Pharmacokinetics of Everolimus in Absorb BVS in Patients With Coronary Artery Lesions

NCT02229864 | Completed Results DMC

• 1 other identifier: 10-392 B
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The ABSORB III PK sub-study is a prospective, open-label, non-blinded study enrolling approximately 12 subjects in up to 5 US sites. ABSORB III PK sub-study is a part of ABSORB III RCT (NCT01751906). The objective is to determine the pharmacokinetics of everolimus delivered by the Absorb BVS in a separate and non-randomized cohort of subjects who only receive Absorb BVS with a maximum of two de novo native coronary artery lesions after implantation of the Absorb BVS. Note: The ABSORB III PK subjects will not contribute to the determination of the ABSORB III RCT primary endpoint.

Conditions

Coronary Artery Disease; Coronary Artery Stenosis; Coronary Disease; Coronary Stenosis

Keywords

Absorb™ BVS; Angioplasty; Bioabsorbable; BVS; Coronary Artery Disease; Coronary Artery Endothelial Responsiveness; Coronary artery restenosis; Coronary artery stenosis; Coronary scaffold; Coronary Stent; Drug eluting stents; Everolimus; Myocardial ischemia; Stent thrombosis; Stents

Outcome Measures

Primary Outcomes (8)

• Maximum Concentration (Cmax)

  Maximal observed blood analyte concentration. Cmax is the highest blood everolimus concentration reached during the 30 day period of the study after assessing at different time frames (10 minutes, 30 minutes, 1 hr, 2 hrs, 4 hrs, 6 hrs , 12 hrs, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 14 days, and 30 days post implantation).

  0 to 30 days

• Time of Maximum (Tmax)

  Time to reach the maximal observed blood analyte concentration during the 30 day period of the study after assessing at different time frames (10 minutes, 30 minutes, 1 hr, 2 hrs, 4 hrs, 6 hrs , 12 hrs, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 14 days, and 30 days post implantation).

  0 to 30 days

• AUC24h

  Area under the blood analyte concentration vs. time curve from time 0 up to 24 hours post placement of the last Absorb BVS. Calculated by the Lin Up Log Down trapezoidal method.

  0 to 24 hours

• AUC Last

  Area under the blood analyte concentration vs. time curve from time 0 up to the last quantifiable concentration reached during the 30 day period of the study. After assessing at different time frames (10 minutes, 30 minutes, 1 hr, 2 hrs, 4 hrs, 6 hrs , 12 hrs, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 14 days, and 30 days post implantation). Calculated by the Lin Up Log Down trapezoidal method.

  0 to 30 days

• AUC 0-infinity

  AUC 0-infinity: Area under the blood analyte concentration vs. time curve from time zero and extrapolated to infinite time, reached during the 30 day period of the study. After assessing at different time frames (10 minutes, 30 minutes, 1 hr, 2 hrs, 4 hrs, 6 hrs , 12 hrs, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 14 days, and 30 days post implantation). calculated as: AUC0-∞ = AUClast + (Clast/λz) The percentage of AUC0-∞ obtained by extrapolation (%AUC0-∞ex) is calculated as: %AUC0-∞ex = (AUC0-∞ - AUClast)/ AUC0-∞ \* 100

  0 to 30 days

• Terminal Elimination Rate Constant (λz)

  The apparent terminal elimination rate constant during the 30 day period of the study. After assessing at different time frames (10 minutes, 30 minutes, 1 hr, 2 hrs, 4 hrs, 6 hrs , 12 hrs, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 14 days, and 30 days post implantation). Determined by linear regression of terminal points of the ln-linear analyte concentration-time curve.

  0 to 30 days

• Terminal Elimination Half-life (t1/2term)

  The apparent terminal elimination half-life, reached during the 30 day period of the study. After assessing at different time frames (10 minutes, 30 minutes, 1 hr, 2 hrs, 4 hrs, 6 hrs , 12 hrs, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 14 days, and 30 days post implantation). calculated as: t1/2term = 0.693/λz.

  0 to 30 days

• Drug Clearance (CL)

  The systemic drug clearance, reached during the 30 day period of the study. After assessing at different time frames (10 minutes, 30 minutes, 1 hr, 2 hrs, 4 hrs, 6 hrs , 12 hrs, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 14 days, and 30 days post implantation). Calculated as: CL = Dose/AUC0 - ∞ .

