Trial Outcomes & Findings for Bioequivalence Study of Fixed-dose Combinations and Coadministered Individual Tablets of Saxagliptin/Metformin-Brazil (NCT NCT01365091)

NCT ID: NCT01365091

Last Updated: 2015-05-08

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

112 participants

Primary outcome timeframe

Days 1, 2, and 3 of Periods 1 and 2

Results posted on

2015-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	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).	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).	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).	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).
Period 1 STARTED	28	28	28	28
Period 1 COMPLETED	26	26	25	25
Period 1 NOT COMPLETED	2	2	3	3
Period 2 STARTED	26	26	25	25
Period 2 COMPLETED	25	26	24	25
Period 2 NOT COMPLETED	1	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).	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).	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).
Period 1 Adverse Event	1	0	2	3
Period 1 Positive test result for drugs of abuse	1	0	0	0
Period 1 No longer met study criteria	0	1	0	0
Period 1 Withdrawal by Subject	0	1	0	0
Period 1 Personal reasons	0	0	1	0
Period 2 Withdrawal by Subject	1	0	0	0
Period 2 Adverse Event	0	0	1	0

Baseline Characteristics

Bioequivalence Study of Fixed-dose Combinations and Coadministered Individual Tablets of Saxagliptin/Metformin-Brazil

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Treatments A/B, B/A n=28 Participants 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).	Arm 2: Treatments C/D, D/C n=28 Participants 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).	Arm 3:Treatments E/ F, F/E n=28 Participants 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).	Arm 4: Treatments G/ H, H/G n=28 Participants 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).	Total n=112 Participants Total of all reporting groups
Age, Customized <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Customized Between 18 and 55 years	28 Participants n=5 Participants	28 Participants n=7 Participants	28 Participants n=5 Participants	28 Participants n=4 Participants	112 Participants n=21 Participants
Age, Customized >=55 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex/Gender, Customized Both genders	28 Participants n=5 Participants	28 Participants n=7 Participants	28 Participants n=5 Participants	28 Participants n=4 Participants	112 Participants n=21 Participants

PRIMARY outcome

Timeframe: Days 1, 2, and 3 of Periods 1 and 2

Population: Participants who received study medication and were evaluable

Outcome measures

Outcome measures
Measure	Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted n=25 Participants Arm 1: Treatments A, B/B, A. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 500-mg extended-release (XR) 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 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).	Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed n=26 Participants Arm 2: Treatment C, D/D, C. Period 1: Participants received a single oral dose of saxagliptin (sax) 5-mg/metformin (met) 500-mg, extended-release (XR) 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 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 metformin XR, 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 XR FDC, in the fed state (Treatment C).	Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted n=24 Participants Arm 3: Treatment E, F/F, G. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 1000-mg extended-release (XR) 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 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).	Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed n=25 Participants Arm 4: Treatments G,H/H,G. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 1000-mg extended-release (XR) 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 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).
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 • Interval 87.618 to 103.446	654 μg/mL Standard Deviation 118 • Interval 82.368 to 94.419	1177 μg/mL Standard Deviation 399 • Interval 90.376 to 105.404	1077 μg/mL Standard Deviation 139 • Interval 95.164 to 105.139
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	577 μg/mL Standard Deviation 95	1139 μg/mL Standard Deviation 325	1091 μg/mL Standard Deviation 214
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 • Interval 96.552 to 119.924	28339 μg/mL Standard Deviation 7339 • Interval 92.263 to 104.451	30914 μg/mL Standard Deviation 7965 • Interval 96.956 to 109.407	31319 μg/mL Standard Deviation 6270 • Interval 89.055 to 98.47
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	28140 μg/mL Standard Deviation 8311	33549 μg/mL Standard Deviation 7813	29545 μg/mL Standard Deviation 6006
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 • Interval 96.504 to 112.883	52628 μg/mL Standard Deviation 12850 • Interval 91.47 to 98.714	56444 μg/mL Standard Deviation 14731 • Interval 96.589 to 108.52	55177 μg/mL Standard Deviation 13751 • Interval 95.572 to 103.144
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	11316 μg/mL Standard Deviation 45404	59878 μg/mL Standard Deviation 15959	54521 μg/mL Standard Deviation 12319

