Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to evaluate whether the pharmacokinetics (body concentrations/metabolism of the drug) of Saxagliptin and Dapagliflozin are affected when they are administered together
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin) | Experimental | Treatment A: Saxagliptin 5mg, Tablet, Oral; Single dose Treatment B: Dapagliflozin 10mg, Tablet, Oral; single dose Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; single dose |
|
| A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-Dapagliflozin | Experimental | Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment B: Dapagliflozin 10mg, Tablet, Oral, single dose |
|
| B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin) | Experimental | Treatment B: Dapagliflozin 10mg, Tablet, Oral, single dose. Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose |
|
| B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin | Experimental | Treatment B: Dapagliflozin 10mg, Tablet, Oral, single dose; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saxagliptin | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin From a Single Dose of Dapagliflozin Versus Cmax of Dapagliflozin From Co-administered Saxagliptin Plus Dapagliflozin - Pharmacokinetic Evaluable Population | The geometric mean of the maximum observed plasma concentration (Cmax) is presented below; serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h,and 60 h postdose, relative to dosing on Day 1 in each cross over period and these data are summarized in the Pharmacokinetic (PK) parameter of Cmax presented here. Plasma samples were analyzed for dapagliflozin by High Performance Liquid chromatography-Mass Spectrometry (HPLC-MS/MS) using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Dapagliflozin Cmax was derived from plasma concentration versus time data using a non-compartmental method, using a validated PK analysis program ™. Actual sampling times were used for PK calculations. Cmax was reported in ng/mL. | Day 1 (0 h to 60 h post dose) in each period |
| Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity [AUC(INF)] of Dapagliflozin From a Single Dose of Dapagliflozin Versus AUC (INF) of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population | AUC(INF) is area under the plasma concentration-time curve from time 0 extrapolated to infinity. Serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(INF) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | Day 1 (0h to 60h post dose) in each period |
| Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus AUC(0-T) for Dapagliflozin When Co-administered With 5 mg Saxagliptin |
| Measure | Description | Time Frame |
|---|---|---|
| Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus Tmax of Dapagliflozin When Co-administered With 5 mg Saxagliptin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method. Actual sampling times were used for PK calculations. Tmax was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icon Clinical Pharmacology | Omaha | Nebraska | 68154 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27491280 | Derived | Vakkalagadda B, Lubin S, Reynolds L, Liang D, Marion AS, LaCreta F, Boulton DW. Lack of a Pharmacokinetic Interaction Between Saxagliptin and Dapagliflozin in Healthy Subjects: A Randomized Crossover Study. Clin Ther. 2016 Aug;38(8):1890-9. doi: 10.1016/j.clinthera.2016.07.005. Epub 2016 Aug 2. |
Not provided
Not provided
89 participants enrolled; 42 randomized and treated with study drug. 47 not randomized for following reasons: 3 withdrew consent, 38 no longer met study criteria, 6 had other reasons. Treatment was administered on Day 1 of each period after fast of 10 hours; Washout began after single dose in the period and was for at least 6 days.
