Trial Outcomes & Findings for Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State (NCT NCT02223065)

Results Overview

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

Day 1-3 (Period 1) and Day 8-10 (Period 2)

Results posted on

2016-04-27

Participant Flow

Open-label, randomized, single-dose, 2-treatment, 2-period crossover study in 36 healthy subjects. A single dose was administered on Day 1 and Day 8 under fasted conditions. Blood samples for the plasma pharmacokinetic analysis collected over a 60-hour interval after dosing in each period

Participant milestones

Participant milestones
Measure	Treatment AB Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions. Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.	Treatment BA Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions. Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.
Overall Study STARTED	18	18
Overall Study COMPLETED	18	18
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment AB n=18 Participants Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions. Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.	Treatment BA n=18 Participants Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions. Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.	Total n=36 Participants Total of all reporting groups
Age, Continuous	33.6 YEARS STANDARD_DEVIATION 11.63 • n=5 Participants	32.9 YEARS STANDARD_DEVIATION 11.34 • n=7 Participants	33.3 YEARS STANDARD_DEVIATION 11.32 • n=5 Participants
Age, Customized < 65	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized BLACK/AFRICAN AMERICAN	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized WHITE	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1-3 (Period 1) and Day 8-10 (Period 2)

Population: Evaluable PK Population

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Outcome measures

Outcome measures
Measure	Treatment A n=36 Participants Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.	Treatment B n=36 Participants Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.
Saxagliptin Maximum Observed Concentrations (Cmax)	26.2 ng/mL 90% Confidence Interval 5.723 • Interval 24.6 to 27.8	25.5 ng/mL 90% Confidence Interval 5.763 • Interval 24.0 to 27.1

PRIMARY outcome

Timeframe: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)

Population: Evaluable PK Population

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Outcome measures

Outcome measures
Measure	Treatment A n=36 Participants Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.	Treatment B n=36 Participants Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.
Dapagliflozin Maximum Observed Concentrations (Cmax)	142 ng/mL 90% Confidence Interval 28.93 • Interval 132.0 to 153.0	141 ng/mL 90% Confidence Interval 37.10 • Interval 132.0 to 152.0

PRIMARY outcome

Timeframe: Day 1-3 (Period 1) and Day 8-10 (Period 2)

Population: Evaluable PK Population

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Outcome measures

Outcome measures
Measure	Treatment A n=36 Participants Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.	Treatment B n=36 Participants Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.
Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])	95.9 ng.h/mL 90% Confidence Interval 5.723 • Interval 90.0 to 102.0	98.0 ng.h/mL 90% Confidence Interval 5.763 • Interval 92.0 to 104.0

PRIMARY outcome

Timeframe: Day 1-3 (Period 1) and Day 8-10 (Period 2)

Population: Evaluable PK Population

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Outcome measures

Outcome measures
Measure	Treatment A n=36 Participants Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.	Treatment B n=36 Participants Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.
Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])	537 ng.h/mL 90% Confidence Interval 5.723 • Interval 504.0 to 573.0	546 ng.h/mL 90% Confidence Interval 5.763 • Interval 512.0 to 582.0

PRIMARY outcome

Timeframe: Day 1-3 (Period 1) and Day 8-10 (Period 2)

Population: Evaluable PK Population

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Outcome measures

Outcome measures
Measure	Treatment A n=36 Participants Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.	Treatment B n=36 Participants Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.
Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])	97.0 ng.h/mL 90% Confidence Interval 5.723 • Interval 91.1 to 103.0	99.4 ng.h/mL 90% Confidence Interval 5.763 • Interval 93.3 to 106.0

PRIMARY outcome

Timeframe: Day 1-3 (Period 1) and Day 8-10 (Period 2)

Population: Evaluable PK Population

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Outcome measures

Outcome measures
Measure	Treatment A n=36 Participants Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.	Treatment B n=36 Participants Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.
Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])	553 ng.h/mL 90% Confidence Interval 5.723 • Interval 518.0 to 591.0	561 ng.h/mL 90% Confidence Interval 5.763 • Interval 525.0 to 599.0

Adverse Events

Treatment A

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment B

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Eva Johnsson, Clinical Science Lead, GLOBAL_MEDICINES_DEV

AstraZeneca AB, S-151 85 Södertälje, Sweden

Phone: +46 31 7762484

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place