PRIMARY outcome

Timeframe: Days 1, 2, and 3 of Periods 1 and 2

Population: Participants who received study medication and were evaluable

AUC=Area under the concentration-time curve

Outcome measures

Outcome measures
Measure	Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted n=25 Participants Arm 1: Treatments A, B/B, A. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 500-mg extended-release (XR) 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 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).	Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed n=26 Participants Arm 2: Treatment C, D/D, C. Period 1: Participants received a single oral dose of saxagliptin (sax) 5-mg/metformin (met) 500-mg, extended-release (XR) 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 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 metformin XR, 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 XR FDC, in the fed state (Treatment C).	Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted n=24 Participants Arm 3: Treatment E, F/F, G. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 1000-mg extended-release (XR) 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 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).	Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed n=25 Participants Arm 4: Treatments G,H/H,G. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 1000-mg extended-release (XR) 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 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).
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 • Interval 82.596 to 101.38	5071 pg*h/mL Standard Deviation 821 • Interval 85.56 to 98.035	8174 pg*h/mL Standard Deviation 2394 • Interval 96.956 to 109.407	9628 pg*h/mL Standard Deviation 3270 • Interval 85.502 to 101.053
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	4701 pg*h/mL Standard Deviation 1028	8500 pg*h/mL Standard Deviation 2713	8936 pg*h/mL Standard Deviation 2696
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	110285 pg*h/mL Standard Deviation 22139	102913 pg*h/mL Standard Deviation 22067	124536 pg*h/mL Standard Deviation 24794 • Interval 98.494 to 104.147
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	109345 pg*h/mL Standard Deviation 23947	99215 pg*h/mL Standard Deviation 20146	127232 pg*h/mL Standard Deviation 28709
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	305354 pg*h/mL Standard Deviation 53254	324163 pg*h/mL Standard Deviation 59358	9628 pg*h/mL Standard Deviation 3270
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	292515 pg*h/mL Standard Deviation 45404	323039 pg*h/mL Standard Deviation 56031 • Interval 96.512 to 103.648	8936 pg*h/mL Standard Deviation 2696 • Interval 97.367 to 102.932

PRIMARY outcome

Timeframe: Days 1, 2, and 3 of Periods 1 and 2

Population: Participants who received study medication and were evaluable

AUC=Area Under the Concentration-time Curve

Outcome measures

Outcome measures
Measure	Sax, 5 mg/Met 500 mg XR FDC vs Individual Tablets, Fasted n=25 Participants Arm 1: Treatments A, B/B, A. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 500-mg extended-release (XR) 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 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).	Sax, 5 mg/Met 500 mg vs FDC to Individual Tablets, Fed n=26 Participants Arm 2: Treatment C, D/D, C. Period 1: Participants received a single oral dose of saxagliptin (sax) 5-mg/metformin (met) 500-mg, extended-release (XR) 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 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 metformin XR, 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 XR FDC, in the fed state (Treatment C).	Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fasted n=24 Participants Arm 3: Treatment E, F/F, G. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 1000-mg extended-release (XR) 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 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).	Sax, 5 mg/Met 1000 mg XR FDC to Individual Tablets, Fed n=25 Participants Arm 4: Treatments G,H/H,G. Period 1: Participants received a single oral dose of saxagliptin (sax), 5-mg/metformin (met), 1000-mg extended-release (XR) 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 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).
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 • Interval 93.393 to 100.247	310983 ng*h/mL Standard Deviation 53447 • Interval 93.319 to 99.29	330247 ng*h/mL Standard Deviation 59863 • Interval 96.56 to 103.594	332495 ng*h/mL Standard Deviation 62192 • Interval 97.324 to 102.864
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	5127 ng*h/mL Standard Deviation 816	8338 ng*h/mL Standard Deviation 2414	9731 ng*h/mL Standard Deviation 3277
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 • Interval 82.697 to 101.226	4754 ng*h/mL Standard Deviation 1037 • Interval 85.573 to 97.939	8618 ng*h/mL Standard Deviation 2726 • Interval 96.589 to 108.525	9054 ng*h/mL Standard Deviation 2684 • Interval 85.835 to 101.238
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 • Interval 93.955 to 101.132	111677 ng*h/mL Standard Deviation 22315 • Interval 96.044 to 101.09	104293 ng*h/mL Standard Deviation 22149 • Interval 93.832 to 100.662	125820 ng*h/mL Standard Deviation 24856 • Interval 98.574 to 104.196
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	110705 ng*h/mL Standard Deviation 24091	100620 ng*h/mL Standard Deviation 20264	128602 ng*h/mL Standard Deviation 28729
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	298037 ng*h/mL Standard Deviation 45636	329085 ng*h/mL Standard Deviation 56298	332869 ng*h/mL Standard Deviation 59469

SECONDARY outcome

Timeframe: Continuously, from screening through Day 1 to within 30 days of drug discontinuation on Day 1

Population: All enrolled participants who receive study medication

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.