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CompletedNCT03426033Updated Apr 5, 2018

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

A Phase 1 interventional study of ISIS 681257 and Warfarin in Elevated Lipoprotein(a) and Cardiovascular Diseases, sponsored by Akcea Therapeutics. Completed at 1 site in Canada. Open to participants aged 16 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-04-05.

Sponsored by Akcea Therapeutics · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
18
Allocation
Non-randomized
Ages
16 Years to 60 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Elevated Lipoprotein(a)
  • Cardiovascular Diseases
03

Who can participate

Ages eligible
16 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
18 participants (actual)

Study arms

  • Experimental
    Single dose of warfarin

    Single dose of warfarin administered to obtain pharmacokinetic information.

    Drug: Warfarin

  • 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 · Drug: Warfarin

Interventions

  • DrugISIS 681257

    Xmg dose administered as a subcutaneous injection

  • DrugWarfarin

    25mg tablet administered orally

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Each day for days 1-10 and 15-45

Secondary outcomes

  1. 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.

    Time frame: 45 days

  2. 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.

    Time frame: Each day for days 1-7 and 15-21

  3. 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.

    Time frame: Each day for days 1-7 and 15-21

  4. 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.

    Time frame: Each day for days 1-7 and 15-21

  5. 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.

    Time frame: Each day for days 1-10 and 15-45

06

Study locations

1 site
  • Clinical Site
    Mount Royal, Quebec H3P 3H5, Canada
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03426033
Lead sponsor
Akcea Therapeutics
Responsible party
Sponsor
First posted
Feb 8, 2018
Start date
Dec 15, 2017
Primary completion
Feb 25, 2018
Completion
Feb 25, 2018
Last update
Apr 5, 2018

Oversight

FDA-regulated drug
No
FDA-regulated device
No
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