Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01300260
First received: February 3, 2011
Last updated: October 3, 2014
Last verified: October 2014
Results First Received: October 3, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Biological: LY2189265
Drug: Placebo
Drug: Insulin
Drug: Glucose
Drug: Glucagon

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
LY2189265 First, Then Placebo

Includes healthy participants or participants with T2DM. LY2189265 (Dulaglutide): Single 1.5 milligram (mg) subcutaneous (SC) injection on Day 1 of Period 1. Placebo: Single SC injection of Placebo on Day 1 of Period 2.

On Day 3 of each period, participants received a 6-hour (hr) insulin infusion, followed by an intravenous (IV) dextrose bolus (50% dextrose bolus, 0.3 gram/kilogram [g/kg] over approximately 2 minutes [min]). Three hr later, a 2nd IV dextrose bolus 25 g of 50% dextrose or a suitably adjusted dose according to glycemic status (20 g of 50% dextrose for participants with 3-hr glucose between 5.2 and 10 millimole/liter [mmol/L] or 15 g of 50% dextrose for participants with 3-hr glucose >10 mmol/L) was administered, followed by a 20% dextrose at the set infusion rate of 600 milliliter/hr [mL/hr] for 35 min. Fifteen min after the start of the 20% dextrose infusion, an IV 1-mg glucagon bolus was administered.

There was a washout period of ≥28 days between Periods 1 & 2.

Placebo First, Then LY2189265

Includes healthy participants and participants with T2DM. Placebo: Single subcutaneous (SC) injection of Placebo on Day 1 of Period 1. LY2189265 (Dulaglutide): Single 1.5 milligram (mg) SC injection on Day 1 of Period 2.

On Day 3 of each period, participants received a 6-hour (hr) insulin infusion, followed by an intravenous (IV) dextrose bolus (50% dextrose bolus, 0.3 gram/kilogram [g/kg] over approximately 2 minutes [min]). Three hr later, a 2nd IV dextrose bolus 25 g of 50% dextrose or a suitably adjusted dose according to glycemic status (20 g of 50% dextrose for participants with 3-hr glucose between 5.2 and 10 millimole/liter [mmol/L] or 15 g of 50% dextrose for participants with 3-hr glucose >10 mmol/L) was administered, followed by a 20% dextrose at the set infusion rate of 600 milliliter/hr [mL/hr] for 35 min. Fifteen min after the start of the 20% dextrose infusion, an IV 1-mg glucagon bolus was administered.

There was a washout period of ≥28 days between Periods 1 & 2.


Participant Flow for 3 periods

Period 1:   Period 1 of Study: First Intervention
    LY2189265 First, Then Placebo     Placebo First, Then LY2189265  
STARTED     15     17  
Received at Least 1 Dose of Study Drug     15     17  
COMPLETED     14     16  
NOT COMPLETED     1     1  
Adverse Event                 0                 1  
Withdrawal by Subject                 1                 0  

Period 2:   Washout Period of at Least 28 Days
    LY2189265 First, Then Placebo     Placebo First, Then LY2189265  
STARTED     14     16  
COMPLETED     14     16  
NOT COMPLETED     0     0  

Period 3:   Period 2 of Study: Second Intervention
    LY2189265 First, Then Placebo     Placebo First, Then LY2189265  
STARTED     14     16  
COMPLETED     14     15  
NOT COMPLETED     0     1  
Adverse Event                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Healthy participants or participants with type 2 diabetes mellitus (T2DM) who received at least one dose of study drug (LY2189265 or Placebo).

Reporting Groups
  Description
Healthy Participants Includes healthy participants randomized to receive 1.5 milligram (mg) LY2189265 (Dulaglutide) first or Placebo first on Day 1 of either treatment sequence.
Participants With Type 2 Diabetes Mellitus (T2DM) Includes participants with T2DM randomized to receive 1.5 mg LY2189265 (Dulaglutide) first or Placebo first on Day 1 of either treatment sequence.
Total Total of all reporting groups

Baseline Measures
    Healthy Participants     Participants With Type 2 Diabetes Mellitus (T2DM)     Total  
Number of Participants  
[units: participants]
  10     22     32  
Age  
[units: years]
Mean ± Standard Deviation
  51.9  ± 5.0     56.3  ± 6.1     54.9  ± 6.1  
Gender  
[units: participants]
     
Female     3     7     10  
Male     7     15     22  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     0     0     0  
Not Hispanic or Latino     10     22     32  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     0     0     0  
White     10     22     32  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
Germany     10     22     32  



  Outcome Measures
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1.  Primary:   Maximum Insulin Concentration (Cmax) - First Phase Response   [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 postdose ]

2.  Primary:   Area Under the Insulin Concentration-time Curve (AUC) - First Phase Response   [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 postdose ]

3.  Primary:   Maximum Insulin Concentration (Cmax) - Second Phase Response   [ Time Frame: 10-180 minutes after dextrose bolus on Day 3 postdose ]

4.  Primary:   Insulin Area Under the Curve (AUC) - Second Phase Response   [ Time Frame: 10-180 minutes after dextrose bolus on Day 3 post dose ]

5.  Secondary:   Insulin Maximum Concentration (Cmax)   [ Time Frame: After glucagon bolus on Day 3 postdose ]

6.  Other Pre-specified:   Area Under the Insulin Concentration-time Curve (AUC)   [ Time Frame: After glucagon bolus on Day 3 postdose ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01300260     History of Changes
Other Study ID Numbers: 11371, H9X-MC-GBCI
Study First Received: February 3, 2011
Results First Received: October 3, 2014
Last Updated: October 3, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices