Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01442259
First received: September 9, 2011
Last updated: October 21, 2011
Last verified: October 2011
  Purpose

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


Condition Intervention Phase
Mild, Moderate,
or Severe Renal Impairment
Drug: AFQ056
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
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

Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Measure: Maximum observed plasma concentration (Cmax) [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 48, 72 hours post dose ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Measure: The renal clearance from plasma [volume / time] (CLr) [ Time Frame: 4 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Physical examination [ Time Frame: Screening, Day -1, Day 8 +/- 2 days ] [ Designated as safety issue: Yes ]
  • Measure: Vital signs and body measurements [ Time Frame: Screening, Day -1, Day 1, Day 8 +/- 2 days ] [ Designated as safety issue: Yes ]
  • Measure: ECG [ Time Frame: Screening, Day -1, Day 1, Day 8 +/- 2 days ] [ Designated as safety issue: Yes ]
  • Measure: pulse oximetry [ Time Frame: Screening, Day -1, Day 1, Day 8 +/- 2 days ] [ Designated as safety issue: Yes ]
  • Measure: hematology [ Time Frame: Screening, Day -1, Day 4, Day 8 +/- 2 days ] [ Designated as safety issue: Yes ]
  • Measure: blood chemistry [ Time Frame: Screening, Day -1, Day 2, Day 4, Day 8 +/- 2 days ] [ Designated as safety issue: Yes ]
  • Measure: urinalysis [ Time Frame: Screening, Day -1, Day 4, Day 8 +/- 2 days ] [ Designated as safety issue: Yes ]
  • Measure: AE (adverse events) monitoring [ Time Frame: During the study (up to 10 days) ] [ Designated as safety issue: Yes ]
  • SAE (serious adverse events) monitoring [ Time Frame: During the study (up to 10 days) and up to 30 days after study completion ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: January 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All study subjects Drug: AFQ056

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01442259

Locations
Germany
Novartis Investigative Site
Kiel, Germany
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01442259     History of Changes
Other Study ID Numbers: CAFQ056A2124, 2010-022738-94
Study First Received: September 9, 2011
Last Updated: October 21, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Renal impairment,
pharmacokinetics,
safety

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on November 25, 2014