20 August 2012 to 29 November 2012. Phase 1 Clinical Pharmacology center with healthy, fasted participants.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin) | Single dose of: Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral |
| FG001 | A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-Dapagliflozin | Single dose of: Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral |
| FG002 | B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin) | Single dose of: Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral |
| FG003 | B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin | Single dose of: Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral |
| FG004 | C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin | Single dose of: Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral |
| FG005 | C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin | Single dose of: Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Period 2 |
| |||||||||||||
| Period 3 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin) | Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral. |
| BG001 | A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-Dapagliflozin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin From a Single Dose of Dapagliflozin Versus Cmax of Dapagliflozin From Co-administered Saxagliptin Plus Dapagliflozin - Pharmacokinetic Evaluable Population | The geometric mean of the maximum observed plasma concentration (Cmax) is presented below; serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h,and 60 h postdose, relative to dosing on Day 1 in each cross over period and these data are summarized in the Pharmacokinetic (PK) parameter of Cmax presented here. Plasma samples were analyzed for dapagliflozin by High Performance Liquid chromatography-Mass Spectrometry (HPLC-MS/MS) using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Dapagliflozin Cmax was derived from plasma concentration versus time data using a non-compartmental method, using a validated PK analysis program ™. Actual sampling times were used for PK calculations. Cmax was reported in ng/mL. | Pharmacokinetic (PK) Evaluable: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 (0 h to 60 h post dose) in each period |
Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A: Saxagliptin 5mg | Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 15.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boaz Hirschberg | AstraZeneca Pharmaceuticals | ClinicalTrialTransparency@astrazeneca.com |
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C502994 | saxagliptin |
| C529054 | dapagliflozin |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin |
| Experimental |
Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose; Treatment B: Dapagliflozin 10mg, Tablet, Oral, single dose |
|
| C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin | Experimental | Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, single dose; Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose |
|
|
| Dapagliflozin | Drug |
|
|
AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method). Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(0-T) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). |
| Day 1 (0h to 60h post dose) in each period |
| Maximum Observed Concentration (Cmax) of a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). Cmax for Saxagliptin was derived from plasma concentration versus time data using a validated PK analysis program ™ and was measured in nanograms per milliliter (ng/mL). | Day 1 (0h to 60h post dose) in each period |
| AUC(0-T) of Saxagliptin From Single Dose 5 mg Saxagliptin Versus AUC(0-T) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(0-T), the area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | Day 1 (0h to 60h post dose) in each period |
| AUC(INF) of Saxagliptin From a Single Dose of 5 mg Saxagliptin Versus AUC(INF) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(INF) was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | Day 1 (0h to 60h post dose) in each period |
| Day 1 (0h to 60h post dose) in each period |
| Half-life (T-HALF) of Dapagliflozin From a Single Dose of Dapagliflozin Versus T-Half of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method. Actual sampling times were used for PK calculations. T-HALF was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours. | Day 1 (0h to 60h post dose) in each period |
| Plasma Apparent Clearance (CLT/F) of a Single Dose of Dapagliflozin Versus CLT/F of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method. Actual sampling times were used for PK calculations. CLT/F was calculated as Dose/AUC(INF)and was measured in milliliters per minute (mL/min). | Day 1 (0h to 60h post dose) in each period |
