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An Open-label, Parallel-group Study to Determine the Pharmacokinetics of a Single Dose of AFQ056 in Subjects With Renal Impairment Compared to Healthy Subjects

Primary Purpose

Mild Moderate, or Severe Renal Impairment

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
AFQ056
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Mild Moderate focused on measuring Renal impairment,, pharmacokinetics,, safety

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed.
  • Female subjects must be of non-child bearing potential as defined as postmenopausal females with no regular menstrual bleeding for at least 1 year prior to inclusion
  • Body weight: ≥50kg; BMI: 18-34 kg/m2
  • Ability to communicate well with the investigator and comply with the requirements of the study.

For subjects with renal impairment only

  • No current clinically significant disease (other than renal impairment), except for stable underlying disease that caused renal impairment, as determined by clinical history and physical examination.
  • MDRD-calculated eGFR of <90 mL/min/1.73 m2 based on serum creatinine
  • Vital signs (after 3 minutes resting measured in the supine position) should be within normal ranges as deemed by the Investigator.

For healthy subjects only

  • No current clinically significant disease as determined by clinical history and physical examination.
  • MDRD-calculated eGFR of ≥90 mL/min/1.73 m2 based on serum creatinine.
  • Vital signs (after 3 minutes resting measured in the supine position) should be within normal ranges as deemed by the Investigator.

Exclusion Criteria:

  • Pregnant or nursing (lactating) females
  • Use of any prescription or over-the-counter (OTC) drugs, herbal (e.g. St. John's wort) ordietary supplements (e.g. broccoli, vitamins) within three weeks or five half lives(whichever is longer) prior to dosing with AFQ056 until study completion. This does not include drugs that are used as (symptomatic) treatment of renal impairment (e.g. antihypertensive and antidiabetic drugs) provided such drugs are:

    • used at the same dose within three weeks or five half lives (whichever is longer) prior to dosing with AFQ056 until study completion.
    • not known as inhibitors or inducers of CYP1A1, 1A2, 2C8, 2C9, 2C19, 3A4, 3A5 gp).
  • Participation in any clinical investigation or use of any investigational drug within 30 days or five (5) half-lives of a given investigational drug (whichever period is longer); or longer if required by local regulations prior to screening until study completion
  • Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
  • History of renal transplantation
  • History or presence of prolonged QTc interval (males: >450ms; females: > 470 ms), 2nd or 3rd degree AV-block or any other clinically significant ECG abnormalities as determined by medical history and 12-lead ECG recordings at screening and baseline 1.
  • History or presence of any clinically significant disease of any major system organ class, within the past 2 years prior to screening, except for renal impairment and underlying diseases causing renal impairment for the subject belonging to the renal impairment groups.
  • Subjects undergoing any method of dialysis (hemodialysis or peritoneal dialysis)
  • History of or ongoing active substance abuse (including alcohol) within the past 2 years.
  • Smokers (use of tobacco products in the previous 3 months). Urine cotinine levels will be measured during Screening and at Baseline for all subjects. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥ 500 ng/mL at screening

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All study subjects

Arm Description

Outcomes

Primary Outcome Measures

Measure: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Measure: Area under the curve from time zero to the last measurable concentration sampling time (Tlast) [mass x time x volume-1] (AUClast)
Measure: Maximum observed plasma concentration (Cmax)
Measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measure: Terminal elimination half-life (T1/2)
Measure: The apparent systemic (or total body) clearance from plasma following extravascular administration [volume / time] (CL/F)
Measure: The apparent volume of distribution during the terminal elimination phase following oral administration [volume] (Vz/F)
Measure: Amount of drug excreted into the urine from time zero to time't' where t is a defined time point after administration [mass units or % of dose] (Ae0-t)
Measure: The renal clearance from plasma [volume / time] (CLr)

Secondary Outcome Measures

Physical examination
Measure: Vital signs and body measurements
Measure: ECG
Measure: pulse oximetry
Measure: hematology
Measure: blood chemistry
Measure: urinalysis
Measure: AE (adverse events) monitoring
SAE (serious adverse events) monitoring

Full Information

First Posted
September 9, 2011
Last Updated
December 6, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01442259
Brief Title
An Open-label, Parallel-group Study to Determine the Pharmacokinetics of a Single Dose of AFQ056 in Subjects With Renal Impairment Compared to Healthy Subjects
Official Title
An Open-label, Parallel-group Study to Determine the Pharmacokinetics of a Single Dose of AFQ056 in Subjects With Mild, Moderate or Severe Renal Impairment Compared to Age, Sex, and Body Weight-matched Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
The aim of this study was to characterize the pharmacokinetics and safety of AFQ056 in subjects with a different degree of renal impairment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Moderate, or Severe Renal Impairment
Keywords
Renal impairment,, pharmacokinetics,, safety

