Clinical trial NCT01301092: A Study to Compare the Concentrations of LY2189265 After Different Methods of Administration to Healthy Volunteers.
Official title: A Study to Evaluate the Safety, Tolerability, and Absolute Bioavailability of Subcutaneous LY2189265
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type II
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-02-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: LY2189265 is an investigational drug being developed for the treatment of type 2 diabetes mellitus. This study will compare the concentrations of LY2189265 using different methods of administration: subcutaneous (or SC- an injection just under the skin), intravenous (or IV - into a vein in the arm) and intramuscular (IM - into the muscle of the left thigh). The purpose of this study is to look at how much of the drug gets into the blood stream and how long it takes the body to get rid of it when given by the methods above. The study is divided into three parts, Part A, B and C. Volunteers will only be able to participate in one part. All Participants in Part A will receive a single IV dose of up to 0.1 milligram (mg). Participants in Part B will be given drug twice by IV and an SC injection (1.5 mg). Part B of the study will occur after Part A because the dose of IV drug will depend on the results of Part A. Part B of the study may not occur if the volunteers in Part A do not tolerate the drug. Participants in Part C will also be given drug twice by an SC injection and an IM injection, both doses will be 0.75 mg.


Eligibility criteria: Inclusion Criteria:

* Are overtly healthy males or females, as determined by medical history and physical examination.
* Male subjects with female partners of child-bearing potential, or partners who are pregnant or breastfeeding, agree to use a reliable method of contraception from the time of the first dose until 3 months after the last dose of investigational product, as determined by the investigator. The method may be one of the following: condom with spermicidal agent, male subject sterilization, true abstinence (which is in line with the subject's usual lifestyle choice; withdrawal or calendar methods are not considered acceptable).
* Female subjects not of child-bearing potential (that is, are postmenopausal or permanently sterilized \[for example, tubal occlusion, hysterectomy, bilateral salpingectomy\]). Such subjects will not be required to use contraception but must test negative for pregnancy at the time of enrollment. Postmenopausal is defined as at least 1 year post cessation of menses (without an alternative medical cause) with follicle stimulating hormone (FSH) greater than or equal to 40 milli-international units per milliliter (mIU/mL).
* Female subjects who have undergone sterilization by tubal ligation: agree to use a condom in conjunction with spermicidal gel, foam, cream, film or suppository from the time of screening until 3 months after the last dose of investigational product. Such subjects must also test negative for pregnancy at the time of enrollment.
* Have a body mass index (BMI) of between 23.0 and 35.0 kilogram/square meter (kg/m²), inclusive.
* Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.
* Have normal sitting blood pressure and pulse rate as determined by the investigator, or with changes compatible with their age.
* Have venous access sufficient to allow for blood sampling and/or IV administration of investigational product as per the protocol.
* 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 (ERB) governing the site.

Exclusion Criteria:

* Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
* Are women of child bearing potential
* Have known allergies to Glucagon-like peptide-1 (GLP-1)-related compounds including LY2189265.
* Are persons who have previously completed or withdrawn from this study or any other study investigating LY2189265.
* Have an abnormality in the 12-lead Electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study.
* Have a history or presence of gastrointestinal disorder (including pancreatitis \[history of chronic pancreatitis or idiopathic acute pancreatitis\] or gall bladder disease), or gastrointestinal disease that impacts gastric emptying (GE) (for example, gastric bypass surgery, pyloric stenosis) or could be aggravated by GLP analogs (for example, esophageal reflux). Subjects having had cholecystolithiasis (removal of gall stones), cholecystectomy (removal of gall bladder) and/or appendectomy in the past with no further sequelae may be included in the study at the discretion of the screening physician.
* Have a history or presence of significant active neuropsychiatric disease
* Regularly use known drugs of abuse and/or show positive findings on urinary drug screening.
* Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies.
* Show evidence of hepatitis C and/or positive hepatitis C antibody.
* Show evidence of hepatitis B and/or positive hepatitis B surface antigen.
* Are women with a positive pregnancy test or women who are lactating.
* Use or intend to use over-the-counter medication other than paracetamol within 7 days prior to dosing or prescription medication (with the exception of vitamin/mineral supplements and/or hormone replacement therapy and/or thyroid replacement therapy) within 14 days prior to dosing.
* Have donated blood of more than 500 mL within the last month.
* Are subjects who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), (1 unit = 12 ounce \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits), or are unwilling to stop alcohol consumption from at least 24 hours prior to screening and each dose, and while resident at the clinical research unit (CRU).
* Are subjects who smoke more than 10 cigarettes per day, are unwilling to refrain from smoking on the day of LY2189265 administration and while resident.
* Are subjects who, in the opinion of the investigator, are in any way unsuitable to participate in the study.

Primary outcomes:
measure: Dose Normalized Area Under the Concentration Time Curve (AUC) of LY2189265: Subcutaneous (SC) to Intravenous (IV)
timeFrame: Predose up to 336 hours postdose
measure: Maximum Concentration (Cmax) of LY2189265: Subcutaneous (SC) to Intravenous (IV)
timeFrame: Predose up to 336 hours postdose
Secondary outcomes:
measure: Area Under the Concentration Time Curve (AUC) of LY2189265: Intramuscular (IM) to Subcutaneous (SC)
timeFrame: Predose up to 336 hours postdose
measure: )Maximum Concentration (Cmax) of LY2189265: Intramuscular (IM) to Subcutaneous (SC)
timeFrame: Predose up to 336 hours postdose
Other outcomes:
Locations:
city: Evansville
country: United States
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.
state: Indiana
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: