February 3, 2011
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February 21, 2011
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October 3, 2014
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October 7, 2014
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October 7, 2014
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February 2011
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August 2011 (Final data collection date for primary outcome measure)
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- Maximum Insulin Concentration (Cmax) - First Phase Response [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 postdose ]
On Day 1 of each treatment period, all participants (healthy or with type 2 diabetes mellitus [T2DM]) received a single subcutaneous dose of either LY2189265 or placebo. On Day 3 of each treatment period, participants underwent a 6-hour insulin infusion, followed by an intravenous (IV) dextrose 50% bolus to stimulate insulin secretion. Three hours later, participants were administered a second dextrose bolus, followed by an infusion of 20% dextrose and, 15 minutes after the start of the 20% dextrose infusion, a 1-mg glucagon bolus was administered. Maximum plasma insulin concentration from 0 to 10 minutes (INSCmax[0-10]) following the first dextrose bolus (the first phase response) was corrected for baseline, where baseline was the mean of the insulin concentrations obtained between -30 and 0 minutes relative to the first dextrose bolus.
- Area Under the Insulin Concentration-time Curve (AUC) - First Phase Response [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 postdose ]
On Day 1 of each treatment period, all participants (healthy or with type 2 diabetes mellitus [T2DM]) received a single subcutaneous dose of either LY2189265 or placebo. On Day 3 of each treatment period, participants underwent a 6-hour insulin infusion, followed by an intravenous (IV) dextrose 50% bolus to stimulate insulin secretion. Three hours later, participants were administered a second dextrose bolus, followed by an infusion of 20% dextrose and, 15 minutes after the start of the 20% dextrose infusion, a 1-mg glucagon bolus was administered. Area under the plasma insulin concentration time curve from 0 to 10 minutes (INSAUC[0-10]) following the first dextrose bolus (the first phase response) was corrected for baseline, where baseline was the mean of the insulin concentrations obtained between -30 and 0 minutes relative to the first dextrose bolus.
- Maximum Insulin Concentration (Cmax) - Second Phase Response [ Time Frame: 10-180 minutes after dextrose bolus on Day 3 postdose ]
On Day 1 of each treatment period, all participants (healthy or with type 2 diabetes mellitus [T2DM]) received a single subcutaneous dose of either LY2189265 or placebo. On Day 3 of each treatment period, participants underwent a 6-hour insulin infusion, followed by an intravenous (IV) dextrose 50% bolus to stimulate insulin secretion. Three hours later, participants were administered a second dextrose bolus, followed by an infusion of 20% dextrose and, 15 minutes after the start of the 20% dextrose infusion, a 1-mg glucagon bolus was administered. Maximum plasma insulin concentration from 10 to 180 minutes (INSCmax[10-180]) following the first dextrose bolus (the second phase response) was corrected for baseline, where baseline was the mean of the insulin concentrations obtained between -30 and 0 minutes relative to the first dextrose bolus.
- Insulin Area Under the Curve (AUC) - Second Phase Response [ Time Frame: 10-180 minutes after dextrose bolus on Day 3 post dose ]
On Day 1 of each treatment period, all participants (healthy or with type 2 diabetes mellitus [T2DM]) received a single subcutaneous dose of either LY2189265 or placebo. On Day 3 of each treatment period, participants underwent a 6-hour insulin infusion, followed by an intravenous (IV) dextrose 50% bolus to stimulate insulin secretion. Three hours later, participants were administered a second dextrose bolus, followed by an infusion of 20% dextrose and, 15 minutes after the start of the 20% dextrose infusion, a 1-mg glucagon bolus was administered. Area under the plasma insulin concentration time curve from 10 to 180 minutes (INSAUC[10-180]) following the first dextrose bolus (the second phase response) was corrected for baseline, where baseline was the mean of the insulin concentrations obtained between -30 and 0 minutes relative to the first dextrose bolus.
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- Maximum insulin concentration (Cmax)-first phase response [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 post dose ]
- Area Under the Insulin Concentration-time Curve (AUC) - First Phase Response [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 post dose ]
- Maximum Insulin Concentration (Cmax) - Second Phase Response [ Time Frame: 10 -180 minutes after dextrose bolus on Day 3 post dose ]
- Insulin Area Under the Curve (AUC) - Second Phase Response [ Time Frame: 10-180 minutes after dextrose bolus on Day 3 post dose ]
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Complete list of historical versions of study NCT01300260 on ClinicalTrials.gov Archive Site
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Insulin Maximum Concentration (Cmax) [ Time Frame: After glucagon bolus on Day 3 postdose ] On Day 1 of each treatment period, all participants (healthy or with type 2 diabetes mellitus [T2DM]) received a single subcutaneous dose of either LY2189265 or placebo. Maximum plasma insulin concentration from -2 to 20 minutes following the glucagon bolus (INSCmaxG) is presented.
