A Study to Assess the Safety, Tolerability, and Effects of MK-0974 (Telcagepant) on Exercise Tolerance in Patients With Stable Angina (MK-0974-014)
Condition: Angina Pectoris; Coronary Heart Disease; Calcitonin Gene-related Peptide Receptor
MeSH terms: Heart Diseases; Angina Pectoris; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Angina, Stable
Intervention: telcagepant; Placebo to telcagepant
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: angina pectoris; coronary artery disease; calcitonin gene-related peptide; exercise tolerance,

Summary:

      This study will assess the safety of telcagepant in coronary artery disease (CAD)
      participants with stable angina during exercise treadmill testing and evaluate whether
      calcitonin gene-related peptide (CGRP) receptor antagonism by telcagepant reduces exercise
      tolerance in these participants. Primary hypothesis is that telcagepant does not
      significantly decrease exercise duration compared to placebo, as measured by a treadmill
      exercise test; that is, the true treatment difference in exercise duration (MK-0974 -
      Placebo) >= -60 seconds.
    

Eligibility criteria:

        Inclusion:

          -  Participant has clinically documented stable coronary artery disease as demonstrated
             by coronary angiography, echocardiogram, or stress test, etc., or participant is on
             stable doses of current medication for the treatment of coronary artery disease for a
             minimum of 30 days.

          -  Participant has a history of stable angina (chronic stable angina pectoris that is
             triggered by physical effort and relieved by rest and/or sublingual nitroglycerin) for
             at least 3 months prior to study start, with no intervening symptoms of unstable
             angina.

          -  Participant is able to demonstrate reproducibly positive exercise tests by completing
             treadmill tests on 2 separate days, within 1-8 days.

          -  Participant agrees to refrain from drinking alcohol from 24 hours prior to study drug
             administration, on study procedure days, and until release from the study facility.

          -  Participants agrees to refrain from smoking from midnight before study procedures
             until study procedures are complete for the day.

          -  Participant has no clinically significant abnormality on screening laboratory safety
             assessment.

          -  Participant agrees to refrain from unaccustomed strenuous physical activity from the
             prestudy (screening) visit, throughout the study, and until the post-study visit.

        Exclusion:

          -  Participant is pregnant (positive serum beta-human chorionic gonadotropin [β-hCG] test
             at prestudy), breast-feeding, or is a female expecting to conceive within the
             projected duration of the study. Postmenopausal women who are currently using hormone
             replacement therapy are excluded from participation in the study.

          -  Participant has electrocardiogram (ECG) findings that interfere with ECG
             interpretation or may cause false positive stress test (e.g., > 1 mm horizontal or
             downsloping ST-segment depression at rest in any standard electrocardiographic lead,
             Lown-Ganong-Levine syndrome, Wolff-Parkinson-White (WPW), left bundle branch block
             (LBBB), left ventricular hypertrophy (LVH) with repolarization abnormality, pectus
             excavatum, ventricular pacemaker, etc.). Note: these ECG findings may affect stress
             test results; there may be other findings that have not been included which may affect
             test results. These ECG findings are exclusions only if these findings may jeopardize
             interpretation of stress test results.

          -  Participant has heart rate-corrected QT interval (QTc) (Bazett) > 500 ms on resting
             ECG.

          -  Participant has uncontrolled high blood pressure at prestudy screening.

          -  Participant has a baseline heart rate of <40 or >96 beats per minute at screening.

          -  Participant has unstable angina, hypertrophic cardiomyopathy, valvular heart disease,
             congenital cardiac defect, severe aortic stenosis, class III or IV heart failure.

          -  Participant has diabetes and is, in the opinion of the investigator, unable to comply
             with the pre-and post-dosing fasting requirements of the study due to risks of
             hypoglycemia.

          -  Participant is unable to withhold acetohexamide, chlorpropamide, glimepride,
             glimepiride and pioglitazone, glimepride and rosiglitazone, glipizide, glipizide and
             metformin, glyburide, glyburide and metformin, tolazamide, tolbutamide, or any other
             medication, that in the opinion of the investigator is likely to result in
             hypoglycemia within 8 hours of dosing.

          -  Participant has had myocardial infarction or coronary revascularization within the
             prior 2 months.

          -  Participant has acute myocarditis or pericarditis.

          -  Participant is obese, with adipose tissue which may interfere with ECG interpretation,
             or in the opinion of the investigator, whose obesity puts the participant at medical
             risk.

          -  Participant has clinically significant hypokalemia or hypomagnesemia.

          -  Participant has a history of any illness that, in the opinion of the investigator,
             might confound the results of the study or poses an additional risk to the participant
             by their participation in the study.

          -  Participant must not have taken any of the following medications in the time frame
             specified: Participant is unable to refrain from or anticipates the use of any herbal
             remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of
             the initial dose of study drug, throughout the study (including washout intervals
             between treatments), until the post-study visit; participant is unable to refrain from
             taking a drug metabolized by cytochrome P450 3A4 (CYP3A4) until at least 48 hours post
             dose (the exact length of time a specific drug metabolized by CYP3A4 is withheld is
             dependent on the therapeutic index of the drug and the extent to which it is
             metabolized by CYP3A4); participant consumes excessive amounts of alcohol which, in
             the opinion of the investigator, puts the participant at medical risk by participating
             in the study (participant has clinical [e.g., enlarged liver] or laboratory evidence
             [e.g., elevated alanine aminotransferase (ALT)], of chronic alcoholism or drug abuse,
             in the opinion of the investigator); participants is currently a regular user
             (including: recreational use") of any illicit drugs or has a history of drug
             (including alcohol) abuse within approximately 6 months; participant has taken potent
             CYP3A4 inhibitors, including but not limited to cyclosporine, systemic
             (oral/intravenous) itraconazole, ketoconazole, erythromycin, clarithromycin,
             telithromycin, nefazodone, human immunodeficiency virus (HIV) protease inhibitors
             within 1 month prior to dosing with MK-0974 or placebo and throughout the study
             period; participant has taken moderate CYP3A4 inhibitors, including but not limited to
             verapamil, diltiazem, fluconazole, fluvoxamine, fluoxetine, aprepitant within 2 weeks
             prior to dosing with MK-0974 or placebo and throughout the study period; participant
             has taken potent CYP3A4 inducers, including but not limited to rifampicin, rifabutin,
             carbamazepine, phenytoin, barbiturates, systemic glucocorticoids (replacements and
             inhaled are permitted), nevirapine, efavirenz, pioglitazone, primidone, St. John's
             wort within 1 month prior to dosing MK-0974 or placebo and throughout the study
             period; participant has taken triptans, ergot alkaloids within 48 hours prior to
             dosing MK-0974 or placebo and throughout the study period; participant has taken
             digoxin, medications that prolong QTc interval such as Class IA and Class III
             anti-arrhythmics (quinidine, procainamide, amiodarone, sotalol, etc), Seldane
             (terfenadine), Hismanal (astemizole), Propulsid (cisapride) within 1 month prior to
             dosing MK-0974 or placebo and throughout the study period; participant has received an
             investigational medication within 4 weeks prior to the prestudy (screening) visit.

          -  Participant has a history of multiple and/or severe allergies, or has had an
             anaphylactic reaction or intolerability to prescription or non-prescription drugs or
             food.

          -  There is any concern by the investigator regarding the safe participation of a
             participant in the study, or for any other reason the investigator considers the
             participant inappropriate to participate in the study.