Last updated: 11/07/2018 08:03:17

A study to assess the effects of GSK573719/VI combination and GSK573719 monotherapy in subjects with moderate hepatic impairment and matched healthy volunteers

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GSK study ID
114637
See study documents
Clinicaltrials.gov ID
NCT01577680
EudraCT ID
2011-005454-61
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: An open-label, non-randomized, pharmacokinetic and safety study of single dose GSK573719 + GW643444 (VI) combination and repeat doses of GSK573719 in healthy subjects and in subjects with moderate hepatic impairment
Trial description: 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.
Primary purpose:
Basic Science
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

GSK573719 and vilanterol pharmacokinetics

Timeframe: 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

Timeframe: 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:

Urine pharmacokinetics for GSK573719 (Treatment Period 1)

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

Urine pharmacokinetics for GSK573719 (Treatment Period 2)

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

Measurement of vital signs

Timeframe: 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

Timeframe: 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

Timeframe: 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)

12-lead ECG measurements

Timeframe: 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, 4hrs, 12hrs, 24hrs

Interventions:
  • Drug: Inhaled GSK573719/vilanterol
  • Drug: Inhaled GSK573719
    • Enrollment:
    18
    Primary completion date:
    Not applicable
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Mehta R, Hardes K, Kelleher D, Preece A, Tombs L, Brealey N.Effect of moderate hepatic impairment on the pharmacokinetic properties and tolerability of umeclidinium and vilanterol in inhalational umeclidinium monotherapy and umeclidinium/vilanterol combination therapy: an open-label, nonrandomized study.Clin Ther.2014;36(7):1016-1027
    Medical condition
    Pulmonary Disease, Chronic Obstructive
    Product
    umeclidinium bromide, umeclidinium bromide/vilanterol, vilanterol
    Collaborators
    Not applicable
    Study date(s)
    March 2012 to June 2012
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 70 years
    Accepts healthy volunteers
    Yes
    • 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:
    • 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.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • 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.
    Exclusion criteria:
    • 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
    • Subjects with any predisposing condition that might interfere with the absorption, distribution, metabolism or excretion of drugs or any previous gastrointestinal (GI) surgery condition which the investigator considers sufficiently significant to interfere with the conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
    • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
    • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
    • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units for males or 14 units for females
    • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication Hepatically impaired subjects:
    • If in the opinion of the examining physician, an unstable cardiovascular, renal, pulmonary, endocrine, metabolic, neurological, haematological or gastrointestinal condition is present or any other significant medical condition which the investigator considers sufficiently serious to interfere with the conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
    • Severe ascities (Child-Pugh ascites score of 3) upon clinical exam, including physical exam and abdominal ultrasound at screening. Subjects identified to have moderate ascities by ultrasound examination may be included at the discretion of the Investigator with prior agreement from the sponsor.
    • History of oesophageal bleeding within the last 6 months before dosing.
    • Significant hepatic encephalopathy, degree of CNS impairment or other signs of hepatic function deterioration which the investigator considers sufficiently serious to interfere with the informed consent, conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
    • Patients at risk of requiring a transfusion during the study period, or has haemoglobin less than 9 g/dL
    • Evidence of current significant infection
    • Subjects who develop symptoms such as infections or haemorrhage between screening and dosing must not be included in the study
    • Fluctuating or rapidly deteriorating hepatic function
    • Subjects with significant renal insufficiency as defined by estimated creatinine clearance of less than 50 ml/min, using the Cockcroft and Gault equation
    • Subjects with a diagnosis of primary biliary disease such as cholestasis or sclerosing cholangitis
    • Subjects who need to take any concomitant medication, either prescribed or overthe- counter, which may in the opinion of the Investigator, interfere in any way with the study procedure or be a safety concern. In particular subjects taking medications that significantly inhibit P450 CYP3A4 (e.g. ketoconazole) must not be included in this study
    • Subjects who, within the past six months, have had a history of significant drug abuse or alcohol abuse.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Budapest, Hungary, H-1115
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Bratislava, Slovakia, 831 01
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
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    Scientific result summary
    Available language(s): English
    Download document(s)
    Protocol
    Available language(s): English
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    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    Study complete
    Actual primary completion date
    Not applicable
    Actual study completion date
    2012-29-06

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

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