| Cmax of 5-Hydroxy (5-OH) Saxagliptin From a Single Dose Saxagliptin Versus Cmax of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). Actual sampling times were used for PK calculations. Cmax for 5-OH Saxagliptin (the major active metabolite of Saxagliptin) was derived from plasma concentration versus time data using a validated PK analysis program ™ and was measured in ng/mL. | Day 1 (0h to 60h post dose) in each period |
| AUC(0-T) of 5-OH Saxagliptin From Single Dose Saxagliptin Versus AUC(0-T) of 5-OH From Saxagliptin Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method)and was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™. AUC (0-T) was measured in nanograms*hours per milliliter (ng*h/mL). | Day 1 (0h to 60h post dose) in each period |
| AUC(INF) of 5-OH Saxagliptin From a Single Dose Saxagliptin Versus AUC(INF) of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). AUC(INF) was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | Day 1 (0h to 60h post dose) in each period |
| Cmax of the Saxagliptin Total Active Moiety From a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Cmax of saxagliptin total active moiety (molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin) was derived from the plasma concentration versus time profile for the saxagliptin total active moiety. Measurement was in nano Molars (nM). | Day 1 (0h to 60h post dose) in each period |
| AUC(INF) and AUC(0-T) of the Saxagliptin Total Active Moiety From a Single Dose 5 mg Saxagliptin Versus AUC(INF) and AUC(0-T) of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method. AUC(INF) is area under the plasma concentration-time curve from time zero extrapolated to infinity; AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method) and both were derived from the plasma concentration versus time profile using a validated PK analysis program ™. Total moiety (molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin), AUC(0-T)and AUC(INF) were measured in nano Molars*hours (nM*h). | Day 1 (0h to 60h post dose) in each period |
| Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin and 5-OH by LC-MS/MS using a validated method. Tmax was derived from the plasma concentration versus time profile for study drug and was measured in hours (h). Saxagliptin was the drug, 5-OH saxagliptin was the metabolite, and Saxagliptin total Active Moiety was molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin. | Day 1 (0h to 60h post dose) in each period |
| Half-life (T-HALF) of Saxagliptin, and 5-OH Saxagliptin From Single Dose 5 mg Saxagliptin Versus T-HALF of Saxagliptin and 5-OH From Co-administered Saxagliptin With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method. T-HALF was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours (h). | Day 1 (0h to 60h post dose) in each period |
| Metabolite to Parent Molar Ratios (MR) of Cmax, AUC(INF), and AUC(0-T) of 5-OH Saxagliptin and Saxagliptin From a Single Dose 5 mg Saxagliptin Versus MR of Saxagliptin and 5-OH When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Saxagliptin is the parent drug and 5-OH saxagliptin is the metabolite. The molecular weights to be used for the molar ratios were 315.42 and 331.42 for saxagliptin and 5-OH, respectively. Plasma samples were analyzed for saxagliptin and for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL and 0.200 ng/mL to 100.0 ng/mL for saxagliptin and 5-OH, respectively). | Day 1 (0h to 60h post dose) in each period |
| Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population | Adverse event (AE)=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. End of study was approximately 16 days and was the time for a participant to conclude each of the 3 periods (including the 6 day washout between periods). | Day 1 to end of study (16 days) |
| Number of Participants With Marked Hematology Laboratory Abnormalities - Safety Population | Fasted for 10 hours prior to samples taken. Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Lower limit of normal (LLN); upper limit of normal (ULN); pretreatment(pre-RX); treatment (RX). Hemoglobin (g/L): <0.85* pre-RX; hematocrit (vol): <0.85*pre-RX; erythrocytes (*10^12 c/L): <0.85*pre-RX; platelet count (*10^9 c/L): <0.85*LLN if pre-RX>=LLN, or if Pre-Tx <LLN; leukocytes (*10^9 c/L): <0.85*LLN if pre-RX <LLN,or <0.9*LLN if LLN<=Pre-RX<=ULN; neutrophils+bands (*10^9 c/L): <0.85*Pre-RX if Pre-RX <1.5 or <1.5 if Pre-RX >=1.5; eosinophils (*10^9 c/L): if value >0.75; basophils (*10^9 c/L): if value >0.4; monocytes (*10^9c/L): if value >2; lymphocytes (*10^9 c/L): if value <0.750 or if value >7.50. | Baseline to Day 1 of each period |
