A Single Dose Study of LY2189265 in Subjects With Varying Degrees of Hepatic (Liver) Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01253304
First received: December 1, 2010
Last updated: November 30, 2011
Last verified: November 2011
  Purpose

The primary purpose of this study is to help answer the following research questions, and not to provide treatment for any condition:

  • To evaluate how much of the study drug (LY2189265) is in the blood of subjects with varying degrees of liver impairment compared to those with normal liver function.
  • To assess the safety of LY2189265 and any side effects that might be associated with it.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: LY2189265
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Dose Pharmacokinetic Study of LY2189265 in Subjects With Varying Degrees of Hepatic Impairment

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics, maximum observed concentration (Cmax) [ Time Frame: Days 1, 2, 3, 4, 5, 8 and 15 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, time of maximum concentration (Tmax) [ Time Frame: Days 1, 2, 3, 4, 5, 8 and 15 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, area under the concentration versus time curve from time zero to the last quantifiable concentration (AUC0-tlast) [ Time Frame: Days 1, 2, 3, 4, 5, 8 and 15 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, AUC from time zero to infinity (AUC0-∞) [ Time Frame: Days 1, 2, 3, 4, 5, 8 and 15 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, apparent terminal elimination half-life (t1/2) [ Time Frame: Days 1, 2, 3, 4, 5, 8 and 15 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, apparent total plasma clearance (CL/F) [ Time Frame: Days 1, 2, 3, 4, 5, 8 and 15 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, apparent volume of distribution (Vz/F) [ Time Frame: Days 1, 2, 3, 4, 5, 8 and 15 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: November 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: normal hepatic function
Single subcutaneous 1.5 mg dose on day 1
Drug: LY2189265
Administered subcutaneous
Other Name: Dulaglutide
Experimental: mild hepatic impairment
Single subcutaneous 1.5 mg dose on day 1
Drug: LY2189265
Administered subcutaneous
Other Name: Dulaglutide
Experimental: moderate hepatic impairment
Single subcutaneous 1.5 mg dose on day 1
Drug: LY2189265
Administered subcutaneous
Other Name: Dulaglutide
Experimental: severe hepatic impairment
Single subcutaneous 1.5 mg dose on day 1
Drug: LY2189265
Administered subcutaneous
Other Name: Dulaglutide

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All Subjects (Including Patients with Type 2 Diabetes Mellitus):

  • Male subjects - Agree to use a reliable method of birth control (for example, barrier methods) during the study and for at least 3 months following dosing of study drug
  • Female subjects:

    • Women must be of non-child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal ligation) or menopause
    • Women with an intact uterus are deemed postmenopausal if they are over 45 years old and have had cessation of menses for at least 1 year or,have had 6 to 12 months of spontaneous amenorrhea with follicle stimulating hormone (FSH) >40 IU/mL; and have not taken hormone replacement therapy or oral contraceptives within 1 year of study start and are otherwise healthy
    • Women who have had cessation of menses for at least 2 years are permitted to take hormone replacement therapy
  • Have a body mass index (BMI) between 19.0 and 40.0 kg/m2, inclusive, at screening
  • Have venous access sufficient to allow blood sampling 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 governing the site

Control Subjects:

  • Overtly healthy subjects with normal hepatic function
  • Patients with Type 2 Diabetes Mellitus (T2DM) with normal hepatic function
  • Have normal sitting blood pressure and pulse rate as determined by the investigator, or with changes compatible with their age and disease status in case of patients with T2DM
  • Have clinical laboratory test results within normal reference range for the investigator site, or results with minor deviations not considered to be clinically significant by the investigator or with changes compatible with their age and disease status in case of T2DM

Hepatic Impaired Subjects:

  • Have stable hepatic impairment (e.g. post-alcoholic, chronic hepatitis, biliary cirrhosis, cryptogenic, etc.) classified as Child-Pugh Class A, B, or C (mild, moderate, and severe impairment) who are considered by the investigator as acceptable for participation in the study. The hepatic impaired subjects population may include patients with T2DM.
  • Have sitting blood pressure and pulse rate compatible with their disease state [including T2DM, if applicable] as determined by the investigator Patients with Type 2 Diabetes Mellitus (All Study Groups)
  • Have T2DM controlled with diet and exercise alone or stable on a single oral agent antihyperglycemic medication (metformin, sulfonylureas, repaglinide, nateglinide, acarbose [or other disaccharidase inhibitors] or thiazolidinediones) for at least 3 weeks (3 months for thiazolidinediones) prior to admission
  • Have a HbA1C value at screening (or within 4 weeks prior to screening) of 6.5% to 9.0%
  • Have 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
  • Have acceptable blood pressure and pulse rate (sitting), as determined by the investigator

