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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: NVA237

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter of primary interest - maximum plasma concentration (Cmax)	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter of primary interest - renal clearance (CLR)	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter of secondary interest - time to Cmax (Tmax)	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter of secondary interest - AUC extrapolated to infinity (AUCinf)	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter of secondary interest - terminal elimination half-life, determined from plasma concentrations and urinary excretion rates (T1/2)	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter of secondary interest - apparent systemic clearance (CL/F)	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter - amount excreted into the urine from time 0 to 96 h post-dose (Ae0-96h)	Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter - T1/2	Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237	Day 1, 2, 3, 4 and 5
Concentration of NVA2105 using PK parameter - CLR	Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237	Day 1, 2, 3, 4 and 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in effect of dialysis in End-stage subjects requiring dialysis (ESRD) using PK parameter Cmax	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1 of each treatment period
Change in effect of dialysis in End-stage subjects requiring dialysis using PK parameter AUClast	Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237	Day 1 of each treatment period
Safety and tolerability of a single inhalation dose of 100μg NVA237 in subjects with mild, moderate, severe, and end-stage renal impairment	Adverse events will be based on evaluation of physical signs, electrocardiograms and clinical laboratory assessments	Reviewed during each study visit

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CNVA237A2105 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: June 5, 2012
• First Submitted That Met QC Criteria: June 5, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Renal impairment; NVA237
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Glycopyrrolate
• Other Study ID Numbers: CNVA237A2105