| Mean Change From Baseline in Systolic and Diastolic Blood Pressure - Safety Population | Blood pressure was taken while the participant was quietly seated for at least 5 minutes. Blood pressure was measured in millimeters of mercury (mmHg). Baseline was Day -1 in Period 1; study drug was administered on Day 1 of each crossover period. | Baseline to Day 1 of each period |
| Mean Change From Baseline in Heart Rate - Safety Population | Heart rates were taken while the participant was sitting quietly for at least 5 minutes and were measured in beats per minute (bpm). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. | Baseline to Day 1 in each period |
| Mean Change From Baseline in Respiration Rate - Safety Population | Respiration rates were taken while the participant was sitting quietly for at least 5 minutes and were measured in breaths per minute (bpm). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. | Baseline to Day 1 in each period |
| Mean Change From Baseline in Temperature - Safety Population | Participant had their temperature taken after quietly sitting for at least 5 minutes and it was measured as degrees of centigrade (C). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. | Baseline to Day 1 in each period |
| Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population | Fasted for 10 hours prior to samples taken. Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Lower limit of normal(LLN); upper limit of normal (ULN); pre-treatment(Pre-Rx). Alkaline phosphatase U/L:>1.25*Pre-RX if Pre-Rx >ULN or >1.25*ULN if Pre-Rx <=ULN; aspartate aminotransferase (AST) U/L: >1.25*Pre-Rx if Pre-Rx > ULN or 1.25*ULN if Pre-Rx <= ULN;alanine aminotransferase (ALT) U/L: >1.25*Pre-Rx if Pre-Rx>ULN or 1.25*ULN if Pre-Rx<=ULN;blood urea nitrogen (BUN)mmol/L: >1.1*ULN if Pre-Rx <=ULN or >1.2*Pre-Rx if Pre-Rx >ULN; total bilirubin µmol/L: >1.1*ULN if Pre-Rx <=ULN or >1.25*Pre-Rx if Pre-Rx >ULN;direct bilirubin µmol/L: >1.1*ULN if Pre-Rx <= ULN or >1.25*Pre-Rx if Pre-Rx > ULN; creatine phosphokinase (CK) U/L: >1.5*Pre-Rx if Pre-Rx >ULN or >1.5*ULN if Pre-Rx <= ULN. | Baseline to Day 1 in each period |
| Number of Participants With Marked Urinalysis Laboratory Abnormalities - Safety Population | Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Fasted for 10 hours prior to samples taken. LLN=lower limit of normal; ULN=upper limit of normal; pretreatment (Pre-Rx). Normals: Urine glucose qualitative: dipstick >=1 if Pre-Rx <1 or 2*Pre-Rx if Pre-Rx>=1; urine microscopic white blood cell count (WBC): >=2 if Pre-Rx <2 or >=4 if Pre-Rx >=2;urine red blood cell count (RBC):>=2 if Pre-Rx <2 or >=4 if Pre-Rx >=2. | Baseline to Day 1 of each period |
| Number of Participants With Change From Baseline in ECG Interval - Safety Population | A 12-Lead electrocardiogram (ECG) was performed and recorded after the participant had been supine for at least 5 minutes. ECGs done at baseline (Day-1 of Period 1) and at end of study; therefore the results are presented by sequence, and cannot be presented by treatment. QT interval (measure between Q wave and T wave in the heart's electrical cycle); and QT interval corrected for heart rate using Fridericia's formula (QTcF) were measured in milliseconds (msec). Abnormality criteria: QT/QTcF QT or QTcF >450 msec and <=480 msec at any postdose time point and not present at baseline. QT or QTcF >480 msec and <=500 msec at any postdose time point and not present at baseline QT or QTcF >500 msec at any postdose time point and not present at baseline. QT/QTcF Increase from baseline >60 msec for at least 1 postdose measurement. Increase from baseline in QT or QTcF >30 msec for at least 1 postdose measurement, but <=60 msec for all postdose measurements. | Baseline to end of study (16 days) |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral. |
| BG002 | B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin) | Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral |
| BG003 | B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin | Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral. |
| BG004 | C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin | Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral. |
| BG005 | C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin | Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral. |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Surface Area (m^2) | Body surface area was measured in meters squared (m^2) prior to first dose of study drug (Day -1). | Mean | Standard Deviation | m^2 |
|
| Body Weight (kg) | Body weight was measured in kilograms (k) prior to first dose of study drug (Day -1). | Mean | Standard Deviation | kg |
|
|
|
|
|
