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 12, 2011
Last verified: October 2011

February 3, 2011
October 12, 2011
February 2011
August 2011   (final data collection date for primary outcome measure)
  • Maximum insulin concentration (Cmax)-first phase response [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 post dose ] [ Designated as safety issue: No ]
  • Area under the insulin concentration-time curve (AUC)- first phase response [ Time Frame: 0-10 minutes after dextrose bolus on Day 3 post dose ] [ Designated as safety issue: No ]
  • Maximum Insulin concentration (Cmax) - second phase response [ Time Frame: 10 -180 minutes after dextrose bolus on Day 3 post dose ] [ Designated as safety issue: No ]
  • Insulin Area Under the Curve (AUC)- second phase response [ Time Frame: 10-180 minutes after dextrose bolus on Day 3 post dose ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01300260 on ClinicalTrials.gov Archive Site
Insulin maximum concentration (Cmax) [ Time Frame: After glucagon bolus on Day 3 post dose ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Diabetes Mellitus, Type 2
  • Biological: LY2189265
    administered subcutaneously
    Other Name: Dulaglutide
  • Drug: Placebo
    Administered subcutaneously
  • Experimental: LY2189265 then Placebo

    Single 1.5 mg subcutaneous injection of LY2189265 on day 1 in period one then single subcutaneous injection of placebo on day 1 in period 2.

    There is a washout period of at least 28 days between periods 1 and 2.

    Interventions:
    • Biological: LY2189265
    • Drug: Placebo
  • Experimental: Placebo then LY2189265

    Single subcutaneous injection of placebo on day 1 in period one then single 1.5 mg subcutaneous injection of LY2189265 on day 1 in period 2.

    There is a washout period of at least 28 days between periods 1 and 2.

    Interventions:
    • Biological: LY2189265
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
August 2011
August 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

All Subjects

  • Women must be surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation) or postmenopausal as defined by age >45 years without use of oral contraceptive agents for greater than 1 year and have either:

    • spontaneous amenorrhea greater than 12 months, or
    • spontaneous amenorrhea 6 to 12 months with documented follicle stimulating hormone (FSH) >25 mIU/mL
  • Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
  • Have given written informed consent approved by Lilly and the ethical review board governing the site
  • Have serum creatinine <150 micromol/L [<1.3 mg/dl] in women, <170 micromol/L [<1.5 mg/dl] in men
  • Have normal haemoglobin result, as determined by the investigator

Healthy Subjects

  • Overtly healthy men and women as determined by medical history, normal lab results and physical examination.
  • Body mass index (BMI) between 19 and 25 kg/m2, inclusive.
  • Normal blood pressure and heart rate as determined by the investigator
  • Have a normal response to an OGTT (glucose <7.8 mmol/L [<140 mg/dl] at 2 hours after 75g oral glucose load)

Subjects with type 2 diabetes

  • Subjects will have a BMI between 22.0 and 40.0 kg/m2
  • Have T2DM controlled with diet and exercise alone or metformin for at least 4 weeks prior to admission
  • Have a haemoglobin 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.
  • Subjects 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.

Exclusion Criteria:

All Subjects

  • 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 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 subject's physician(s)
  • History or presence of cardiovascular, respiratory, renal, endocrine (except T2DM), haematological, or neurological disorders capable of significantly altering the absorption, or 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 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 described in section 5.4 (1 unit = 12 oz or 360 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 haematology, clinical chemistry, or urinary result(s) as determined by the investigator
  • Evidence of significant active uncontrolled endocrine or autoimmune abnormalities (for example thyroid disease, pernicious anaemia) as judged by the screening physician

Healthy Subjects

  • Intended use of over-the-counter or prescription medication 7 and 14 days, respectively, prior to dosing.

Subjects with T2DM

  • Clinically significant peripheral vascular occlusive disease (PVOD).
  • Known severe exudative diabetic retinopathy
  • Known significant autonomic neuropathy as evidenced by urinary retention, diabetic diarrhoea, or gastroparesis
  • Have experienced a ketoacidotic episode (pH less than 7.3) requiring hospitalisation 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
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01300260
11371, H9X-MC-GBCI
No
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
Eli Lilly and Company
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP