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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT00699504
First received: June 13, 2008
Last updated: January 13, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
Healthy
Drug: cangrelor
Drug: moxifloxacin
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: A Double Blind, Placebo Controlled, Positive Controlled, Randomized, Crossover Study to Assess the Effect of Cangrelor at the Therapeutic Dose and a Supratherapeutic Dose Level on the QT/QTc Interval in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Change from baseline in placebo adjusted QTc with the individual correction method (QTcI) following cangrelor administration. [ Time Frame: Baseline to treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma concentrations of study drug and metabolite [ Time Frame: Baseline to treatment ] [ Designated as safety issue: Yes ]

Enrollment: 67
Study Start Date: June 2008
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lead in Phase
Supratherapeutic dose of cangrelor
Drug: cangrelor
IV bolus 60 mcg/kg; 8 mcg/kg x 3 hrs
Experimental: A
therapeutic dose cangrelor treatment
Drug: cangrelor
30 mcg/kg bolus; 4 mcg/kg/min x 3 hrs. Oral placebo capsule
Experimental: B
supratherapeutic dose cangrelor treatment
Drug: cangrelor
60 mcg/kg bolus; 8 mcg/kg/min x 3 hrs. Oral placebo capsule
Active Comparator: C
active comparator treatment
Drug: moxifloxacin
400 mg orally. Placebo IV bolus and infusion.
Placebo Comparator: D
placebo treatment
Drug: placebo
placebo IV and oral

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or non pregnant female between 18 years and 45 years of age, inclusive.
  2. 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.
  3. A body mass index (BMI) of 19 kg/m2 to 28 kg/m2, inclusive.
  4. Agrees to abstain from alcohol consumption for at least 3 days before first dosing with study drug and throughout study participation.
  5. Agrees to abstain from caffeine and nicotine replacement therapy during the days of study drug administration and serial ECG measurements.
  6. No clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory tests during screening.
  7. Serum magnesium and potassium levels within the normal range per the local lab at the time of screening.
  8. Healthy volunteer as determined by the screening assessments.
  9. Willing and able to comply with all trial requirements.
  10. Provide written informed consent before initiation of any study related procedures.

Exclusion Criteria:

  1. Known or suspected pregnancy.
  2. 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.
  3. 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).
  4. 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.
  5. Resting pulse rate of <50 beats per minute (bpm) or >100 bpm.
  6. 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).
  7. Personal history of long QT syndrome, heart failure, or hypokalemia.
  8. Personal history of unexplained syncope.
  9. Immediate-family history of long QT syndrome.
  10. Family history of sudden death.
  11. Concurrent medical conditions, therapy, or medications that affect the ECG, especially prolongation of the QT/QTc interval.
  12. 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.
  13. Intention to use prescription (other than thyroid hormone replacement if the dose and regimen of such replacement therapy has been stable for at least 4 weeks prior to screening and is expected to remain stable during study participation or hormonal contraception) or over the counter medication, including herbal remedies and health supplements, within 14 days before the initial dose of study drug and throughout study participation. If this situation arises, inclusion of an otherwise suitable volunteer may be at the discretion of the investigator in discussion with the Sponsor.
  14. Current smokers or subjects who have discontinued smoking fewer than 6 months prior to study entry.
  15. 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.
  16. Clinically significant abnormalities in clinical laboratory test results.
  17. Positive virology screen for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  18. Positive urine test for drugs of abuse or alcohol.
  19. Clinically significant disease or condition affecting a major organ system, including, but not limited to, gastrointestinal, renal, hepatic, bronchopulmonary, neurological, metabolic or cardiovascular disease.
  20. Allergy, hypersensitivity, or contraindication to quinolone antibiotics, cangrelor, or any of their excipients.
  21. History of multiple adverse drug allergies of any origin.
  22. Deemed by the investigator, for any reason, to be inappropriate for this study, including subjects who are unable to communicate or to cooperate with the investigator.
  23. Treatment with other investigational agents or devices within the 30 days preceding randomization, planned use of other investigational drugs or devices during study participation, or previous enrollment in this trial.
  24. Inability to give informed consent or high likelihood of being unable to complete the necessary confinement.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00699504

Locations
United States, Washington
Charles River Clinical Services NW
Tacoma, Washington, United States, 98418
Sponsors and Collaborators
The Medicines Company
  More Information

No publications provided by The Medicines Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT00699504     History of Changes
Other Study ID Numbers: TMC CAN 08 01
Study First Received: June 13, 2008
Last Updated: January 13, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by The Medicines Company:
ECG
QT
Effect of study drug on healthy volunteers

Additional relevant MeSH terms:
Cangrelor
Moxifloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014