| Primary | Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity [AUC(INF)] of Dapagliflozin From a Single Dose of Dapagliflozin Versus AUC (INF) of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population | AUC(INF) is area under the plasma concentration-time curve from time 0 extrapolated to infinity. Serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(INF) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus Tmax of Dapagliflozin When Co-administered With 5 mg Saxagliptin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method. Actual sampling times were used for PK calculations. Tmax was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours. | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. 1 participant (ACB treatment sequence) withdrew consent after having received all 3 treatments and did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). This did not impact T-HALF. | Posted | Median | Full Range | hours | Day 1 (0h to 60h post dose) in each period |
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus AUC(0-T) for Dapagliflozin When Co-administered With 5 mg Saxagliptin | AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method). Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(0-T) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | Half-life (T-HALF) of Dapagliflozin From a Single Dose of Dapagliflozin Versus T-Half of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method. Actual sampling times were used for PK calculations. T-HALF was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours. | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. 1 participant (ACB treatment sequence) withdrew consent after having received all 3 treatments and did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). This did not impact T-HALF. | Posted | Mean | Standard Deviation | hours | Day 1 (0h to 60h post dose) in each period |
|
|
|
| Primary | Maximum Observed Concentration (Cmax) of a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). Cmax for Saxagliptin was derived from plasma concentration versus time data using a validated PK analysis program ™ and was measured in nanograms per milliliter (ng/mL). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | Plasma Apparent Clearance (CLT/F) of a Single Dose of Dapagliflozin Versus CLT/F of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method. Actual sampling times were used for PK calculations. CLT/F was calculated as Dose/AUC(INF)and was measured in milliliters per minute (mL/min). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Day 1 (0h to 60h post dose) in each period |
|
|
|
| Secondary | Cmax of 5-Hydroxy (5-OH) Saxagliptin From a Single Dose Saxagliptin Versus Cmax of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). Actual sampling times were used for PK calculations. Cmax for 5-OH Saxagliptin (the major active metabolite of Saxagliptin) was derived from plasma concentration versus time data using a validated PK analysis program ™ and was measured in ng/mL. | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Primary | AUC(0-T) of Saxagliptin From Single Dose 5 mg Saxagliptin Versus AUC(0-T) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(0-T), the area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Primary | AUC(INF) of Saxagliptin From a Single Dose of 5 mg Saxagliptin Versus AUC(INF) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(INF) was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | AUC(0-T) of 5-OH Saxagliptin From Single Dose Saxagliptin Versus AUC(0-T) of 5-OH From Saxagliptin Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method)and was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™. AUC (0-T) was measured in nanograms*hours per milliliter (ng*h/mL). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | AUC(INF) of 5-OH Saxagliptin From a Single Dose Saxagliptin Versus AUC(INF) of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). AUC(INF) was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in nanograms*hours per milliliter (ng*h/mL). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | Cmax of the Saxagliptin Total Active Moiety From a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Cmax of saxagliptin total active moiety (molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin) was derived from the plasma concentration versus time profile for the saxagliptin total active moiety. Measurement was in nano Molars (nM). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | AUC(INF) and AUC(0-T) of the Saxagliptin Total Active Moiety From a Single Dose 5 mg Saxagliptin Versus AUC(INF) and AUC(0-T) of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method. AUC(INF) is area under the plasma concentration-time curve from time zero extrapolated to infinity; AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method) and both were derived from the plasma concentration versus time profile using a validated PK analysis program ™. Total moiety (molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin), AUC(0-T)and AUC(INF) were measured in nano Molars*hours (nM*h). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM*h | Day 1 (0h to 60h post dose) in each period |
