Effect of Clarithromycin on the Pharmacokinetics of Apixaban in Healthy Participants

This study is to evaluate the effects of multiple-dose clarithromycin on the single-dose pharmacokinetics (PK) of apixaban with parameters like Cmax, AUC(INF), and AUC(0-T).

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Apixaban; Drug: Clarithromycin

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Ppd Development, Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Informed Consent
2. Target population: Healthy subjects as determined by medical history, surgical history, physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory tests including coagulation parameters.
3. Subjects with body mass index of 18 to 30 kg/m2, inclusive
4. Women must not be breast feeding, have a negative serum or urine pregnancy test and must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatments apixaban and clarithromycin plus 5 half-lives of study treatments apixaban and clarithromycin plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion.
5. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatments apixaban and clarithromycin plus 5 half-lives of the study treatment plus 30 days for a total of 33 days post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.

Exclusion Criteria:

1. History of any significant medical illness, drug allergy including allergy to apixaban, FXa inhibitors (and/or their excipients), clarithromycin, macrolides, and/or related compounds. History of substance abuse and use of nicotine containing products and/or alcohol abuse.
2. History of coagulopathy, prolonged or unexplained clinically significant bleeding, or frequent unexplained bruising or thrombus formation, including hypermenorrhea, intra-cranial hemorrhage, family history of bleeding disorders in first degree relatives, and/or any adverse reaction to anticoagulants or antiplatelet agents that resulted in excessive bleeding.
3. History of recurrent neurological or gastrointestinal disorders, including insomnia, chronic headaches, dizziness, gastroesophageal reflux disease, cholecystectomy, gastric ulcers and/or Gilbert's syndrome.
4. History of antibiotic induced secondary infections, including candidiasis.
5. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory tests beyond what is consistent with the target population.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apixaban and Clarithromycin	Drug: Apixaban; Multiple-dose clarithromycin and single-dose Apixaban; Drug: Clarithromycin; Multiple-dose clarithromycin and single-dose Apixaban

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax)	Days 1-11
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))	Days 1-11
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))	Days 1-11

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and death	Screening- until 30 days after discontinuation of dosing or subject's participation in the study if the last

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Garonzik S, Byon W, Myers E, Li X, Marchisin D, Murthy B. The Effects of Clarithromycin on the Pharmacokinetics of Apixaban in Healthy Volunteers: A Single-Sequence Crossover Study. Am J Cardiovasc Drugs. 2019 Dec;19(6):561-567. doi: 10.1007/s40256-019-00348-2.

Helpful Links

• BMS Clinical Trial Education Resource
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: September 19, 2016
• First Submitted That Met QC Criteria: September 21, 2016
• First Posted (Estimate): September 23, 2016

Study Record Updates

• Last Update Posted (Estimate): November 21, 2016
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban; Clarithromycin
• Other Study ID Numbers: CV185-547