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

NCT01613690 | Completed Phase 1

• 1 other identifier: CNVA237A2105
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Impairment

Keywords

Renal impairment; NVA237; Pharmacokinetics

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (3)

• Change in effect of dialysis in End-stage subjects requiring dialysis (ESRD) using PK parameter Cmax

  Day 1 of each treatment period

• Change in effect of dialysis in End-stage subjects requiring dialysis using PK parameter AUClast

  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

  Reviewed during each study visit

Study Arms (5)

Healthy volunteers

EXPERIMENTAL

control group receiving 100 μg NVA237

Drug: NVA237

Mild renal impairment

EXPERIMENTAL

(eGFR 50-80 mL/min/1.73m2) receiving 100 μg NVA237

Drug: NVA237

Moderate renal impairment

EXPERIMENTAL

(eGFR 30-49 mL/min/1.73m2) receiving 100 μg NVA237

Drug: NVA237

Severe renal impairment

EXPERIMENTAL

(eGFR \<30 mL/min1.73m2) receiving 100 μg NVA237

Drug: NVA237

End-stage subjects requiring dialysis (ESRD)

EXPERIMENTAL

receiving 100 μg NVA237

Drug: NVA237

Interventions

NVA237 DRUG

NVA237 is administered via a BREEZHALER device

End-stage subjects requiring dialysis (ESRD); Healthy volunteers; Mild renal impairment; Moderate renal impairment; Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Moscow, Russia

Location

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Glycopyrrolate

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 7, 2012
• Study Start: June 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: December 19, 2020

Record last verified: 2012-06

Locations

RU (1)