Last updated: 07/17/2024 17:31:23

Absorption & elimination of radiolabelled GSK2269557

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GSK study ID
206764
See study documents
Clinicaltrials.gov ID
NCT03315559
See results summary
EudraCT ID
2017-002347-16
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 study in healthy male subjects, to determine the excretion balance and pharmacokinetics of [14C]-GSK2269557, administered as a single intravenous microtracer (concomitant with an inhaled non-radiolabelled dose) and a single oral dose
Trial description: GSK2269557 is being developed as an anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD) and other inflammatory lung diseases such as asthma. This study is designed to investigate the recovery, excretion, and pharmacokinetics (PK) of (14 Carbon [C])-GSK2269557 administered as a single intravenous (IV) dose (concomitant with an inhaled non-radiolabelled dose) and as a single oral dose in 6 healthy male subjects. Subjects will receive [14C] radiolabelled GSK2269557 administered as IV infusion, with a nonradiolabelled dose of GSK2269557 via dry powder inhaler (DPI) in treatment period 1 and a single dose of [14C]-GSK2269557, administered as an oral solution in treatment period 2. There will be a washout period of at least 14 days after inhaled and IV dosing before subjects takes part in treatment period 2. The IV microtracer dose of GSK2269557 will be administered concomitant to an inhaled non-radiolabelled dose to ensure that the pharmacokinetics represent a clinically relevant dose. The total study duration will be up to 11 weeks, including a screening visit, 2 treatment periods and a follow-up visit.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Area under the concentration-time curve (AUC) from time zero (pre-dose) to infinity (0-inf) (AUC [0-inf]) of total radiolabelled drug-related material following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

AUC (0-inf) of total radiolabelled drug-related material following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

AUC from time zero (pre-dose) to last time of quantifiable concentration (0-t) (AUC [0-t]) of total radiolabelled drug-related material following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

AUC [0-t] of total radiolabelled drug-related material following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Maximum observed concentration (Cmax) of total radiolabelled drug-related material following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

Cmax of total radiolabelled drug-related material following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Time to Cmax (tmax) of total radiolabelled drug-related material following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

Tmax of total radiolabelled drug-related material following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Apparent terminal phase half-life (t1/2) of total radiolabelled drug-related material following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

T1/2 of total radiolabelled drug-related material following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Urinary cumulative excretion following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose, 0-6, 6-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours Post-dose

Fecal cumulative excretion following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose, 0-6, 6-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours Post-dose

Urinary cumulative excretion following oral dose of GSK2269557

Timeframe: Pre-dose, 0-6, 6-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours Post-dose

Fecal cumulative excretion following oral dose of GSK2269557

Timeframe: Pre-dose, 0-6, 6-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours Post-dose then every 24 hours up to Day 14

Secondary outcomes:

AUC (0-inf) of parent GSK2269557 and [14C]-GSK22695571 following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

AUC (0-inf) of parent GSK2269557 and [14C]-GSK22695571 following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

AUC (0-t) of parent GSK2269557 and [14C]-GSK22695571 following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

AUC (0-t) of parent GSK2269557 and [14C]-GSK22695571 following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Cmax of parent GSK2269557 and [14C]-GSK22695571 following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

Cmax of parent GSK2269557 and [14C]-GSK22695571 following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Tmax of parent GSK2269557 and [14C]-GSK22695571 following IV dose with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

Tmax of parent GSK2269557 and [14C]-GSK22695571 following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

T1/2 of parent GSK2269557 and [14C]-GSK22695571 following IV with an inhaled concomitant non radiolabelled dose of GSK2269557

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

T1/2 of parent GSK2269557 and [14C]-GSK22695571 following oral dose of GSK2269557

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Volume of distribution of parent [14C]-GSK22695571 after IV dose

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

IV clearance of parent [14C]-GSK22695571 after IV dose

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post dose

Absolute bioavailability of GSK2269557 following inhaled administration

Timeframe: Pre-dose and 0, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 168 hours post-dose

Absolute bioavailability of GSK2269557 following oral administration

Timeframe: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 168 hours post-dose

Number of subjects with adverse events (AEs) and serious AEs (SAEs)

Timeframe: Up to Week 11

Number of subjects having abnormal clinical Chemistry laboratory parameters as a measure of safety

Timeframe: Up to Week 11

Number of subjects having abnormal hematology laboratory parameters as a measure of safety

Timeframe: Up to Week 11

Number of subjects having abnormal values for urinalysis as a measure of safety

Timeframe: Up to Week 11

Number of subjects with abnormal electrocardiogram (ECG) findings

Timeframe: Up to Week 11

Number of subjects with abnormal values for blood pressure (BP)