Exclusion Criteria:

All subjects (Including Patients with Type 2 Diabetes Mellitus)

  • Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving use of an investigational drug or device other than the study drug, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Have known allergies to LY2189265 or related compounds
  • Have previously completed or withdrawn from this study or any other study investigating LY2189265
  • Have a current, functioning, organ transplant
  • Show evidence of significant active uncontrolled endocrine or autoimmune abnormalities (e.g. thyroid disease, pernicious anemia) as judged by the screening physician
  • Have shown febrile illness within 3 days prior to screening
  • 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
  • Regularly use known drugs of abuse and/or show positive findings on urinary drug screening that are not otherwise explained by permitted concomitant medications
  • Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies
  • Are women with a positive pregnancy test or women who are lactating
  • Have donated blood of more than 500 mL within the last month prior to screening
  • Have an average weekly alcohol intake that exceeds 21 units per week (men) and 14 units per week (women), (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)
  • Are unwilling to stop alcohol consumption for the duration of the study (from screening until the follow-up visit)
  • Are subjects who smoke more than 10 cigarettes per day, are unwilling to refrain from smoking on the day of LY2189265 administration or are unable to abide by clinical research unit (CRU) restrictions on other inpatient days
  • Have a history or presence of pancreatitis [history of chronic pancreatitis or idiopathic acute pancreatitis] or gastrointestinal disorder, for example relevant esophageal reflux or gall bladder disease, or any gastrointestinal disease which impacts gastric emptying (e.g. gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon like peptide (GLP) analogs. Subjects with mild hypertension and dyslipidaemia, and subjects who had cholecystolithiasis (removal of gall stones) and/or cholecystectomy (removal of gall bladder) in the past, with no further sequelae, may be included in the study at the discretion of the screening physician.
  • Are subjects deemed to be unsuitable by the investigator for any reason.

Control subjects:

  • Have a history or presence of cardiovascular (myocardial infarction, cerebrovascular accident, venous thromboembolism), respiratory, renal, endocrine (with exception of subjects with T2DM), hematological, or neurological disorders, cancer, hepatic (including Gilbert's disease), or dermatological disorder or disease capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
  • Show evidence of significant active neuropsychiatric disease.
  • Have creatinine clearance less than 80 mL/min (as calculated by the Cockcroft-Gault equation
  • Show evidence of hepatitis B and/or positive hepatitis B surface antigen
  • Show evidence of hepatitis C and/or positive hepatitis C antibody
  • Intend to use:

    • over-the-counter medication (including herbal remedies/health supplements) within 7 days prior to dosing
    • prescription medication within 14 days prior to dosing Subjects with Mild, Moderate, and Severe Hepatic Impairment
  • Show evidence of any significant active disease other than that responsible for or associated with hepatic impairment. Subjects with hypertension and hyperlipidemia may be permitted at the investigator's discretion.
  • Show, in the opinion of the investigator, evidence of significant neuropsychiatric disease other than Grade 1 hepatic encephalopathy
  • Show evidence of spontaneous bacterial peritonitis within 6 months of dosing.
  • Show evidence of severe hyponatremia (Na <120 mmol/L)
  • Show presence of hepatocellular carcinoma
  • Have a portal shunt
  • Show evidence of severe ascites
  • Have hemoglobin <9.0 g/dL
  • Have platelet count <40x10^9 cells/L
  • Have total serum bilirubin >15 mg/dL
  • Use medication known to interfere with hepatic metabolism (that is, barbiturates, phenothiazines) or known to alter other major organs or systems

Mild, Hepatic Impaired Subjects (Child-Pugh A)

  • Show evidence of active renal disease with creatinine clearance <70 mL/min calculated by the Cockcroft-Gault equation.

Moderate and Severe Hepatic Impaired Subjects (Child-Pugh B and C)

•Show evidence of hepatorenal syndrome as shown by creatinine clearance <50 mL/min calculated by the Cockcroft-Gault equation.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01253304

Locations
Germany
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.
Munich, Germany, 81241
Hungary
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.
Budapest, Hungary, 1032
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01253304     History of Changes
Other Study ID Numbers: 13765, H9X-EW-GBDO
Study First Received: December 1, 2010
Last Updated: November 30, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 17, 2014