Assess the Effect of Cangrelor at the Therapeutic Dose and a Supratherapeutic Dose Level on the QT/QTc Interval in Healthy Volunteers

NCT00699504 | Completed Phase 1

• 1 other identifier: TMC CAN 08 01
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the safety of cangrelor on cardiac repolarization as measured by electrocardiogram (ECG) at therapeutic and supratherapeutic doses.

Conditions

Healthy

Keywords

ECG; QT; Effect of study drug on healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Change from baseline in placebo adjusted QTc with the individual correction method (QTcI) following cangrelor administration.

  Baseline to treatment

Secondary Outcomes (1)

• Plasma concentrations of study drug and metabolite

  Baseline to treatment

Study Arms (5)

Lead in Phase

EXPERIMENTAL

Supratherapeutic dose of cangrelor

Drug: cangrelor

A

EXPERIMENTAL

therapeutic dose cangrelor treatment

Drug: cangrelor

B

EXPERIMENTAL

supratherapeutic dose cangrelor treatment

Drug: cangrelor

C

ACTIVE COMPARATOR

active comparator treatment

Drug: moxifloxacin

D

PLACEBO COMPARATOR

placebo treatment

Drug: placebo

Interventions

cangrelor DRUG

IV bolus 60 mcg/kg; 8 mcg/kg x 3 hrs

Lead in Phase

moxifloxacin DRUG

400 mg orally. Placebo IV bolus and infusion.

C

placebo DRUG

placebo IV and oral

D

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or non pregnant female between 18 years and 45 years of age, inclusive.
• Female subjects of childbearing potential (ie, who have not undergone a hysterectomy, have not had a tubal ligation, have not been postmenopausal for at least 12 consecutive months, or whose partner has not undergone a vasectomy) must commit either to abstain continuously from heterosexual sexual contact or to use two methods of birth control, one of which must be a barrier method (eg, hormonal contraception, latex condom, diaphragm, or cervical cap), beginning at screening and throughout study participation.
• A body mass index (BMI) of 19 kg/m2 to 28 kg/m2, inclusive.
• Agrees to abstain from alcohol consumption for at least 3 days before first dosing with study drug and throughout study participation.
• Agrees to abstain from caffeine and nicotine replacement therapy during the days of study drug administration and serial ECG measurements.
• No clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory tests during screening.
• Serum magnesium and potassium levels within the normal range per the local lab at the time of screening.
• Healthy volunteer as determined by the screening assessments.
• Willing and able to comply with all trial requirements.
• Provide written informed consent before initiation of any study related procedures.

You may not qualify if:

• Known or suspected pregnancy.
• Increased bleeding risk: ischemic stroke within the last year or any previous hemorrhagic stroke, tumor, or intracranial aneurysm; recent (\<1 month) trauma or major surgery; active bleeding.
• Impaired hemostasis: known International Normalized Ratio (INR) \>1.5; past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand's disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count \<100,000/µL).
• Sustained supine systolic blood pressure \>140 mmHg or \<100 mmHg or a diastolic blood pressure \>95 mmHg or \<60 mmHg at screening or baseline. Blood pressure may be retested twice in the supine position at intervals of 5 minutes. Blood pressure is considered sustained if either the systolic or the diastolic pressure exceeds the stated limits after three assessments.
• Resting pulse rate of \<50 beats per minute (bpm) or \>100 bpm.
• Abnormality in the 12 lead ECG that, in the opinion of the investigator, increases the risk of participating in the study, such as a corrected QT interval (QTcB or QTcF) \>450 milliseconds. The following conduction abnormalities may confound QTc analysis and should be avoided: PR \>220 milliseconds, second or third degree atrioventricular (AV) block, intraventricular conduction defect (IVCD) with QRS \>120 milliseconds, complete left bundle branch block (LBBB), left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), right bundle branch block (RBBB), or Wolff Parkinson White syndrome (WPW) (WPW defined as PR \>120 milliseconds, P axis from 1 to 90, QRS complex \>120 milliseconds, delta wave present).
• Personal history of long QT syndrome, heart failure, or hypokalemia.
• Personal history of unexplained syncope.
• Immediate-family history of long QT syndrome.
• Family history of sudden death.
• Concurrent medical conditions, therapy, or medications that affect the ECG, especially prolongation of the QT/QTc interval.
• Use of prescription or over the counter (such as pseudoephedrine containing cold medicines) medication, including herbal remedies and health supplements, known to prolong the QT/QTc interval within 14 days prior to start of the study and throughout study participation.
• Current smokers or subjects who have discontinued smoking fewer than 6 months prior to study entry.
• Donation of any blood or plasma in the last month, or donation of \>400 mL of blood within the 3 months preceding study drug administration.
• Clinically significant abnormalities in clinical laboratory test results.

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (1)

Charles River Clinical Services NW

Tacoma, Washington, 98418, United States

Location

Related Publications (1)

• Green CL, Whellan DJ, Lambe L, Bellibas SE, Wijngaard P, Prats J, Krucoff MW. Electrocardiographic safety of cangrelor, a new intravenous antiplatelet agent: a randomized, double-blind, placebo- and moxifloxacin-controlled thorough QT study. J Cardiovasc Pharmacol. 2013 Nov;62(5):466-78. doi: 10.1097/FJC.0b013e3182a2630d.

  PMID: 23921301 DERIVED

MeSH Terms

Interventions

cangrelor; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2008
• First Posted: June 18, 2008
• Study Start: June 1, 2008
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: January 18, 2012

Record last verified: 2012-01

Locations

US (1)