Comparing the Pharmacokinetics, Safety and Tolerability of NVA237 in Renal Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01613690
First received: June 5, 2012
Last updated: NA
Last verified: June 2012
History: No changes posted
  Purpose

The purpose of this study is to see how the body processes and gets rid of NVA237 in people who have impaired kidney function compared to people whose kidney function is normal.


Condition Intervention Phase
Renal Impairment
Drug: NVA237
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: An Open Label, Non-randomized, Parallel-group Study to Characterize and Compare the Pharmacokinetics, Safety, and Tolerability of a Single Dose of NVA237 in Subjects With Mild, Moderate, Severe and End-stage Renal Impairment With That in Matched Healthy Control Subjects

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Concentration of NVA2105 using PK parameter of primary interest - area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter of primary interest - maximum plasma concentration (Cmax) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter of primary interest - renal clearance (CLR) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter of secondary interest - time to Cmax (Tmax) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter of secondary interest - AUC extrapolated to infinity (AUCinf) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter of secondary interest - terminal elimination half-life, determined from plasma concentrations and urinary excretion rates (T1/2) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter of secondary interest - apparent systemic clearance (CL/F) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter - amount excreted into the urine from time 0 to 96 h post-dose (Ae0-96h) [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter - T1/2 [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237

  • Concentration of NVA2105 using PK parameter - CLR [ Time Frame: Day 1, 2, 3, 4 and 5 ] [ Designated as safety issue: No ]
    Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237


Secondary Outcome Measures:
  • Change in effect of dialysis in End-stage subjects requiring dialysis (ESRD) using PK parameter Cmax [ Time Frame: Day 1 of each treatment period ] [ Designated as safety issue: Yes ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Change in effect of dialysis in End-stage subjects requiring dialysis using PK parameter AUClast [ Time Frame: Day 1 of each treatment period ] [ Designated as safety issue: Yes ]
    Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237

  • Safety and tolerability of a single inhalation dose of 100μg NVA237 in subjects with mild, moderate, severe, and end-stage renal impairment [ Time Frame: Reviewed during each study visit ] [ Designated as safety issue: Yes ]
    Adverse events will be based on evaluation of physical signs, electrocardiograms and clinical laboratory assessments


Enrollment: 48
Study Start Date: June 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy volunteers
control group receiving 100 μg NVA237
Drug: NVA237
NVA237 is administered via a BREEZHALER device
Experimental: Mild renal impairment
(eGFR 50-80 mL/min/1.73m2) receiving 100 μg NVA237
Drug: NVA237
NVA237 is administered via a BREEZHALER device
Experimental: Moderate renal impairment
(eGFR 30-49 mL/min/1.73m2) receiving 100 μg NVA237
Drug: NVA237
NVA237 is administered via a BREEZHALER device
Experimental: Severe renal impairment
(eGFR <30 mL/min1.73m2) receiving 100 μg NVA237
Drug: NVA237
NVA237 is administered via a BREEZHALER device
Experimental: End-stage subjects requiring dialysis (ESRD)
receiving 100 μg NVA237
Drug: NVA237
NVA237 is administered via a BREEZHALER device

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and female subjects age 18 to 70 years of age inclusive.
  • Female subjects of childbearing potential must be using two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through study completion.
  • Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 17 to 35 kg/m2.
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent
  • For renal insufficient subjects only - Subjects must have stable renal disease without evidence of renal progressive disease (for the purpose of this study stable renal disease will be defined as no significant change for 12 weeks).
  • For health subjects only - A serum creatinine within the normal range and an eGFR >80 mL/min/1.73 m2.
  • For health subjects only - Matched to at least one renal impaired subjects undergoing study by age (±5 years), sex and weight (±10% BMI).

Exclusion Criteria:

  • Smokers (use of tobacco products in the previous 3 months). Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥ 500 ng/mL. If non-smoking subject are too difficult to recruit, smokers may be allowed to participate in the study provided they commit to smoke no more than 10 cigarettes/day during the days of PK-assessment
  • For healthy subjects, use of any prescription drugs, herbal and fitness/bodybuilding/athletic performance-enhancing supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing
  • Recent (within the last three [3] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting (unless related to water withdrawal during dialysis), palpitations, etc).
  • Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
  • History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study.
  • Total WBC count which falls outside the range of 3000-12,000/μL, or platelets <100,000/μl at screening.
  • History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.

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: NCT01613690

Locations
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation
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: NCT01613690     History of Changes
Other Study ID Numbers: CNVA237A2105
Study First Received: June 5, 2012
Last Updated: June 5, 2012
Health Authority: Russia: Ministry of Health of the Russian Federation

Keywords provided by Novartis:
Renal impairment
NVA237
Pharmacokinetics

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on August 19, 2014