177 μg/mL | Standard Deviation 13751 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | 5-OH Saxagliptin Cmax (FDC) | 54521 μg/mL | Standard Deviation 12319 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (FDC) | 1091 μg/mL | Standard Deviation 214 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (FDC) | 29545 μg/mL | Standard Deviation 6006 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Metformin Cmax (individual tablet) | 1077 μg/mL | Standard Deviation 139 |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets | Saxagliptin Cmax (individual tablet) | 31319 μg/mL | Standard Deviation 6270 |
90% CI: [87.618, 103.446]ANCOVA
90% CI: [96.552, 119.924]ANCOVA
90% CI: [96.504, 112.883]
90% CI: [82.368, 94.419]ANCOVA
90% CI: [92.263, 104.451]ANCOVA
90% CI: [91.47, 98.714]ANCOVA
90% CI: [15.55, 99]ANCOVA
90% CI: [102.416, 119.559]ANCOVA
90% CI: [99.826, 113.117]ANCOVA
90% CI: [95.164, 105.139]ANCOVA
95% CI: [89.055, 98.47]ANCOVA
Secondary
Number of Participants With Death as Outcome and Serious Adverse Events (SAEs)
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: Continuously, from screening through Day 1 to within 30 days of drug discontinuation on Day 1
Population: All enrolled participants who receive study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed | Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) | SAEs | 0 Participants |