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

End Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01568775
• Other study ID #: CSPP100A2262
• Secondary ID: 2009-014358-13
• Status: Completed
• Phase: Phase 1
• First received: March 29, 2012
• Last updated: March 29, 2012
• Start date: June 2010
• Est. completion date: September 2010

Study information

• Verified date: March 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• Aliskiren
All patient and subjects received single dose of aliskiren 300 mg in treatment period.

Locations

Country	Name	City	State
Germany	Charité Universitätsmedizin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Primary	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)	No
Secondary	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)	No
Secondary	Number of patients with adverse events, serious adverse events and death		maximum 30 days	Yes