  0 to 30 days

Secondary Outcomes (10)

• Number of Participants With Target Lesion Failure (TLF)

  0 to 1853 Days

• Number of Participants With All Death

  0 to 1853 Days

• Number of Participants With All Myocardial Infarction (MI)

  0 to 1853 Days

• Number of Participants With All Target Lesion Revascularization (TLR)

  0 to 1853 Days

• Number of Participants With All Target Vessel Revascularization (TVR)

  0 to 1853 Days

Study Arms (1)

Coronary artery stenting: Absorb BVS

EXPERIMENTAL

Subjects receiving Absorb Bioresorbable Vascular Scaffold (BVS)

Device: Coronary artery stenting: Absorb BVS

Interventions

Coronary artery stenting: Absorb BVS DEVICE

* Scaffold diameters: 2.5, 3.0 and 3.5 mm * Scaffold lengths: 8, 12, 18, and 28 mm

Coronary artery stenting: Absorb BVS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age.
• Subject or a legally authorized representative must provide written Informed Consent prior to any study related procedure, per site requirements.
• Evidence of myocardial. In the absence of noninvasive ischemia, FFR must be done and indicative of ischemia.
• An acceptable candidate for coronary artery bypass graft (CABG) surgery.
• Female subject of childbearing potential who does not plan pregnancy for up to 1 year following the index procedure.
• Female subject is not breast-feeding at the time of the screening visit and will not be breast-feeding for up to 1 year following the index procedure.
• Subject agrees to not participate in any other investigational or invasive clinical study for a period of 1 year following the index procedure.
• One or two de novo target lesions:
• If two target lesions are present, they must be present in different epicardial vessels and both must satisfy the angiographic eligibility criteria.
• The definition of epicardial vessels means the left anterior descending (LAD), left coronary artery (LCX), and right coronary artery (RCA) and their branches. Thus, the patient must not have lesions requiring treatment in e.g. both the LAD and a diagonal branch.
• Target lesion(s) must be located in a native coronary artery with a visually estimated or quantitatively assessed % diameter stenosis (DS) of ≥ 50% and \< 100% with a thrombolysis in myocardial infarction (TIMI) flow of ≥ 1 and one of the following: stenosis ≥ 70%, an abnormal functional test (e.g., fractional flow reserve (FFR), stress test), unstable angina or post-infarct angina.
• Lesion(s) must be located in a native coronary artery with reference vessel diameter (RVD) by visual estimation of ≥ 2.50 mm and ≤ 3.75 mm.
• Lesion(s) must be located in a native coronary artery with length by visual estimation of ≤ 24 mm.

You may not qualify if:

• Any surgery requiring general anesthesia or discontinuation of aspirin and/or an Adenosine diphosphate receptor (ADP) antagonist is planned within 12 months after the procedure.
• Subject has known hypersensitivity or contraindication to device material and its degradants (everolimus, poly (L-lactide), poly (DL-lactide), lactide, lactic acid) and cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoro polymers that cannot be adequately pre-medicated. Subject has a known contrast sensitivity that cannot be adequately pre-medicated.
• Subject has known allergic reaction, hypersensitivity or contraindication to aspirin; or to clopidogrel and prasugrel and ticagrelor; or to heparin and bivalirudin, and therefore cannot be adequately treated with study medications.
• Subject had an acute myocardial infarction (AMI: STEMI or NSTEMI) within 72 hours of the index procedure and both creatine kinase (CK) and creatine kinase myocardial-band isoenzyme (CK-MB) have not returned to within normal limits at the time of index procedure; or subject with stable angina or silent ischemia has CK-MB that is greater than normal limits at the time of the index procedure.
• Subject is currently experiencing clinical symptoms consistent with new onset AMI (STEMI or NSTEMI), such as nitrate-unresponsive prolonged chest pain with ischemic ECG changes.
• Subject has a cardiac arrhythmia as identified at the time of screening for which at least one of the following criteria is met:
• Subject requires coumadin or any other agent for chronic oral anticoagulation
• Subject is likely to become hemodynamically unstable due to their arrhythmia
• Subject has poor survival prognosis due to their arrhythmia
• Subject has a left ventricular ejection fraction (LVEF) \< 30%
• Subject has undergone prior percutaneous coronary intervention (PCI) within the target vessel(s) during the last 12 months.
• Subject requires future staged PCI either in target or non-target vessels or subject requires future peripheral interventions \< 30 days after the index procedure.
• Subject has received any solid organ transplants or is on a waiting list for any solid organ transplants.
• At the time of screening, the subject has a malignancy that is not in remission.
• Subject is receiving immunosuppressant therapy or has known immunosuppressive or severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.). Note: corticosteroids are not included as immunosuppressant therapy.

Sponsors & Collaborators

• Abbott Medical Devices: lead

Study Sites (2)

Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

Cardiac & Vascular Research Center of Northern Michigan

Petoskey, Michigan, 49770, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease; Coronary Stenosis; Coronary Disease; Coronary Restenosis; Myocardial Ischemia

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Latania Chura
• Organization: Abbott Vascular

latania.chura@abbott.com

503-935-3002

Study Officials

• David G. Rizik, MD

  Scottsdale Healthcare, Scottsdale, AZ

  PRINCIPAL INVESTIGATOR

• Louis A. Cannon, MD

  Cardiac and Vascular Research Center of Northern Michigan Petoskey, MI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2014
• First Posted: September 3, 2014
• Study Start: May 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2019
• Last Updated: March 12, 2021
• Results First Posted: December 14, 2016

Record last verified: 2021-03

Locations

US (2)