|
|
|
|
| Secondary | Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin and 5-OH by LC-MS/MS using a validated method. Tmax was derived from the plasma concentration versus time profile for study drug and was measured in hours (h). Saxagliptin was the drug, 5-OH saxagliptin was the metabolite, and Saxagliptin total Active Moiety was molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin. | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Median | Full Range | h | Day 1 (0h to 60h post dose) in each period |
|
|
|
| Secondary | Half-life (T-HALF) of Saxagliptin, and 5-OH Saxagliptin From Single Dose 5 mg Saxagliptin Versus T-HALF of Saxagliptin and 5-OH From Co-administered Saxagliptin With 10 mg Dapagliflozin - PK Evaluable Population | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method. T-HALF was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours (h). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Mean | Standard Deviation | h | Day 1 (0h to 60h post dose) in each period |
|
|
|
| Secondary | Metabolite to Parent Molar Ratios (MR) of Cmax, AUC(INF), and AUC(0-T) of 5-OH Saxagliptin and Saxagliptin From a Single Dose 5 mg Saxagliptin Versus MR of Saxagliptin and 5-OH When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable | Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Saxagliptin is the parent drug and 5-OH saxagliptin is the metabolite. The molecular weights to be used for the molar ratios were 315.42 and 331.42 for saxagliptin and 5-OH, respectively. Plasma samples were analyzed for saxagliptin and for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL and 0.200 ng/mL to 100.0 ng/mL for saxagliptin and 5-OH, respectively). | PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | Molar ratio | Day 1 (0h to 60h post dose) in each period |
|
|
|
| Secondary | Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population | Adverse event (AE)=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. End of study was approximately 16 days and was the time for a participant to conclude each of the 3 periods (including the 6 day washout between periods). | Safety Population = All participants who received at least one dose of any study drug. | Posted | Number | participants | Day 1 to end of study (16 days) |
|
|
|
| Secondary | Number of Participants With Marked Hematology Laboratory Abnormalities - Safety Population | Fasted for 10 hours prior to samples taken. Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Lower limit of normal (LLN); upper limit of normal (ULN); pretreatment(pre-RX); treatment (RX). Hemoglobin (g/L): <0.85* pre-RX; hematocrit (vol): <0.85*pre-RX; erythrocytes (*10^12 c/L): <0.85*pre-RX; platelet count (*10^9 c/L): <0.85*LLN if pre-RX>=LLN, or if Pre-Tx <LLN; leukocytes (*10^9 c/L): <0.85*LLN if pre-RX <LLN,or <0.9*LLN if LLN<=Pre-RX<=ULN; neutrophils+bands (*10^9 c/L): <0.85*Pre-RX if Pre-RX <1.5 or <1.5 if Pre-RX >=1.5; eosinophils (*10^9 c/L): if value >0.75; basophils (*10^9 c/L): if value >0.4; monocytes (*10^9c/L): if value >2; lymphocytes (*10^9 c/L): if value <0.750 or if value >7.50. | Safety Population = All participants who received at least one dose of any study drug. | Posted | Number | participants | Baseline to Day 1 of each period |
|
|
|
| Secondary | Mean Change From Baseline in Systolic and Diastolic Blood Pressure - Safety Population | Blood pressure was taken while the participant was quietly seated for at least 5 minutes. Blood pressure was measured in millimeters of mercury (mmHg). Baseline was Day -1 in Period 1; study drug was administered on Day 1 of each crossover period. | Safety Population = All participants who received at least one dose of any study drug. | Posted | Mean | Standard Deviation | mmHg | Baseline to Day 1 of each period |
|
|
|
| Secondary | Mean Change From Baseline in Heart Rate - Safety Population | Heart rates were taken while the participant was sitting quietly for at least 5 minutes and were measured in beats per minute (bpm). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. | Safety Population = All participants who received at least one dose of any study drug. | Posted | Mean | Standard Deviation | bpm | Baseline to Day 1 in each period |
|
|
|
| Secondary | Mean Change From Baseline in Respiration Rate - Safety Population | Respiration rates were taken while the participant was sitting quietly for at least 5 minutes and were measured in breaths per minute (bpm). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. | Posted | Mean | Standard Deviation | bpm | Baseline to Day 1 in each period |
