Assess the Effect of Cangrelor at the Therapeutic Dose and a Supratherapeutic Dose Level on the QT/QTc Interval in Healthy Volunteers
Status: | Completed |
---|---|
Conditions: | Healthy Studies |
Therapuetic Areas: | Other |
Healthy: | No |
Age Range: | 18 - 45 |
Updated: | 10/14/2017 |
Start Date: | June 2008 |
End Date: | November 2008 |
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
To assess the safety of cangrelor on cardiac repolarization as measured by electrocardiogram
(ECG) at therapeutic and supratherapeutic doses.
(ECG) at therapeutic and supratherapeutic doses.
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.
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