Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01235910
• Collaborator: American Heart Association (Other)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 19.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Cardiac Transplantation	Drug: Aliskiren	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows	Drug: Aliskiren; Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows; Other Names: Tekturna (aliskiren) Neoral (cyclosporine)

Outcome Measures

Primary Outcome Measures

1. Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC) [7 days, 14 days, 30 days (End of Study)]

   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.

Secondary Outcome Measures

1. Aliskiren Plasma Concentrations [2 weeks]

   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. Blood Pressure [2 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• American Heart Association

Investigators

• Principal Investigator: Christina L Aquilante, Pharm.D., University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01235910
• Other Study ID Numbers: 10-0746
• First Posted: Nov 7, 2010
• Last Update Posted: Jun 29, 2018
• Last Verified: May 1, 2018

• Keywords provided by University of Colorado, Denver: Hypertension; Cardiac transplantation; Aliskiren; Cyclosporine
• Additional relevant MeSH terms: Hypertension; Cyclosporine; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Aliskiren
Arm/Group Description	Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows Aliskiren: Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Aliskiren
Arm/Group Description	Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows Aliskiren: Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (0)
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC)
Description	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.
Time Frame	7 days, 14 days, 30 days (End of Study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren
Arm/Group Description	Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows Aliskiren: Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Measure Participants	1
Number [ng*h/ml/mg]	NA

2. Secondary Outcome

Title	Aliskiren Plasma Concentrations
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren
Arm/Group Description	Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows Aliskiren: Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Measure Participants	1
Number [ng*h/ml/mg]	NA

3. Secondary Outcome

Title	Blood Pressure
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren
Arm/Group Description	Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows Aliskiren: Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Measure Participants	1
Number [mmHg]	NA

Adverse Events

Arm/Group Title	Aliskiren
Arm/Group Description	Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows Aliskiren: Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
All Cause Mortality
	Aliskiren
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aliskiren
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

The study was stopped due to difficulty finding patients who met the strict inclusion/exclusion criteria. Only one patient was started on study drug.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.