Pharmacokinetics, Safety and Tolerability of Aliskiren (SPP100) in Patients With End Stage Renal Disease on Hemodialysis and Matched Healthy Subjects

An Open-label, Parallel Group, Single-sequence Study to Evaluate Pharmacokinetics, Safety, and Tolerability of a Single Dose Administration of Aliskiren (SPP100) in Patients With End Stage Renal Disease on Hemodialysis and Matched Healthy Subjects

This study will assess the pharmacokinetics, safety and tolerability of aliskiren in healthy subjects and patients with End Stage Renal Disease on hemodialysis.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Aliskiren

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Charité Universitätsmedizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female subjects must be of non-child bearing potential, defined as postmenopausal women with no regular menstrual bleeding for at least 1 year prior to screening or female subjects surgically sterilized at least 6 months prior to screening. All female subjects must have negative pregnancy results at screening.
2. Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 to 30 kg/m2

3. Vital signs after 3 minutes resting in the supine position (laying down) should be within the following ranges:

   • Oral body temperature between 35.0-37.8ºC
   • Systolic blood pressure, 95-140 mmHg
   • Diastolic blood pressure, 60-90 mmHg Blood pressure and pulse will be taken again in the standing position. After 3 minutes standing, there shall be no more than a 20 mm Hg drop in systolic or 10 mmHg drop in diastolic blood pressure associated with symptomatic postural hypotension.
4. Subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study. Subjects must be able to understand and sign the written informed consent.
5. Health subjects must be in good health as determined by past medical history, physical examination, vital signed assessments, electrocardiogram, and laboratory tests at screening.
6. Patients with End Stage Renal Disease who have been on intermittent hemodialysis three times a week for at least three months and are in relatively good health.

Exclusion Criteria:

1. Smokers who report cigarette use of more than 5 cigarettes per day.
2. Use of aliskiren within 2 weeks prior to study entry.
3. Participation in any clinical investigation within 3 months prior to initial dosing.
4. Hemoglobin levels outside 11-14 mg/dL
5. A history/presence of diabetes mellitus
6. A past medical history of arrhythmias, heart failure, unstable angina pectoris, stroke, or myocardial infarction within 6 months of the start of the study.
7. A past medical history of significant electrocardiogram abnormalities.
8. Recent (within the last 3 years) and/or recurrent history/presence of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
9. Recent (within the last 3 years) and/or recurrent history/presence of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
10. Significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to aliskiren.
11. Total white blood cell (WBC) count outside the normal laboratory reference range.
12. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
13. A positive Hepatitis B surface antigen or Hepatitis C test result.
14. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening on Day -1 of each treatment period.
15. Consumption of grapefruit or grapefruit juice within 14 days prior to dosing.
16. Lactating and breastfeeding females.
17. History of head and neck angioedema.
18. Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aliskiren; All patient and subjects received single dose of aliskiren 300 mg in treatment period.	Drug: Aliskiren; All patient and subjects received single dose of aliskiren 300 mg in treatment period.; Other Names: SPP100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure: Pharmacokinetics of aliskiren: Area under the concentration-time curve from time zero to 48- hour post-dose (AUC(0-48hrs)), from time zero to the last measurable concentration sampling time (AUClast), from time zero to infinity (AUCinf)	Pharmacokinetics (concentrations of aliskiren in blood and urine) of a single dose of aliskiren in End Stage Renal Disease (ESRD) patients on hemodialysis and matched healthy subjects was analyzed.	48 hours (period 1) , 1 hour (Period 2)
Pharmacokinetics of aliskiren: Maximum (peak) observed blood and urine drug concentration (Cmax) after single dose administration	Pharmacokinetics (concentrations of aliskiren in blood and urine) of a single dose of aliskiren in End Stage Renal Disease (ESRD) patients on hemodialysis and matched healthy subjects was analyzed.	48 hours (period 1) , 1 hour (Period 2)
Pharmacokinetics of aliskiren: Time to reach maximum (peak) blood and urine drug concentration (Tmax) and elimination half-life (t1/2) after single dose administration	Pharmacokinetics (concentrations of aliskiren in blood and urine) of a single dose of aliskiren in End Stage Renal Disease (ESRD) patients on hemodialysis and matched healthy subjects was analyzed.	48 hours (period 1) , 1 hour (Period 2)

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of timing of hemodialysis on the PK of aliskiren in End Stage Renal Disease (ESRD) patients	48 hrs (Period 1), 1 hr (Period 2)
Number of patients with adverse events, serious adverse events and death	maximum 30 days

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: March 29, 2012
• First Submitted That Met QC Criteria: March 29, 2012
• First Posted (Estimate): April 2, 2012

Study Record Updates

• Last Update Posted (Estimate): April 2, 2012
• Last Update Submitted That Met QC Criteria: March 29, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; Dialysis; aliskiren; SPP100A
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: CSPP100A2262; 2009-014358-13 (EudraCT Number)