A Study to Assess the Effects of GSK573719/VI Combination and GSK573719 Monotherapy in Subjects With Moderate Hepatic Impairment and Matched Healthy Volunteers

NCT01577680 | Completed Phase 1

• 1 other identifier: 114637
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

healthy subjects; pharmacokinetics; vilanterol; tolerability; safety; hepatic impairment; GW642444; GSK573719

Outcome Measures

Primary Outcomes (2)

• GSK573719 and vilanterol pharmacokinetics

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

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

• GSK573719 pharmacokinetics

  Including AUC(0-t), AUC(0-t'), Cmax, tmax, AUC(0-24), AUC(0-infinity), tlast, t1/2 (following single and repeat dose administration)

  Treatment Period 2 (Day 1 and 7): Pre-dose, 5 mins, 15 mins, 30 mins, 1 hr, 2hrs, 4 hrs, 8 hrs, 12hrs, 16 hrs, 24 hrs (and 36 hrs on Day 7 only)

Secondary Outcomes (6)

• Urine pharmacokinetics for GSK573719 (Treatment Period 1)

  0-4hrs, 4-8hrs, 8-12hrs and 12-24hrs

• Urine pharmacokinetics for GSK573719 (Treatment Period 2)

  Days 1 and 7: 0-4hrs, 4-8hrs, 8-12hrs, 12-24hrs (and 24-36hrs on Day 7 only)

• Measurement of vital signs

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

• Adverse Events

  Adverse events will be recorded from the start of dosing to follow-up (7 to 14 days after last dose), an average expected duration of 4 weeks

• Clinical Laboratory Safety Tests

  Screening (up to 21 days before dosing), Treatment Period 1: pre-dose, 24 hrs, Treatment Period 2 (Day 1 and 7): pre-dose, 24 hrs, Day 4 hepatic subjects only, Follow-up (7 to 14 days after last dose)

Study Arms (2)

Moderate Hepatic Impairment

EXPERIMENTAL

Approximately 9 subjects will complete each of these treatment arms

Drug: Inhaled GSK573719/vilanterol; Drug: Inhaled GSK573719

Matched Healthy Volunteers

EXPERIMENTAL

Matched to the moderate hepatic impairment subjects based on gender, ethnicity, body mass index (+/-15%) and age (+/-5 years) Approximately 9 subjects will complete each of these treatment arms

Drug: Inhaled GSK573719/vilanterol; Drug: Inhaled GSK573719

Interventions

Inhaled GSK573719/vilanterol DRUG

All subjects will receive a single dose of GSK573719/VI (125mcg/25mcg) in Treatment Period 1

Matched Healthy Volunteers; Moderate Hepatic Impairment

Inhaled GSK573719 DRUG

All subjects will receive GSK573719 (125mcg) once daily for seven days in Treatment Period 2

Matched Healthy Volunteers; Moderate Hepatic 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 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 Child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in the protocol
• Body weight of greater than or equal to 45 kg and body mass index 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.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form Healthy Subjects
• ALT, alkaline phosphatase and bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN)
• Healthy as determined by a responsible and experienced physician Hepatically Impaired Subjects
• Moderately hepatically impaired - subjects must have a known medical history of liver disease with or without a known history of alcohol abuse, and a Child-Pugh score of 7-9 points
• Subjects with no significant abnormality, apart from impaired hepatic function and related symptoms, or clinical examination.

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.
• 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.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• 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
• 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.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
• The subject is unable to use the novel dry powder inhaler correctly Healthy Subjects

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Budapest, H-1115, Hungary

Location

GSK Investigational Site

Bratislava, 831 01, Slovakia

Location

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 114637 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

vilanterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: April 16, 2012
• Study Start: March 5, 2012
• Primary Completion: June 29, 2012
• Study Completion: June 29, 2012
• Last Updated: July 25, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); SL (1)