|
|
|
| Secondary | Mean Change From Baseline in Temperature - Safety Population | Participant had their temperature taken after quietly sitting for at least 5 minutes and it was measured as degrees of centigrade (C). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. | Safety Population = All participants who received at least one dose of any study drug. | Posted | Mean | Standard Deviation | degrees of centigrade | Baseline to Day 1 in each period |
|
|
|
| Secondary | Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population | Fasted for 10 hours prior to samples taken. Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Lower limit of normal(LLN); upper limit of normal (ULN); pre-treatment(Pre-Rx). Alkaline phosphatase U/L:>1.25*Pre-RX if Pre-Rx >ULN or >1.25*ULN if Pre-Rx <=ULN; aspartate aminotransferase (AST) U/L: >1.25*Pre-Rx if Pre-Rx > ULN or 1.25*ULN if Pre-Rx <= ULN;alanine aminotransferase (ALT) U/L: >1.25*Pre-Rx if Pre-Rx>ULN or 1.25*ULN if Pre-Rx<=ULN;blood urea nitrogen (BUN)mmol/L: >1.1*ULN if Pre-Rx <=ULN or >1.2*Pre-Rx if Pre-Rx >ULN; total bilirubin µmol/L: >1.1*ULN if Pre-Rx <=ULN or >1.25*Pre-Rx if Pre-Rx >ULN;direct bilirubin µmol/L: >1.1*ULN if Pre-Rx <= ULN or >1.25*Pre-Rx if Pre-Rx > ULN; creatine phosphokinase (CK) U/L: >1.5*Pre-Rx if Pre-Rx >ULN or >1.5*ULN if Pre-Rx <= ULN. | Safety Population = All participants who received at least one dose of any study drug. | Posted | Number | participants | Baseline to Day 1 in each period |
|
|
|
| Secondary | Number of Participants With Marked Urinalysis Laboratory Abnormalities - Safety Population | Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Fasted for 10 hours prior to samples taken. LLN=lower limit of normal; ULN=upper limit of normal; pretreatment (Pre-Rx). Normals: Urine glucose qualitative: dipstick >=1 if Pre-Rx <1 or 2*Pre-Rx if Pre-Rx>=1; urine microscopic white blood cell count (WBC): >=2 if Pre-Rx <2 or >=4 if Pre-Rx >=2;urine red blood cell count (RBC):>=2 if Pre-Rx <2 or >=4 if Pre-Rx >=2. | Safety Population = All participants who received at least one dose of any study drug. Urine WBC and RBC were not done for all 42 participants. Number of participants analyzed (N) for the 3 treatments for WBC/RBC urine were 4, 8, 6, in treatment A, B, C, respectively. | Posted | Number | participants | Baseline to Day 1 of each period |
|
|
|
| Secondary | Number of Participants With Change From Baseline in ECG Interval - Safety Population | A 12-Lead electrocardiogram (ECG) was performed and recorded after the participant had been supine for at least 5 minutes. ECGs done at baseline (Day-1 of Period 1) and at end of study; therefore the results are presented by sequence, and cannot be presented by treatment. QT interval (measure between Q wave and T wave in the heart's electrical cycle); and QT interval corrected for heart rate using Fridericia's formula (QTcF) were measured in milliseconds (msec). Abnormality criteria: QT/QTcF QT or QTcF >450 msec and <=480 msec at any postdose time point and not present at baseline. QT or QTcF >480 msec and <=500 msec at any postdose time point and not present at baseline QT or QTcF >500 msec at any postdose time point and not present at baseline. QT/QTcF Increase from baseline >60 msec for at least 1 postdose measurement. Increase from baseline in QT or QTcF >30 msec for at least 1 postdose measurement, but <=60 msec for all postdose measurements. | Safety Population = All participants who received at least one dose of any study drug. | Posted | Number | participants | Baseline to end of study (16 days) |
|
|
|
| 0 |
| 42 |
| 6 |
| 42 |
| EG001 | Treatment B: Dapagliflozin 10mg | Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods. | 0 | 42 | 9 | 42 |
| EG002 | Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg | Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods. | 0 | 42 | 8 | 42 |
| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Dysmenorrhea | Reproductive system and breast disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Abdominal Pain Lower | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| ALT increased | Investigations | MedDRA 15.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| D004700 | Endocrine System Diseases |
| Tmax of Saxagliptin Total Active Moiety |
|
| MR_AUC(0-T) |
|
|
| Participants with SAEs |
|
| Participants discontinuing due to AEs |
|
| Deaths |
|
|
|
|
| ALT High |
|
| BUN High |
|
| CK High |
|
|
| QT change from baseline >30 msec; <=60 msec |
|
| QTcF change from baseline >60 msec |
|
| QTcF change from baseline >30 msec; <=60 msec |
|