Timeframe: Up to Week 11

Number of subjects with abnormal values for body temperature

Timeframe: Up to Week 11

Number of subjects with abnormal pulse rate

Timeframe: Up to Week 11

Number of subjects with abnormal respiratory rate

Timeframe: Up to Week 11

Interventions:
  • Drug: [14C]-GSK2269557 IV infusion
  • Drug: GSK2269557 via DPI
  • Drug: [14C]-GSK2269557 oral solution
    • Enrollment:
    6
    Primary completion date:
    2017-22-12
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Andrew W Harrell, Robert Wilson, Yau Lun Man, Kylie Riddell, Emily Jarvis, Graeme Young, Robert Chambers, Lee Crossman, Alex Georgiou, Adrian Pereira, David Kenworthy, Claire Beaumont, Miriam Marotti, Denisa Wilkes, Edith M Hessel, and William A Fahy. An innovative approach to characterize clinical ADME and pharmacokinetics of the inhaled drug nemiralisib using an intravenous microtracer combined with an inhaled dose, and an oral radiolabel dose in healthy male subjects. Drug Metab Dispos. 2019;47(12):1457-1468 DOI: 10.1124/dmd.119.088344 PMID: 31649125
    Medical condition
    Pulmonary Disease, Chronic Obstructive
    Product
    nemiralisib
    Collaborators
    Not applicable
    Study date(s)
    November 2017 to December 2017
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Male
    Age
    30 - 55 years
    Accepts healthy volunteers
    Yes
    • Subject must be 30 to 55 years of age inclusive, at the time of signing the informed consent.
    • Subjects who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring; A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • Alanine aminotransferase (ALT) > 1.5x Upper limit of normal (ULN).
    • Bilirubin > 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subject must be 30 to 55 years of age inclusive, at the time of signing the informed consent.
    • Subjects who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring; A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • A history of regular bowel movements (averaging one or more bowel movements per day).
    • Body weight >= 50 kilograms (Kg) and body mass index (BMI) within the range 19.0–31.0 kg per meter square (kg/m^2) (inclusive).
    • Male subjects will be included.
    • Subjects with female partners of childbearing potential must agree to use contraception during the treatment period, from the time of first dose of study medication until follow-up, and refrain from donating sperm during this period.
    • Capable of giving signed informed consent.
    Exclusion criteria:
    • Alanine aminotransferase (ALT) > 1.5x Upper limit of normal (ULN).
    • Bilirubin > 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
    • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
    • Mean QT duration corrected for heart rate by Fridericia’s formula (QTCF) > 450 milliseconds (msec).
    • Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead ECG.
    • A pre-existing condition(s) interfering with normal gastrointestinal (GI) anatomy or motility, including constipation, malabsorption or other GI dysfunction which may interfere with the absorption, distribution, metabolism or elimination of the study drug. Subjects with a history of cholecystectomy must be excluded.
    • At screening, a supine or semi-supine BP that is persistently higher (triplicate measurements at least 2 minutes apart than 140/90 millimeters of mercury (mmHg).
    • At screening, a supine or semi-supine mean heart rate (HR) outside the range 40-90 beats per minute (BPM).
    • Subject is mentally or legally incapacitated.
    • A history of respiratory disease (example given [e.g.] history of asthma) in the last 10 years.
    • 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) before the first dose of study medication, unless in the opinion of the investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
    • Need of Paracetamol or Acetaminophen, at doses of > 2 grams (g)/day. Other concomitant medication may be considered on a case by case basis by the GSK Medical Monitor.
    • The subject has participated in a clinical trial and has received an investigational product (IP) within 3 months before their first dose in the current study.
    • Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. A subject’s previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study.
    • Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening.
    • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
    • A positive test for Human Immunodeficiency Virus (HIV) antibody.
    • A positive pre-study drug/alcohol screen.
    • Exposure to more than four new chemical entities within 12 months before the subject’s first dose.
    • Subjects have received a total body radiation dose of greater than 5.0 micro sievert (mSv) (upper limit of World Health Organization [WHO] category II) or exposure to significant radiation (e.g. serial x-ray or computed tomography [CT] scans, barium meal etc) in the 12 months before this study.
    • An occupation which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays within the past 12 months.
    • Participation in the study would result in donation of blood or blood products in excess of 500 milliliters (mL) within a 90 day period.
    • Unwillingness or known inability to follow the procedures outlined in the protocol, including the use of the Enterotest capsule.
    • History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of >21 units. One unit is equivalent to 8 g of alcohol: a halfpint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
    • Urinary cotinine levels indicative of smoking; current smoker; or ex-smokers who gave up less than 6 months ago or who have a history of more than 10 pack-years. Pack-years = cigarettes per day x number of years smoked/20

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    London, United Kingdom, NW10 7EW
    Status
    Study Complete
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    Study documents

    Protocol
    Available language(s): English
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    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2017-22-12
    Actual study completion date
    2017-22-12

    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

    Additional information
    Not applicable
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