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| ID | Type | Description | Link |
|---|---|---|---|
| 2008_568 |
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This study will compare graded glucose infusion (GGI) to the hyperglycemic clamp (HGC) for assessment of glucose-dependent insulin secretion (GDIS) using exenatide as a probe.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | exenatide 5mcg |
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| 2 | Active Comparator | exenatide 1.5mcg |
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| 3 | Placebo Comparator | Placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Comparator: exenatide | Drug | exenatide in two 5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 5mcg doses will be administered, followed by HCG or GGI. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose | Comparison of Glucose Dependent Insulin Secretion (GDIS) measured after HGC at steady-state to GDIS measured after GGI at the highest glucose infusion rate. Insulin Secretion Rate (ISR)/ Blood Glucose (BG) | Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose |
| Change From Baseline in C-peptide Concentration | Pre and Post glucose infusion | |
| Change From Baseline in Insulin Concentration | Pre and Post glucose infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27072496 | Result | Shankar SS, Shankar RR, Mixson LA, Miller DL, Chung C, Cilissen C, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Linearity of beta-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series. Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E865-73. doi: 10.1152/ajpendo.00527.2015. Epub 2016 Apr 12. |
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Inclusion criteria: Subjects with a Body Mass Index (BMI) of ≤26 kg/m2
Exclusion criteria: History of diabetes or family history of diabetes.
Subjects on a carbohydrate restricted diet.
An amendment added 8 subjects to go before study completion and instituted down dosing for subjects assigned to exenatide 5 μg in the HGC period to placebo
First Patient Entered: 19-Sep-2008
Last Patient, Last Visit: 05-Mar-2009
1 site
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| ID | Title | Description |
|---|---|---|
| FG000 | HGC - Exenatide 5 μg | Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg |
| FG001 | HGC - Exenatide 1.5 μg | Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 Procedure/Treatment Groups |
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| Comparator: exenatide | Drug | exenatide in two 1.5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 1.5mcg doses will be administered, followed by HCG or GGI. |
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| Comparator: Placebo | Drug | 5% osmitrol in two 60 mcL subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 60 mcL doses will be administered, followed by HCG or GGI. |
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| FG002 | HGC - Placebo | Hyperglycemic Clamp: Treatment Group Placebo |
| FG003 | Exenatide 5 ug Down Dosed to Placebo (HGC) | Hyperglycemic Clamp: Treatment Group Exenatide 5 ug down dosed to placebo |
| FG004 | GGI - Exenatide 5 μg | Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg |
| FG005 | GGI - Exenatide 1.5 μg | Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg |
| FG006 | Placebo (HGC or GGI) | Hyperglycemic Clamp or Graded Glucose Infusion: Treatment Group Placebo |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 Procedure/Treatment Groups |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Patients | All patients from all arms |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Gender | Count of Participants | Participants |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| 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 From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose | Comparison of Glucose Dependent Insulin Secretion (GDIS) measured after HGC at steady-state to GDIS measured after GGI at the highest glucose infusion rate. Insulin Secretion Rate (ISR)/ Blood Glucose (BG) | All subjects treated | Posted | Geometric Mean | Full Range | (ng/min) / (mg/dL) | Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose |
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| Primary | Change From Baseline in C-peptide Concentration | All subjects treated | Posted | Least Squares Mean | Full Range | ng/mL | Pre and Post glucose infusion |
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| Primary | Change From Baseline in Insulin Concentration | All subjects treated | Posted | Least Squares Mean | Full Range | μIU(insulin)/mL | Pre and Post glucose infusion |
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Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed.
AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
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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 | HGC - Exenatide 5 μg | Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg | 0 | 9 | 4 | 9 | ||
| EG001 | HGC - Exenatide 1.5 μg | Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg | 0 | 9 | 4 | 9 | ||
| EG002 | HGC - Placebo | Hyperglycemic Clamp: Treatment Group Placebo | 0 | 10 | 4 | 10 | ||
| EG003 | GGI - Exenatide 5 μg | Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg | 1 | 7 | 6 | 7 | ||
| EG004 | GGI - Exenatide 1.5 μg | Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg | 0 | 8 | 3 | 8 | ||
| EG005 | GGI - Placebo | Graded Glucose Infusion: Treatment Group Placebo | 0 | 11 | 2 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 12.0 | Systematic Assessment |
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| Abdominal Discomfort | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Retching | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Tooth Abscess | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Procedural Pain | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
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| Blood Phosphorus Decreased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Disturbance In Attention | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Rash Papular | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Thrombophlebitis Superficial | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D000077270 | Exenatide |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
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| <0.001 |
| Least Squares Mean |
| 0.95 |
| 90 |
| 0.66 |
| 1.24 |
| No |
| Superiority or Other |
| ANOVA | 1-sided, alpha=0.05 | <0.001 | Least Squares Mean | 2.32 | 90 | 1.57 | 3.06 | No | Superiority or Other |
| ANOVA | 1-sided, alpha = 0.05 | <0.001 | Least Squares Mean | 1.38 | 90 | 0.64 | 2.12 | No | Superiority or Other |
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