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

Phase 1

Completed

• Conditions: Elevated Lipoprotein(a); Cardiovascular Diseases
• Interventions: Drug: ISIS 681257; Drug: Warfarin

• Registration Number: NCT03426033
• Lead Sponsor: Akcea Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-15
• Study First Submitted: 2018-01-03
• Study First Submitted QC: 2018-02-06
• Study First Posted: 2018-02-08
• Primary Completion: 2018-02-25
• Study Completion: 2018-02-25
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-03
• Last Update Posted: 2018-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Warfarin in combination with ISIS 681257	ISIS 681257	ISIS 681257 administered and pharmacokinetic assessments are taken. Then ISIS 681257 is administered with warfarin and additional pharmacokinetic information is obtained.
Single dose of warfarin	Warfarin	Single dose of warfarin administered to obtain pharmacokinetic information.
Warfarin in combination with ISIS 681257	Warfarin	ISIS 681257 administered and pharmacokinetic assessments are taken. Then ISIS 681257 is administered with warfarin and additional pharmacokinetic information is obtained.

Primary Outcome Measures

Name	Time	Method
The plasma concentrations of warfarin and ISIS 681257 will be measured at each individual time point.	Each day for days 1-10 and 15-45	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.

Secondary Outcome Measures

Name	Time	Method
The safety of ISIS 681257 by the incidence of treatment-emergent adverse events.	45 days	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.
Prothrombin Time will be measured by testing blood samples at each individual time point.	Each day for days 1-7 and 15-21	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.
International normalized ratio will be measured at each individual time point by comparing prothrombin time to the normal mean prothrombin time.	Each day for days 1-7 and 15-21	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.
Activated partial thromboplastin time will be measured by testing blood samples at each individual time point.	Each day for days 1-7 and 15-21	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.
The plasma concentrations of warfarin and ISIS 681257 will be measured at each individual time point.	Each day for days 1-10 and 15-45	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.

Trial Locations

Locations (1)

Clinical Site; 🇨🇦 Mount Royal, Quebec, Canada