Clinical trial NCT01300260: Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose
Official title: The Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose Infusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-02-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the effect of LY2189265 to increase insulin levels in response to glucose intake.


Eligibility criteria: Inclusion Criteria:

All Participants

* 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 milli international units/milliliter (mIU/mL) and serum estradiol \<73 picomoles/liter (pmol/L) (20 picograms/milliliter \[pg/mL\])
* 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 micromoles/liter (µmol/L) (\<1.3 milligrams/deciliter \[mg/dl\] in women, \<170 µmol/L \[\<1.5 mg/dL\] in men)
* Have normal hemoglobin result, as determined by the investigator

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

Primary outcomes:
measure: Maximum Insulin Concentration (Cmax) - First Phase Response
timeFrame: 0-10 minutes after dextrose bolus on Day 3 postdose
measure: Area Under the Insulin Concentration-time Curve (AUC) - First Phase Response
timeFrame: 0-10 minutes after dextrose bolus on Day 3 postdose
measure: Maximum Insulin Concentration (Cmax) - Second Phase Response
timeFrame: 10-180 minutes after dextrose bolus on Day 3 postdose
measure: Insulin Area Under the Curve (AUC) - Second Phase Response
timeFrame: 10-180 minutes after dextrose bolus on Day 3 post dose
Secondary outcomes:
measure: Insulin Maximum Concentration (Cmax)
timeFrame: After glucagon bolus on Day 3 postdose
Other outcomes:
measure: Area Under the Insulin Concentration-time Curve (AUC)
timeFrame: After glucagon bolus on Day 3 postdose
Locations:
city: Neuss
country: Germany
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: