An Interventional Study to Evaluate the Effect of Ivabradine on Exercise Capacity in Heart Transplant Recipients

- Subject has provided informed consent/assent prior to initiation of any study-specific activities/procedures - Male or female, ≥ 18 to ≤ 70 years of age at signing of informed consent - History of heart transplantation within 1 to 4 years from screening - Sinus rhythm and elevated resting HR > 95 bpm at screening (ECG) - Able to perform exercise testing as required per protocol, per the investigator, at time of screening - Peak VO2 < 70% of the predicted normal value for age and gender with respiratory exchange ratio (RER) ≥ 1.05, from a CPET conducted during screening

- Participation in a cardiac rehabilitation program during the study period - Treatment for heart transplant rejection within the previous 3 months before screening - Severe allograft vasculopathy limiting the tolerance of CPET at time of screening - During CPET at screening, significant adverse finding (eg, exercise-induced early ischemic changes, abnormal blood pressure response, unexpected arrhythmia or other serious finding) that precludes safe participation in the study, per investigator - Sick sinus syndrome, sinoatrial block and/or third degree atrioventricular block, unless a functioning demand pacemaker is present, or pacemaker dependency at screening - Resting systolic blood pressure >160 mmHg or <100 mmHg, or diastolic blood pressure >90 mmHg at screening - History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion - Presence of clinically meaningful acute or chronic infection, per investigator, at screening - Major medical event or procedure (as determined by investigator) within 3 months prior to screening - Previously received ivabradine after heart transplantation (prior to the participation in this study) - Subjects taking QT prolonging medicinal products for cardiovascular (eg, but not limited to, quinidine, disopyramide, bepridil, sotalol, ibutilide) or non-cardiovascular disease (eg, but not limited to, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, intravenous (IV) erythromycin) - Subjects should not be receiving beta-blockers, diltiazem, or verapamil for at least 7 days before screening - Subjects exposed to a strong Cytochrome P450 3A4 (CYP3A4) inhibitor (examples of strong CYP3A4 inhibitors include; azole antifungals [eg, itraconazole], macrolide antibiotics [eg, clarithromycin, telithromycin], human immunodeficiency virus protease inhibitors, [eg, nelfinavir], and nefazodone]) within 14 days prior to screening, or to a strong CYP3A4 inducer (examples of CYP3A4 inducers include; St. John’s wort, rifampicin, barbiturates, and phenytoin) within 28 days prior to screening - Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. - Hemoglobin < 8 g/dL at screening (or within 3 months prior to screening if no clinically meaningful event, as determined by the investigator, has occurred in that period) and not expected to receive blood transfusion during the study - Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease [MDRD] equation) at screening (or within 3 months prior to screening) - Subject has known sensitivity to any of the products to be administered during dosing - Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 2 weeks after the last dose of investigational product - Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 2 weeks after the last dose of investigational product. Refer to Section 12.5 for additional contraceptive information - Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a serum pregnancy test