Study to Assess the Safety and PK of GSK573719 and GSK573719/GW642444(VI) Combination in Healthy Subjects and Subjects With Severe Renal Impairment

NCT01571999 | Completed Phase 1

• 1 other identifier: 114636
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 2

Brief Summary

This study will assess the safety and pharmacokinetics of inhaled GSK573719 and GSK573719/vilanterol combination in healthy subjects and in subjects with severe renal impairment. The results of the study will provide guidance on the use of this product in subjects with severe renal impairment.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

pharmacokinetics; GW642444; GSK573719; vilanterol; renal impairment; safety; COPD

Outcome Measures

Primary Outcomes (1)

• GSK573719 and vilanterol plasma pharmacokinetic parameters

  Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2

  Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 2hrs, 4hrs, 8hrs, 12hrs, 16hrs, 24hrs

Secondary Outcomes (5)

• GSK573719 urine pharmacokinetic parameters

  Treatment Period 1 and 2: 0-4hrs, 4-8hrs, 8-12hrs, 12-24hrs

• Vital Signs Measurements

  Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 4hrs, 12hrs, 24hrs, Follow-up (7 to 14 days after last dose)

• Adverse Events

  From administration of first dose until follow-up (7 to 14 days after last dose)

• Clinical Laboratory Tests

  Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 24hrs, Follow-up (7 to 14 days after last dose)

• 12-lead ECG measurements

  Screening (up to 21 days before dosing), Treatment Period 1 and 2: pre-dose, 5 mins, 15 mins, 30 mins, 1hr, 4hrs, 12hrs, 24hrs, Follow-up (7 to 14 days after last dose)

Study Arms (2)

Severe renally impaired subjects

EXPERIMENTAL

Approximately 9 subjects will complete each treatment arm

Drug: Inhaled GSK573719; Drug: Inhaled GSK573719/vilanterol

Matched healthy volunteers

EXPERIMENTAL

Matched to the severe renal impairment subjects based on gender, ethnicity, body mass index (±15%) and age (±5 years). Approximately 9 subjects will complete each treatment arm

Drug: Inhaled GSK573719; Drug: Inhaled GSK573719/vilanterol

Interventions

Inhaled GSK573719 DRUG

All subjects will receive a single dose of GSK573719 (125mcg) in treatment period 1

Matched healthy volunteers; Severe renally impaired subjects

Inhaled GSK573719/vilanterol DRUG

All subjects will receive a single dose of GSK573719 (125mcg)/vilanterol (25mcg) in treatment period 2

Matched healthy volunteers; Severe renally impaired subjects

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 or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or, child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in the protocol for an appropriate period of time prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until follow-up.
• Body weight greater than or equal to 45 kg and body mass index (BMI) within the range 18 - 33 kg/m2 (inclusive)
• Single QTcF less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block.
• Healthy Subjects:
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN)
• Creatinine clearance greater than 80mL/min calculated by the Cockcroft-Gault equation using serum creatinine
• Renally Impaired subjects:
• ALT less than 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN
• Creatinine clearance less than 30mL/min calculated by the Cockcroft-Gault equation using serum creatinine.
• Subjects with renal insufficiency must have stable renal function defined as less than or equal to a 25% difference in creatinine clearance assessed on two occasions. Renal function will be based on estimated creatinine clearance (CLcr) calculated by the Cockcroft-Gault equation using serum creatinine obtained on two occasions separated by at least 4 weeks within the last 3 months

You may not qualify if:

• Suffered a lower respiratory tract infection in the 4 weeks before the screening visit
• A supine mean heart rate outside the range 40-90 beats per minute (BPM) at screening
• A positive pre-study drug/alcohol screen
• A positive test for HIV antibody
• Current or chronic history of liver disease, including documented cirrhosis or a history consistent with a diagnosis of cirrhosis, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day
• Use of nephrotoxic medications 4 weeks before dosing
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
• Lactating females
• The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness
• Unwillingness or inability to follow the procedures outlined in the protocol
• Subject is mentally or legally incapacitated
• Subjects with smoking history of greater than 10 cigarettes per day or regular use of tobacco- or nicotine-containing products, within 6 months prior to screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Prague, 170 00, Czechia

Location

GSK Investigational Site

Budapest, H-1076, Hungary

Location

Related Publications (1)

• Mehta R, Hardes K, Brealey N, Tombs L, Preece A, Kelleher D. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study. Int J Chron Obstruct Pulmon Dis. 2014 Dec 18;10:15-23. doi: 10.2147/COPD.S68094. eCollection 2015.

  PMID: 25565796 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 114636 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Renal Insufficiency

Interventions

vilanterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2012
• First Posted: April 5, 2012
• Study Start: March 29, 2012
• Primary Completion: June 22, 2012
• Study Completion: June 22, 2012
• Last Updated: July 25, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); CZ (1)