Drug-drug Interaction Study to Evaluate the Effect of ISIS 681257 on Warfarin

Phase 1, Drug-Drug Interaction Study To Evaluate The Effect Of Multiple Doses Of ISIS 681257 40 mg Subcutaneous Injections On The Pharmacokinetics And Pharmacodynamics Of Warfarin In Healthy Subjects

This is a single center, open label, single sequence, two-treatment, two-period drug-drug interaction study to evaluate the effect of multiple doses of ISIS 681257 on the pharmacokinetics of a single dose of warfarin.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Elevated Lipoprotein(a)
• Intervention / Treatment: Drug: ISIS 681257; Drug: Warfarin

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Mount Royal, Quebec, Canada, H3P 3H5
      • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Motivated and available for duration of study and willing to adhere to protocol
• Males who are unable to procreate or agree to contraception throughout study
• Females who are postmenopausal or surgically sterile
• BMI between 18.5 and 30 kg/m2
• Weighing greater than or equal to 50kg
• Normal lab results
• No known diseases or significant findings on physical exam

Exclusion Criteria:

• Females of childbearing potential
• Reactions/infection at injection site
• Hypersensitivity to any drugs or similar drugs to those used in the study
• Conditions or disease that may interfere with study drug
• Any significant diseases
• Known history or familial history of bleeding disorders
• Drug dependency or abuse
• Illness within 28 days
• Previous exposure to other investigational drug within 28 days
• Blood donations within 28 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose of warfarin; Single dose of warfarin administered to obtain pharmacokinetic information.	Drug: Warfarin; 25mg tablet administered orally
Experimental: Warfarin in combination with ISIS 681257; ISIS 681257 administered and pharmacokinetic assessments are taken. Then ISIS 681257 is administered with warfarin and additional pharmacokinetic information is obtained.	Drug: ISIS 681257; Xmg dose administered as a subcutaneous injection; Drug: Warfarin; 25mg tablet administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The plasma concentrations of warfarin and ISIS 681257 will be measured at each individual time point.	To evaluate the effect of multiple doses of ISIS 681257 40 mg subcutaneous injections on the pharmacokinetics of a single oral dose of warfarin in healthy adult subjects.	Each day for days 1-10 and 15-45

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety of ISIS 681257 by the incidence of treatment-emergent adverse events.	To evaluate the safety and tolerability of multiple doses of ISIS 681257 40 mg subcutaneous injections when coadministered with a single oral dose of warfarin in healthy adult subjects.	45 days
Prothrombin Time will be measured by testing blood samples at each individual time point.	To evaluate the effect of multiple doses of ISIS 681257 40 mg subcutaneous injections on the pharmacodynamics (anticoagulant activity) of a single oral dose of warfarin in healthy adult subjects.	Each day for days 1-7 and 15-21
International normalized ratio will be measured at each individual time point by comparing prothrombin time to the normal mean prothrombin time.	To evaluate the effect of multiple doses of ISIS 681257 40 mg subcutaneous injections on the pharmacodynamics (anticoagulant activity) of a single oral dose of warfarin in healthy adult subjects.	Each day for days 1-7 and 15-21
Activated partial thromboplastin time will be measured by testing blood samples at each individual time point.	To evaluate the effect of multiple doses of ISIS 681257 40 mg subcutaneous injections on the pharmacodynamics (anticoagulant activity) of a single oral dose of warfarin in healthy adult subjects.	Each day for days 1-7 and 15-21
The plasma concentrations of warfarin and ISIS 681257 will be measured at each individual time point.	To evaluate the effect of a single dose of warfarin on the pharmacokinetics of a single subcutaneous 40 mg injection of ISIS 681257 in healthy adult subjects.	Each day for days 1-10 and 15-45

Collaborators and Investigators

• Sponsor: Akcea Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): February 25, 2018
• Study Completion (Actual): February 25, 2018

Study Registration Dates

• First Submitted: January 3, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (Actual): February 8, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: April 3, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Anticoagulants; Warfarin
• Other Study ID Numbers: ISIS 681257-CS10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No