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Insulin Maximum Concentration (Cmax) [ Time Frame: After glucagon bolus on Day 3 post dose ]
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Area Under the Insulin Concentration-time Curve (AUC) [ Time Frame: After glucagon bolus on Day 3 postdose ] On Day 1 of each treatment period, all participants (healthy or with type 2 diabetes mellitus [T2DM]) received a single subcutaneous dose of either LY2189265 or placebo. Area under the plasma insulin concentration-time curve from -2 to 20 minutes following the glucagon bolus (INSAUCG) is presented.
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Not Provided
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Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose |
The Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose Infusion |
The purpose of this study is to measure the effect of LY2189265 to increase insulin levels in response to glucose intake. |
Not Provided |
Interventional |
Phase 1 |
Allocation: Randomized Intervention Model: Crossover Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment |
Diabetes Mellitus, Type 2 |
- Biological: LY2189265
Administered subcutaneously
Other Name: Dulaglutide
- Drug: Placebo
Administered subcutaneously
- Drug: Insulin
Administered intravenously
Other Name: Lispro
- Drug: Glucose
Administered intravenously
Other Name: Dextrose
- Drug: Glucagon
Administered intravenously
Other Name: Glucagon hydrochloride
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- Experimental: LY2189265 then Placebo
LY2189265 (Dulaglutide) then Placebo: A single 1.5 milligram (mg) subcutaneous (SC) injection of LY2189265 on Day 1 in Period 1, followed by a single SC injection of Placebo on Day 1 in Period 2.
On Day 3 of each period, participants underwent a 6-hour insulin infusion, followed by an intravenous (IV) dextrose bolus (0.3 gram/kilogram [g/kg] over approximately 2 minutes). Three hours later, participants were administered a second IV dextrose bolus of 25 g of 50% dextrose or a suitably adjusted dose according to glycemic status (20 g of 50% dextrose for participants with 3-hour glucose between 5.2 and 10 millimole/liter [mmol/L] or 15 g of 50% dextrose for participants with 3-hour glucose >10 mmol/L), followed by a 20% dextrose at the set infusion rate of 600 milliliter/hour [mL/h] for 35 minutes. Fifteen minutes after the start of the 20% dextrose infusion, an IV 1-mg glucagon bolus was administered.
There was a washout period of at least 28 days between Periods 1 and 2.
Interventions:
- Biological: LY2189265
- Drug: Placebo
- Drug: Insulin
- Drug: Glucose
- Drug: Glucagon
- Experimental: Placebo then LY2189265
Placebo then LY2189265 (Dulaglutide): A single subcutaneous injection of Placebo on Day 1 in Period 1, followed by a single 1.5 milligrams (mg) subcutaneous injection of LY2189265 on Day 1 in Period 2.
On Day 3 of each period, participants underwent a 6-hour insulin infusion, followed by an intravenous (IV) dextrose bolus (0.3 gram/kilogram [g/kg] over approximately 2 minutes). Three hours later, participants were administered a second IV dextrose bolus of 25 g of 50% dextrose or a suitably adjusted dose according to glycemic status (20 g of 50% dextrose for participants with 3-hour glucose between 5.2 and 10 millimole/liter [mmol/L] or 15 g of 50% dextrose for participants with 3-hour glucose >10 mmol/L), followed by a 20% dextrose at the set infusion rate of 600 milliliter/hour [mL/h] for 35 minutes. Fifteen minutes after the start of the 20% dextrose infusion, an IV 1-mg glucagon bolus was administered.
There was a washout period of at least 28 days between Periods 1 and 2.
Interventions:
- Biological: LY2189265
- Drug: Placebo
- Drug: Insulin
- Drug: Glucose
- Drug: Glucagon
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Not Provided |
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Completed |
32 |
35 |
August 2011 |
August 2011 (Final data collection date for primary outcome measure) |
Inclusion Criteria:
All Participants
Healthy Participants
- Overtly healthy men and women as determined by medical history, normal lab results and physical examination.
- Body mass index (BMI) between 19 and 25 kilograms/meter squared (kg/m^2), inclusive.
