Reversibility of Apixaban Anticoagulation With the Four Factor Prothrombin Complex Concentrate Kcentra

NCT02270918 | Completed Phase 1

• 1 other identifier: 14P.366
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Apixaban is an anticoagulant (also known as blood thinner) approved by the Food and Drug Administration (FDA) for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. It has no reliable method of reversal. Kcentra is an FDA approved drug derived from blood that is used as an antidote to treat people with bleeding associated with taking the well-known anticoagulant warfarin. This is a Phase I, placebo-controlled, single site, open-label, crossover trial to evaluate the reversibility apixaban anticoagulation with Kcentra.

Conditions

Thrombosis

Keywords

Xa inhibitor; Prothrombin complex concentrate; anticoagulation

Outcome Measures

Primary Outcomes (1)

• thrombin generation assay (TGA)

  30 minutes

Secondary Outcomes (1)

• Anti-factor Xa activity

  30 minutes

Other Outcomes (2)

• prothrombin time (PT)

  30 minutes

• activated partial thromboplastin time (PTT)

  30 minutes

Study Arms (2)

Apixaban with Kcentra

ACTIVE COMPARATOR

Oral apixaban will be administered to steady state in healthy volunteers followed by a single infusion of prothrombin complex concentrate Kcentra at 25 units/Kg

Drug: Kcentra; Drug: Apixaban

Apixaban with placebo

PLACEBO COMPARATOR

Oral apixaban will be administered to steady state in healthy volunteers followed by a single infusion of saline

Drug: Apixaban; Drug: Placebo

Interventions

Kcentra DRUG

IV infusion

Also known as: 4 factor prothrombin complex concentrate

Apixaban with Kcentra

Apixaban DRUG

Apixaban with Kcentra; Apixaban with placebo

Placebo DRUG

Apixaban with placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible for participation in this trial, the subject must:
• Be a healthy male or female between ages 18-55 (inclusive) at the screening visit
• Have a body mass index (BMI) \>19 and \<33 (inclusive)
• If a female, subject
• Can be of childbearing potential and must demonstrate a urine β-hCG level consistent with the nongravid state at the pretrial (screening) visit and agree to use (and/or have their partner use) an acceptable method of birth control beginning at the pretrial visit throughout the trial (including washout intervals between treatment periods) and until 2 weeks after the last dose of trial drug in the last treatment period.
• Can be of non-childbearing potential which is defined as: a female who is postmenopausal without menses for at least 1 year and an Follicle stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation and/or a female who is status post hysterectomy, oophorectomy or tubal ligation
• Must be off hormonal oral or transdermal contraceptives for at least 4 weeks prior to initial dose of trial drug
• Be a nonsmoker for at least approximately 6 months
• Have serum creatinine level \< 1.5 mg/dL
• Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal
• Have platelet count within normal limits
• Be willing to refrain from the use of anticoagulants and antiplatelet medications including aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) during the entire period of study participation
• Be willing to provide written informed consent for the trial
• Be willing to comply with trial restrictions

You may not qualify if:

• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Has history of cancer (excluding treated cutaneous squamous or basal cell carcinoma of \>3 years previous)
• Has history of venous or arterial thromboembolic disease
• Has a history of clinically significant bleeding risks including prior serious head trauma
• Has had major surgery within 6 months prior to screening visit
• Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies for 2 weeks prior to trial start date until the post-trial visit
• Is unable to refrain from using any drugs or substance known to be inhibitors or inducers of cytochrome P450 (CYP) enzymes including grapefruit products for 2 weeks prior to dosing and throughout the study, until the post-trial visit
• Has a history of illicit drug abuse within six months prior to screening visit
• Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day and cannot refrain from alcohol for the duration of the trial
• Has a history of significant multiple and/or severe allergies (e.g. food, drug), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Has known anaphylactic or severe systemic reactions to any components of study drugs (including heparin induced thrombocytopenia) or contraindication to the administration of PCC or any other related blood products.
• Has moderate or severe hepatic disease or other clinically relevant bleeding risk
• Has positive history for hepatitis B surface antigen, hepatitis C or HIV
• Has first degree relatives with history of bleeding disorder or hypercoagulable disease
• Use of any drugs or products which at the discretion of the investigator would increase bleeding risk

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Bristol-Myers Squibb: collaborator
• CSL Behring: collaborator

Study Sites (1)

Thomas Jefferson University Hosptial

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Nagalla S, Thomson L, Oppong Y, Bachman B, Chervoneva I, Kraft WK. Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers. Clin Transl Sci. 2016 Jun;9(3):176-80. doi: 10.1111/cts.12398. Epub 2016 May 12.

  PMID: 27170068 RESULT

MeSH Terms

Conditions

Thrombosis; Hemophilia B

Interventions

apixaban

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Walter K Kraft, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 21, 2014
• Study Start: November 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 7, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)