A Study of the Effect of Dulaglutide on How Body Handles Digoxin in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01436201
First received: September 15, 2011
Last updated: April 2, 2012
Last verified: April 2012
  Purpose

The purpose of this study is to study how the body processes digoxin and the effect of dulaglutide on how digoxin is processed by the body. Information about any side effects that may occur will also be collected.

This study is for research purposes only and is not intended to treat any medical condition. This research study requires that a blood sample be obtained and stored for future research involving genetic analysis.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Digoxin
Biological: Dulaglutide
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: Effect of Dulaglutide (LY2189265) on the Pharmacokinetics of Digoxin in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics: area under the concentration versus time curve (AUC) of Digoxin [ Time Frame: Predose (digoxin) and up to 24 hours post dose on Days 7, 10 and 17 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: maximum observed drug concentration (Cmax) of Digoxin [ Time Frame: Predose (digoxin) and up to 24 hours postdose on Days 7, 10 and 17 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: time of maximum observed drug concentration (tmax) of Digoxin [ Time Frame: Predose (Digoxin) and up to 24 hours postdose on Days 7, 10 and 17 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: September 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Digoxin + Dulaglutide
Two 0.5 mg doses (2 x 0.25 mg tablets per dose) of Digoxin will be administered orally 12 hours apart on Day 1 (1 mg total dose, on Day 1). Digoxin 0.25 mg will then be administered orally once daily on Days 2 to 17. Dulaglutide 1.5 mg will be co-administered as a single subcutaneous injection on two separate occasions on Days 8 and 15.
Drug: Digoxin
Administered orally
Biological: Dulaglutide
Administered as subcutaneous injection
Other Name: LY2189265

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 (i.e. are postmenopausal or permanently sterilized [e.g. tubal occlusion, hysterectomy, bilateral salpingectomy]). Such subjects will not be required to use contraception but must test negative for pregnancy at the time of enrolment Postmenopausal is defined as at least 1 year post cessation of menses (without an alternative medical cause) or at least 1 year of spontaneous amenorrhea, with follicle stimulating hormone (FSH) ≥40 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 enrolment
  • have a body mass index (BMI) of 18.5 to 32.0 kg/m2, inclusive, at screening
  • 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 (potassium, magnesium, and calcium values must be within the normal range)
  • have normal renal function defined as an estimated creatinine clearance (CrCl) of ≥80 mL/min
  • have venous access sufficient to allow for blood sampling
  • are reliable and willing to make themselves available for the duration of the study and are willing to follow study restrictions
  • have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site

Exclusion Criteria:

  • are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product, 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 glucagon like peptide -1 (GLP-1)-related compounds including dulaglutide or to digoxin, related compounds or any components of either formulation
  • are persons who have previously completed or withdrawn from this study or any other study investigating dulaglutide in the 3 months prior to screening or have received glucagon-like peptides or incretin mimetics in the 3 months prior to screening have an abnormality in the 12-lead electrocardiogram (ECG) (e.g. first, second, or third degree atrioventricular (AV) block, prolonged QTc interval, sinus tachycardia, sinus bradycardia, atrial fibrillation, or sinus node disease) that, in the opinion of the investigator, increases the risks associated with participating in the study
  • have a history of significant dysrhythmias or AV block.
  • have an abnormal blood pressure (after at least 5 minutes sitting) that, in the opinion of the investigator, increases the risks associated with participating in the study
  • have a history or presence of cardiac, respiratory, hepatic, renal, endocrine (e.g. hypothyroidism), hematological, or neurological disorders 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
  • 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 (GE) (e.g. gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon like peptide-1 (GLP-1) analogs. Subjects with dyslipidemia, and subjects who had cholecystolithiasis (removal of gall stones) and/or cholecystectomy (removal of gall bladder) in the past, with no further sequelae.
  • show evidence of significant active neuropsychiatric disease
  • have family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC
  • regularly use known drugs of abuse and/or show positive findings on urinary drug screening
  • show evidence of human immunodeficiency virus (HIV) infection 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
  • have used or intend to use over-the-counter medication other than acetaminophen within 7 days prior to dosing or prescription medication (with the exception of vitamin/mineral supplements) within 14 days prior to dosing, or have used St John's Wort within 14 days prior to dosing
  • have donated blood of more than 500 mL within the month prior to screening and 14 units per week (females), or are unwilling to stop alcohol consumption from screening through follow-up (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 smokers
  • have a history of cancer with the past 20 years, with the exception of basal cell or squamous cell skin cancer, or treated cervical carcinoma in situ
  • intend to consume grapefruit within 7 days prior to dosing
  • are subjects who, in the opinion of the investigator, are in any way unsuitable to participate in the study
  • have any medical conditions, medical history or are taking any medication which are contraindicated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01436201

Locations
United States, Florida
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.
Daytona Beach, Florida, United States, 32117
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: NCT01436201     History of Changes
Other Study ID Numbers: 11550, H9X-MC-GBCR
Study First Received: September 15, 2011
Last Updated: April 2, 2012
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
Digoxin
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014