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Trial · Interventional

CompletedPhase 1Results postedRegistry data

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

NCTNCT01432938 (opens ClinicalTrials.gov in a new tab)Other id11549Other idH9X-MC-GBCS

Overview

Status
Completed
Phase
Phase 1
Enrollment
28 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
Sept 2011
Primary completion
Dec 2011
Completion
Dec 2011
First posted
13 Sept 2011 (estimated)
Last update posted
7 Oct 2014 (estimated)
Conditions
Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20112012
  1. Ph 1

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

    NCT01432938

    Sept 2011 to Dec 2011

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • dulaglutideBiological
  • WarfarinDrug

Arms2

  • Experimental

    Warfarin first, then Dulaglutide + Warfarin

    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).

  • Experimental

    Dulaglutide + Warfarin first, then Warfarin

    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).

Primary outcomes3

Outcomes the sponsor listed as primary.

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

    Time frame · 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)

    Registry description

    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.

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

    Time frame · 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)

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

    Time frame · 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)
  1. Pharmacodynamics: Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin

    Time frame · 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)

    Registry description

    AUCINR was assessed from venous blood samples collected to determine the response variable INR at predose and at pre-determined intervals after the administration of warfarin.

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

    Time frame · 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)

    Registry description

    Observed INRmax was assessed from venous blood samples collected to determine the response variable INR at predose and at pre-determined intervals after the administration of warfarin.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeGeometric mean· 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: Area Under the Concentration Versus Time Curve (AUC) of R-warfarin and S-warfarin

GroupValue (nanograms times hours per milliliter)Spread
Warfarin Alone1920024
Dulaglutide + Warfarin1890022
Primary outcomeGeometric mean· 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

GroupValue (nanograms per milliliter (ng/mL))Spread
Warfarin Alone53019
Dulaglutide + Warfarin41423
Primary outcomeMedian· 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

GroupValue (hours)
Warfarin Alone2.00
Dulaglutide + Warfarin4.00
Secondary and other outcome results(2)
Secondary outcomeGeometric mean· 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: Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin

GroupValue (ratio)Spread
Warfarin Alone1575
Dulaglutide + Warfarin1615
Secondary outcomeGeometric mean· 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

GroupValue (ratio)Spread
Warfarin Alone1.2413
Dulaglutide + Warfarin1.2715

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Warfarin AloneA single, 10-milligram (mg) dose administered orally on Day 1 of Treatment 1. Timeframe: Treatment 1–0 / 283 / 28
Dulaglutide AloneA single, 1.5-mg dose administered subcutaneously on Day 1 of Treatment 2. Timeframe: Day 1 to Day 3 before dosing of warfarin in Treatment 2–0 / 265 / 26
Dulaglutide + WarfarinA single, 1.5-mg dose of dulaglutide administered subcutaneously on Day 1 of Treatment 2, followed by a single, 10-mg dose of warfarin administered orally on Day 3 of Treatment 2 Timeframe: After dosing of warfarin on Day 3 of Treatment 2–0 / 254 / 25

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2017

11 results

No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide.

de la Peña et al. 2017Clinical pharmacokineticscited by 22

PMID 28357715DOI 10.1007/s40262-017-0531-7PUB-28357715

Full text at the publisher11 results

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 65 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 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 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 * 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 the first dose of warfarin or dulaglutide or prescription medication (with the exception of vitamin/mineral supplements and/or hormone replacement therapy \[HRT\]) within 14 days prior to dosing. Aspirin and other nonsteroidal anti-inflammatory drugs should not be taken from 2 weeks prior to the first dosing occasion * show intended use of any drug or dietary supplement that may affect warfarin or coagulation within 14 days prior to the first dose of warfarin or dulaglutide or during the conduct of the study * use or intended use of a drug that inhibits or induces cytochrome P450 (CYP)1A2, CYP2C9, CYP2C19, or CYP3A4 within 14 days prior to the first dose of warfarin or dulaglutide or during the conduct of the study * have donated blood of more than 500 milliliters (mL) within the month prior to screening * have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to stop alcohol consumption from 48 hours prior to admission (Day -1 of the first treatment period) until discharge (1 unit = 12 ounces \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits) * are smokers * have an international normalized ratio/prothrombin time (INR/PT) or activated partial thromboplastin time (aPTT) above the normal reference range at screening * are females who menstruate * have consumed grapefruit, cranberries, or grapefruit- or cranberry-containing products within 7 days prior to the first dose of warfarin or dulaglutide * in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study * have any medical conditions, medical history or are taking any medication which are contraindicated within the warfarin Product Information Leaflet

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