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All study subjects
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AFQ056
Primary Outcome Measure Information:
Title
Measure: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose
Title
Measure: Area under the curve from time zero to the last measurable concentration sampling time (Tlast) [mass x time x volume-1] (AUClast)
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose
Title
Measure: Maximum observed plasma concentration (Cmax)
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose
Title
Measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose
Title
Measure: Terminal elimination half-life (T1/2)
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose
Title
Measure: The apparent systemic (or total body) clearance from plasma following extravascular administration [volume / time] (CL/F)
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose
Title
Measure: The apparent volume of distribution during the terminal elimination phase following oral administration [volume] (Vz/F)
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose
Title
Measure: Amount of drug excreted into the urine from time zero to time't' where t is a defined time point after administration [mass units or % of dose] (Ae0-t)
Time Frame
4 days
Title
Measure: The renal clearance from plasma [volume / time] (CLr)
Time Frame
4 days
Secondary Outcome Measure Information:
Title
Physical examination
Time Frame
Screening, Day -1, Day 8 +/- 2 days
Title
Measure: Vital signs and body measurements
Time Frame
Screening, Day -1, Day 1, Day 8 +/- 2 days
Title
Measure: ECG
Time Frame
Screening, Day -1, Day 1, Day 8 +/- 2 days
Title
Measure: pulse oximetry
Time Frame
Screening, Day -1, Day 1, Day 8 +/- 2 days
Title
Measure: hematology
Time Frame
Screening, Day -1, Day 4, Day 8 +/- 2 days
Title
Measure: blood chemistry
Time Frame
Screening, Day -1, Day 2, Day 4, Day 8 +/- 2 days
Title
Measure: urinalysis
Time Frame
Screening, Day -1, Day 4, Day 8 +/- 2 days
Title
Measure: AE (adverse events) monitoring
Time Frame
During the study (up to 10 days)
Title
SAE (serious adverse events) monitoring
Time Frame
During the study (up to 10 days) and up to 30 days after study completion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Female subjects must be of non-child bearing potential as defined as postmenopausal females with no regular menstrual bleeding for at least 1 year prior to inclusion Body weight: ≥50kg; BMI: 18-34 kg/m2 Ability to communicate well with the investigator and comply with the requirements of the study. For subjects with renal impairment only No current clinically significant disease (other than renal impairment), except for stable underlying disease that caused renal impairment, as determined by clinical history and physical examination. MDRD-calculated eGFR of <90 mL/min/1.73 m2 based on serum creatinine Vital signs (after 3 minutes resting measured in the supine position) should be within normal ranges as deemed by the Investigator. For healthy subjects only No current clinically significant disease as determined by clinical history and physical examination. MDRD-calculated eGFR of ≥90 mL/min/1.73 m2 based on serum creatinine. Vital signs (after 3 minutes resting measured in the supine position) should be within normal ranges as deemed by the Investigator. Exclusion Criteria: Pregnant or nursing (lactating) females Use of any prescription or over-the-counter (OTC) drugs, herbal (e.g. St. John's wort) ordietary supplements (e.g. broccoli, vitamins) within three weeks or five half lives(whichever is longer) prior to dosing with AFQ056 until study completion. This does not include drugs that are used as (symptomatic) treatment of renal impairment (e.g. antihypertensive and antidiabetic drugs) provided such drugs are: used at the same dose within three weeks or five half lives (whichever is longer) prior to dosing with AFQ056 until study completion. not known as inhibitors or inducers of CYP1A1, 1A2, 2C8, 2C9, 2C19, 3A4, 3A5 gp). Participation in any clinical investigation or use of any investigational drug within 30 days or five (5) half-lives of a given investigational drug (whichever period is longer); or longer if required by local regulations prior to screening until study completion Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation. History of renal transplantation History or presence of prolonged QTc interval (males: >450ms; females: > 470 ms), 2nd or 3rd degree AV-block or any other clinically significant ECG abnormalities as determined by medical history and 12-lead ECG recordings at screening and baseline 1. History or presence of any clinically significant disease of any major system organ class, within the past 2 years prior to screening, except for renal impairment and underlying diseases causing renal impairment for the subject belonging to the renal impairment groups. Subjects undergoing any method of dialysis (hemodialysis or peritoneal dialysis) History of or ongoing active substance abuse (including alcohol) within the past 2 years. Smokers (use of tobacco products in the previous 3 months). Urine cotinine levels will be measured during Screening and at Baseline for all subjects. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥ 500 ng/mL at screening Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Kiel
Country
Germany

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=6624
Description
Results for CAFQ056A2124 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

An Open-label, Parallel-group Study to Determine the Pharmacokinetics of a Single Dose of AFQ056 in Subjects With Renal Impairment Compared to Healthy Subjects

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