Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of the blood pressure medication, aliskiren, in heart transplant patients. In terms of safety, the investigators will evaluate the blood levels of aliskiren and determine if aliskiren alters the blood levels of the anti-rejection medication, cyclosporine, in these patients. In terms of efficacy, the investigators will determine how well aliskiren lowers blood pressure in heart transplant patients.

Detailed Description
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Hypertension is a major complication following cardiac transplantation, with a prevalence of 93% at 5 years post-transplant. Post-cardiac transplant hypertension is due to multiple factors such as use of cyclosporine, chronic kidney disease, and denervation. Hypertension in this population is difficult to treat, and most patients require therapy with multiple antihypertensive agents in order to achieve adequate blood pressure control. Aliskiren, a direct renin inhibitor, is a novel antihypertensive agent with a unique mechanism of action and potent blood pressure-lowering effects. As such, aliskiren is an attractive treatment option for post-cardiac transplant hypertension. This study will characterize the pharmacokinetic drug-drug interaction profile, pharmacodynamics, and safety of aliskiren 75 mg daily (low-dose) and 150 mg daily, when given in combination with cyclosporine, in cardiac transplant patients.

Official Title
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Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation

Conditions
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Hypertension, Cardiac Transplantation

Intervention / Treatment
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* Drug: Aliskiren


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6 months or more since cardiac transplant Clinically stable from a transplant perspective Maintained on a stable immunosuppressant regimen containing cyclosporine + an antiproliferative agent (e.g., azathioprine, mycophenolate), +/- an oral steroid Hypertension, as defined by a seated average systolic blood pressure of ≥ 140 mm Hg and a seated average diastolic blood pressure of ≥ 90 mm Hg, based on 3 separate measurements, spaced 2 minutes apart. Exclusion Criteria: Clinical instability from a cardiac transplant perspective Contraindications to aliskiren therapy Conditions that may increase the risk of aliskiren adverse effects Severe hypertension Concomitant medications known to increase or decrease aliskiren plasma exposure.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows | Drug: Aliskiren<br>* Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows<br>* Other names: Neoral (cyclosporine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC) | The study was stopped due to difficulty finding patients who met the strict inclusion criteria. Only one patient was started on the study drug. as a result we did not analyze any cyclosporine PK (e.g.(AUCs) for this study. | 7 days, 14 days, 30 days (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aliskiren Plasma Concentrations | Maximum plasma concentration; area under the concentration-time curve, half-life, oral clearance The study was stopped due to difficulty finding patients who met the strict inclusion criteria. Only one patient was started on the study drug. as a result we did not analyze any PK (e.g.(AUCs) for this study. | 2 weeks | 
| Blood Pressure | The study was stopped due to difficulty finding patients who met the strict inclusion criteria. Only one patient was started on the study drug. as a result we did not analyze any blood pressure for this study. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Cardiac transplantation, Aliskiren, Cyclosporine