Pharmacokinetics and Safety of Alisporivir in Subjects With End Stage Renal Disease on Hemodialysis Compared to Healthy Subjects

An Open-label Study to Evaluate the Pharmacokinetics and Safety of a Single Oral Dose of Alisporivir (DEB025) in Subjects With End Stage Renal Disease on Hemodialysis Compared to Matched Healthy Subjects

The primary objective of the study was to compare the single dose pharmacokinetics of alisporivir in subjects with end stage renal disease (ESRD) on hemodialysis to those of matched healthy subjects. The secondary objective was to evaluate the safety and tolerability of a single dose of alisporivir when administered to subjects with ESRD.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic
• Intervention / Treatment: Drug: Alisporivir

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provides written informed consent before any assessment is performed
• Matched healthy participants are in good health as determined by past medical history, physical examination, vital signs, laboratory tests, and other assessments
• ESRD participants are on a protocol-defined stable hemodialysis regimen and have no evidence of hepatic decompensation, with vital signs and other tests within protocol-specified limits
• Weighs at least 50 kg
• Is able to communicate well with the investigator, to understand and comply with the requirements of the study.

Exclusion Criteria:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff;
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);
  3. the analysis of results

Study Plan

How is the study designed?

Design Details

• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: End stage renal disease participants; End stage renal disease (ESRD) participants received a single 400 mg (2 x 200 mg capsules) oral dose of alisporivir with food at any time during the 2 hours after completion of hemodialysis on Day 1.	Drug: Alisporivir; Alisporivir supplied as 200 mg oral capsules in blister packs (7 units per blister pack); Other Names: DEB025
ACTIVE_COMPARATOR: Matched healthy participants; Healthy participants (matched to those with end stage renal disease by sex, age, weight, and smoking status), received a single 400 mg (2 x 200 mg capsules) oral dose of alisporivir with food on Day 1.	Drug: Alisporivir; Alisporivir supplied as 200 mg oral capsules in blister packs (7 units per blister pack); Other Names: DEB025

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Observed maximum plasma concentration of alisporivir following drug administration [mass / volume] (Cmax)	Pre-dose (0 hours) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 65 hours post-dose
Area under the plasma concentration-time curve for alisporivir from time zero to time 'infinity' [mass x time / volume] (AUCinf)	Pre-dose (0 hours) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 65 hours post-dose
Area under the plasma concentration-time curve for alisporivir from time zero to the time of the last quantifiable concentration [mass x time / volume] (AUClast)	Pre-dose (0 hours) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 65 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to reach peak or maximum concentration of alisporivir following drug administration [time] (Tmax)	Pre-dose (0 hours) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 65 hours post-dose
The terminal elimination half-life [time] (T1/2) for alisporivir	Pre-dose (0 hours) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 65 hours post-dose
Apparent systemic (or total body) clearance from plasma following extravascular administration of alisporivir [volume / time] (CL/F)	Pre-dose (0 hours) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 65 hours post-dose
The apparent volume of distribution during the terminal elimination phase following extravascular administration of alisporivir [volume] (Vz/F)	Pre-dose (0 hours) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 65 hours post-dose

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: October 28, 2013
• First Posted (ESTIMATE): November 3, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 17, 2016
• Last Update Submitted That Met QC Criteria: August 16, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: CDEB025A2112