A Study of the Effect of Dulaglutide on the Action of Warfarin in Healthy Participants

NCT01432938 | Completed Phase 1 Results

• 2 other identifiers: 11549H9X-MC-GBCS
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Warfarin is a commonly used drug to prevent the blood from clotting. The purpose of this study is to determine if dulaglutide (LY2189265) affects how warfarin works. The study involves two different treatments (Treatment 1: warfarin; Treatment 2: dulaglutide + warfarin) separated by a minimum washout period of 24 days. In Treatment 1, the participant will receive 10 milligrams (mg) of warfarin on Day 1. In Treatment 2, the participant will receive a 1.5-mg dose of dulaglutide (LY2189265) as an injection on Day 1 and then a 10 mg dose of warfarin on Day 3. Participants will be randomly assigned into different treatment sequences. Participants in Treatment Sequence A will receive Treatment 1 then Treatment 2. Participants in Treatment Sequence B will receive Treatment 2 then Treatment 1.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of R-warfarin and S-warfarin

  Area under the concentration versus time curve (AUC) from zero to infinity was determined from plasma concentrations of the S- and R- enantiomers of warfarin.

  Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)

• Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of R-warfarin and S-warfarin

  Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)

• Pharmacokinetics: Time to Maximum Concentration (Tmax) of R-warfarin and S-warfarin

  Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)

Secondary Outcomes (2)

• Pharmacodynamics: Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin

  Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)

• Pharmacodynamics: Maximum Observed International Normalized Ratio (INRmax) of Warfarin

  Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)

Study Arms (2)

Warfarin first, then Dulaglutide + Warfarin

EXPERIMENTAL

A single, 10-milligram (mg) dose of warfarin administered orally on Day 1 (Treatment 1). There was a washout period of at least 24 days between treatment periods. Then a single, 1.5-mg dose of dulaglutide administered subcutaneously on Day 1, followed by a single, 10-mg dose of warfarin administered orally on Day 3 (Treatment 2).

Biological: dulaglutide; Drug: Warfarin

Dulaglutide + Warfarin first, then Warfarin

EXPERIMENTAL

A single, 1.5-mg subcutaneous dose of dulaglutide on Day 1, followed by a single, 10-mg oral dose of warfarin on Day 3 (Treatment 2). There was a washout period of at least 24 days between treatment periods. Then a single, 10-mg oral dose of warfarin on Day 1 (Treatment 1).

Biological: dulaglutide; Drug: Warfarin

Interventions

dulaglutide BIOLOGICAL

Administered subcutaneously

Also known as: LY2189265

Dulaglutide + Warfarin first, then Warfarin; Warfarin first, then Dulaglutide + Warfarin

Warfarin DRUG

Administered orally

Dulaglutide + Warfarin first, then Warfarin; Warfarin first, then Dulaglutide + Warfarin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male participants 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 participant sterilization
• true abstinence (which is in line with the participant's usual lifestyle choice; withdrawal or calendar methods are not considered acceptable)
• female participants not of child-bearing potential and are postmenopausal or have undergone a documented hysterectomy (total or partial). Such participants 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) with follicle stimulating hormone (FSH) ≥40 milli-international units per milliliter (mIU/mL)
• have a body mass index (BMI) of 18.5 to 32.0 kilograms per meter squared (kg/m\^2), 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
• 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

You may not qualify if:

• 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 warfarin, 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
• history or presence of significant bleeding disorders that is, hematemesis, melena, severe or recurrent epistaxis, hemoptysis, hematuria, or intracranial hemorrhage
• have a personal history, family history, or current evidence of a bleeding disorder, coagulopathy, or clinically significant history of bleeding complications after surgical procedures, tooth extractions, nose or gingival bleeding, spontaneous bleeding (including bleeding into joint spaces)
• have a personal or family history of polycystic kidney disease or protein C or S deficiency
• have a history of major head trauma (with loss of consciousness) within the past year or minor head trauma (without loss of consciousness) within the last 3 months prior to screening
• have a history of or plan to undergo major surgery in the last 3 months prior to screening
• show positive for a fecal occult blood test at 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
• 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 cardiovascular, respiratory, hepatic, renal, endocrine, 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) (such as, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by GLP-1 analogs. Participants with mild dyslipidemia, and participants 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
• Show evidence of significant active neuropsychiatric disease
• have family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

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.

Dallas, Texas, 75247, United States

Location

Related Publications (1)

• de la Pena A, Cui X, Geiser J, Loghin C. No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide. Clin Pharmacokinet. 2017 Nov;56(11):1415-1427. doi: 10.1007/s40262-017-0531-7.

  PMID: 28357715 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dulaglutide; Warfarin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2011
• First Posted: September 13, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 7, 2014
• Results First Posted: October 7, 2014

Record last verified: 2014-10

Locations

US (1)