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

NCT03619187 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: 20180037
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The hypothesis is that the treatment with ivabradine will increase pVO2 after 16 weeks of treatment compared to baseline in the heart transplant recipient population with elevated resting HR.

Conditions

Heart Transplantation, Elevated Resting Heart Rate

Outcome Measures

Primary Outcomes (1)

• pVO2

  To evaluate the effect of treatment with ivabradine on exercise capacity as measured by peak oxygen consumption (pVO2)

  Week 16

Secondary Outcomes (1)

• Resting Heart Rate

  Week 16

Study Arms (1)

Single Arm

EXPERIMENTAL

Study Product

Drug: Ivabradine

Interventions

Ivabradine DRUG

Ivabradine will be provided in bottles (60 tablets per bottle) labeled ivabradine 5 mg and ivabradine 7.5 mg. The 2.5 mg dose of ivabradine will be achieved by subjects splitting the 5 mg tablets into equal halves.

Also known as: Corlanor

Single Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

Ivabradine

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, single-arm, multicenter study

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 7, 2018
• Study Start: November 2, 2018
• Primary Completion: February 19, 2020
• Study Completion: February 19, 2020
• Last Updated: November 19, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.