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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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In this study, the researchers hope to learn about SGLT2 inhibition on EGP (endogenous glucose production) and plasma glucose concentration in diabetic subjects. Researchers will examine diabetes and the role of increased plasma glucagon, decline in plasma insulin, and fall in plasma glucose concentration.
This study will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose concentration compared to each agent alone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Byetta / Bydureon | Active Comparator | Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc |
|
| Dapagliflozin | Active Comparator | 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg |
|
| Byetta/Bydureon plus Dapagliflozin | Active Comparator | Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS Dapagliflozin: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg |
|
| Placebo | Placebo Comparator | Placebo group (4 weeks and 12 weeks) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin | Drug | 10mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment | After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg + exenatide 5 ug [ACUTE STUDY]. | ACUTE [after a single dose of each study drug or placebo] |
| Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug. | After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug. Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period. Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination. Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective "acute" studies. | 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) Concentration | The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eugenio Cersosimo, MD,PhD | The University of Texas Health Science Center at San Antonio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas Health Science Center | San Antonio | Texas | 78229 | United States |
Type 2 diabetes with significant clinical complications were excluded
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| ID | Title | Description |
|---|---|---|
| FG000 | Byetta / Bydureon | Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) |
| FG001 | Dapagliflozin | 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg |
| FG002 | Byetta/Bydureon Plus Dapagliflozin | Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS Dapagliflozin: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) |
| FG003 | Placebo | Placebo group (4 weeks and 12 weeks) Placebo: Placebo for Dapagliflozin |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Acute Portion of Study |
| |||||||||||||
| 16 Week Drug Administration Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Byetta / Bydureon | Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) |
| BG001 | 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 | Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment | After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg + exenatide 5 ug [ACUTE STUDY]. | Type 2 diabetes | Posted | Mean | Standard Error | mg/kg.min | ACUTE [after a single dose of each study drug or placebo] |
|
Baseline to 6 months
Patient reporting and physical exam by principal investigator/nurse coordinator
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Byetta / Bydureon | Exenatide: 4 weeks of exenatide 5 mcg twice daily followed by Bydureon 2mg sc weekly Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Genital Mycosis | Reproductive system and breast disorders | Systematic Assessment | Nausea and Vomiting |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor | University of Texas Health San Antonio | 12103587200 | cersosimo@uthscsa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 8, 2020 | Apr 13, 2023 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C529054 | dapagliflozin |
| D000077270 | Exenatide |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
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| Exenatide | Drug | Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) |
|
|
| Placebo | Drug | Placebo for Dapagliflozin |
|
| 16 weeks |
| Change in Plasma Glucagon Concentration | Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin. | Baseline to 16 weeks |
| Change in Plasma Insulin Concentration | Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s). Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin. | Baseline to 16 weeks |
| COMPLETED |
|
| NOT COMPLETED |
|
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg
Dapagliflozin: 10mg
| BG002 | Byetta/Bydureon Plus Dapagliflozin | Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS Dapagliflozin: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) |
| BG003 | Placebo | Placebo group (4 weeks and 12 weeks) Placebo: Placebo for Dapagliflozin |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Dapagliflozin | After acute single dose exposure of Dapagliflozin, Farxiga, 10mg |
| OG002 | Exenatide Plus Dapagliflozin | After acute exposure to both dapagliflozin, farxiga 10 mg orally and a single subcutaneous injection of Exenatide |
| OG003 | Placebo | After a single dose of placebo |
|
|
| Secondary | Change in Fasting Plasma Glucose (FPG) Concentration | The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin. | type 2 diabetes | Posted | Mean | Standard Error | mg/dl | 16 weeks |
|
|
|
| Secondary | Change in Plasma Glucagon Concentration | Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin. | type 2 diabetes | Posted | Mean | Standard Error | pg/ml | Baseline to 16 weeks |
|
|
|
| Secondary | Change in Plasma Insulin Concentration | Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s). Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin. | Type 2 diabetes | Posted | Mean | Standard Error | microUnits/ml | Baseline to 16 weeks |
|
|
|
| Primary | Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug. | After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug. Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period. Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination. Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective "acute" studies. | Type 2 diabetes | Posted | Mean | Standard Error | mg/kg.min | 16 weeks |
|
|
|
| 0 |
| 25 |
| 0 |
| 25 |
| 6 |
| 25 |
| EG001 | Dapagliflozin | 16 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg | 0 | 25 | 0 | 25 | 4 | 25 |
| EG002 | Byetta/Bydureon Plus Dapagliflozin | Exenatide: 4 weeks of exenatide followed by 12 weeks of Bydureon 2mg sc once weekly PLUS Dapagliflozin: 16 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) | 0 | 25 | 0 | 25 | 7 | 25 |
| EG003 | Placebo | 16 weeks of placebo administration | 0 | 15 | 0 | 15 | 0 | 15 |
|
| Nausea and Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D014118 |
| Toxins, Biological |
| D001685 | Biological Factors |