- Normal blood pressure and heart rate as determined by the investigator
- Have a normal response to an oral glucose tolerance test (OGTT) (glucose <7.8 millimoles/liter [mmol/L] [<140 mg/dL] at 2 hours after 75 grams (g) oral glucose load)
Participants with type 2 diabetes mellitus (T2DM)
- Participants will have a BMI between 22.0 and 40.0 kg/m^2
- Have T2DM controlled with diet and exercise alone or metformin for at least 4 weeks prior to admission
- Have a hemoglobin A1c (HbA1c) value at screening (or within 4 weeks prior to screening) of 6.0% to 9.5%
- Diagnosed with T2DM within the past 10 years
- Clinical laboratory test results within normal range or deemed clinically insignificant by the Investigator. Abnormalities of serum glucose, serum lipids, urinary glucose, and urinary protein consistent with T2DM are acceptable.
- Participants who are taking stable-dose prescription medications (for example, antihypertensive agents, aspirin, lipid-lowering agents) for treatment of concurrent medical conditions are permitted to participate providing the medication is not associated with development of torsade de pointes. However, use of beta-blockers and thiazide diuretics are not permitted during this study.
Exclusion Criteria:
All Participants
- Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication
- Known allergies to Glucagon-Like Peptide 1 (GLP-1) related compounds
- Have previously completed or withdrawn from this study or any other study in the last year investigating glucagon-like peptides or incretin mimetics including exenatide (Byetta®)
- Regular use of known drugs of abuse and/or positive findings on urinary drug screening, other than findings consistent with medication prescribed by the participant's physician(s)
- History or presence of cardiovascular, respiratory, renal, endocrine (except T2DM), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data
- Have a history or presence of gastrointestinal disorder
- Poorly controlled hypertension (systolic greater than 160 millimeters of mercury [mmHg], diastolic greater than 95 mmHg) and/or evidence of labile blood pressure including symptomatic postural hypotension. Use of beta-blockers or thiazide diuretics is not permitted during the study
- Have a clinically significant history of cardiac disease or presence of active cardiac disease within 1 year of the screening period
- Evidence of hepatitis C and/or positive hepatitis C antibody
- Evidence of hepatitis B and/or positive hepatitis B surface antigen
- Evidence of human immunodeficiency virus (HIV) and/or positive for HIV antibodies
- Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or are unwilling to follow alcohol restrictions (1 unit = 12 ounces [oz] or 360 milliliters[mL] of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
- Smoke more than 10 cigarettes or equivalent in nicotine use or nicotine substitutes per day
- Regular use of systemic corticosteroids by oral, intravenous, or intramuscular route, or potent, inhaled, or intranasal steroids known to have a high rate of systemic absorption
- Have a history or presence of significant active neuropsychiatric disease
- Blood donation of more than 500 mL in the last 3 months or any blood donation within the last month
- Any other condition, which in the opinion of the investigator would preclude participation in the study
- An abnormality in the 12-lead electrocardiogram (ECG) that in the opinion of the investigator increases the risk of participating in the study.
- Any clinically significant abnormal hematology, clinical chemistry, or urinary result(s) as determined by the investigator
- Evidence of significant active uncontrolled endocrine or autoimmune abnormalities (for example thyroid disease, or pernicious anemia) as judged by the screening physician
Healthy Participants
- Intended use of over-the-counter or prescription medication 7 and 14 days, respectively, prior to dosing.
Participants with T2DM
- Clinically significant peripheral vascular occlusive disease (PVOD).
- Known severe exudative diabetic retinopathy
- Known significant autonomic neuropathy as evidenced by urinary retention, diabetic diarrhea, or gastroparesis
- Have experienced a ketoacidotic episode (pH less than 7.3) requiring hospitalization in the last 6 months
- Outpatient use of insulin for control of diabetes within the past 2 years
- Use of antidiabetic agents other than metformin in the 4 weeks prior to study entry or use of thiazolidinediones within 12 weeks of study entry
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Sexes Eligible for Study: |
All |
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18 Years to 65 Years (Adult) |
Yes |
Contact information is only displayed when the study is recruiting subjects |
Germany |
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NCT01300260 |
11371 H9X-MC-GBCI ( Other Identifier: Eli Lilly and Company ) |
No |
Not Provided |
Not Provided |
Eli Lilly and Company |
Eli Lilly and Company |
Not Provided |
Study Director: |
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) |
Eli Lilly and Company |
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Eli Lilly and Company |
October 2014 |