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CompletedNCT02663089Updated Oct 6, 2021

A Phase 1 (Ph1), Single Dose (SD), GSK961081 Absorption, Distribution, Metabolism, and Excretion (ADME) Study in Healthy Subjects

A Phase 1 interventional study of [14C]-GSK961081 solution for IV infusion and [14C]-GSK961081 oral solution in Pulmonary Disease, Chronic Obstructive, sponsored by Theravance Biopharma. Completed at 1 site in United Kingdom. Open to male participants aged 30 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-10-06.

Sponsored by Theravance Biopharma · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
6
Allocation
Not applicable
Ages
30 Years to 55 Years
Sex
Male
01

Study summary

Batefenterol (GSK961081) is a bifunctional bronchodilator that is being developed for the treatment of Chronic Obstructive Pulmonary Disease (COPD). Absorption, metabolism and excretion of batefenterol have been studied in animals, in vitro, and in previous clinical studies; however, the elimination routes and metabolic pathways of batefenterol have not been fully elucidated in humans. This is an open-label, single centre, non-randomised, 2-period single-sequence crossover, mass balance study to determine total radioactivity (drug related material) in plasma, the rate and extent of excretion of total radioactivity in urine and faeces and the total recovery of radioactivity of [14C] GSK961081 administered as a single IV dose (concomitant with an inhaled non-radiolabelled dose) and a single oral dose, in healthy male subjects. A total of 6 healthy male subjects will be enrolled. The duration of each subject in the study is up to 11 weeks, which consists of a screening visit, 2 Treatment Periods, and a follow up visit.

02

Conditions studied

  • Pulmonary Disease, Chronic Obstructive

Keywords

  • total radioactivity
  • [14C]-GSK961081
  • Pharmacokinetics
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Microtracer
03

In context

Lung Diseases

3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.

This study's enrollment of 6 is below the median of 72 across 2,118 interventional studies indexed under Lung Diseases.

Browse Lung Diseases studies →

Lead sponsor

Theravance Biopharma is the lead sponsor of 47 studies on the registry; none are open to participants now.

Of its 24 completed or terminated interventional studies of FDA-regulated products, 11 (46%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 55 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  • Between 30 and 55 years of age inclusive, at the time of signing the informed consent.
  • 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/square metre (m\^2) (inclusive)
  • Sex: Male
  • Subjects with female partners of child bearing potential must use a condom from the time of first dose of study medication until follow-up.
  • Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion criteria

Exclusion Criteria:

  • Alanine aminotransferase (ALT) and bilirubin >1.5xupper limit of normal (ULN) (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 corrected QT interval (QTc) > 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 blood pressure (BP) that is persistently higher (triplicate measurements at least 2 min apart) than 140/90 millimetres of mercury (mmHg).
  • At screening, a supine mean HR outside the range 40-90 beats per minute (BPM).
  • Subject is mentally or legally incapacitated.
  • A history of respiratory disease (e.g. history of asthmatic symptoms) 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.
  • 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 grams (g) of alcohol: a half-pint (approximately 240 millilitres [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 multiplied by number of years smoked then divided by 20.
  • History of sensitivity to any of the study medications or its components, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates the subject's participation.
  • Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months before the first dose of study treatment.
  • A positive test for Human Immunodeficiency Virus (HIV) antibody
  • A positive pre-study drug/alcohol screen.
  • 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.
  • Exposure to more than four new chemical entities within 12 months before the subject's first dose.
  • Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. A subjects' previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study.
  • Subjects who have received a total body radiation dose of greater than 5.0 millisievert (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.
  • Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days before the first dose of study medication until the follow-up visit.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol, including the use of the enterotest capsule.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
6 participants (actual)

Study arms

  • Experimental
    [14C]-GSK961081 IV+GSK961081 inhalation; [14C]-GSK961081 oral

    On Day 1 of Treatment Period 1, after an overnight fast of at least 8 hours, each subject will receive \[14C\] GSK961081 4 micrograms (mcg) by IV infusion over 1 hour. Within 5 minutes after the start of infusion, subjects will take 1200 mcg non-radiolabelled GSK961081 by inhalation. After Treatment Period 1, there will be a washout of at least 2 weeks. On Day 1 of Treatment Period 2, after an overnight fast of at least 8 hours, each subject will take 200 mcg \[14C\]-GSK961081 as an oral solution.

    Drug: [14C]-GSK961081 solution for IV infusion · Drug: [14C]-GSK961081 oral solution · Drug: GSK961081 dry powder for inhalation

Interventions

  • Drug[14C]-GSK961081 solution for IV infusion

    Subjects will receive 10 mL of solution equivalent to 4 mcg of \[14C\]-GSK961081 (approximately 6.2 kilobecquerel \[kBq\]) intravenously as a single dose over 1 hour.

  • Drug[14C]-GSK961081 oral solution

    Subjects will receive 10 mL of solution equivalent to 200 mcg of \[14C\]-GSK961081 (approximately 311 kBq) orally as a single dose with up to 250 mL of water.

  • DrugGSK961081 dry powder for inhalation

    Subjects will receive single dose of 4 actuations of 300 mcg GSK961081 per actuation (1200 mcg GSK961081 total) as inhalation immediately after the start of infusion.

06

What researchers measure

Primary outcomes

  1. AUC(0 inf) of total drug-related material (radioactivity) in plasma after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose) and a single oral dose of [14C] GSK961081

    The following PK parameter will be measured: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0 inf\])

    Time frame: Pre-dose and at 0.25 , 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  2. AUC(0-t) of total drug-related material (radioactivity) in plasma after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose) and a single oral dose of [14C] GSK961081

    The following PK parameter will be measured: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC\[0-t\]).

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  3. Cmax of total drug-related material (radioactivity) in plasma after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose) and a single oral dose of [14C] GSK961081

    The following PK parameter will be measured: maximum observed plasma concentration (Cmax)

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  4. Tmax of total drug-related material (radioactivity) in plasma after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose) and a single oral dose of [14C] GSK961081

    The following PK parameter will be measured: time of occurrence of Cmax (Tmax)

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  5. T1/2 of total drug-related material (radioactivity) in plasma after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose) and a single oral dose of [14C] GSK961081

    The following PK parameter will be measured: terminal phase half-life (t1/2)

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  6. Volume of total radioactivity (drug related material) after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose)

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  7. Clearance of total radioactivity (drug related material) after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose)

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  8. Urinary and faecal cumulative excretion as a percentage of the total radioactive dose administered over time after a single IV microtracer of [14C] GSK961081 (concomitant with an inhaled non-radiolabelled dose) and a single oral dose of [14C] GSK961081

    Time frame: Pre-dose and at 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours post-dose during Treatment Period 1 and 2

Secondary outcomes

  1. AUC(0-inf) of parent GSK961081 and [14C] GSK961081 in plasma after a single IV microtracer of [14C]-GSK961081 concomitant with an inhaled non-radiolabelled GSK961081 dose and a single oral dose of [14C] GSK961081

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  2. AUC(0-t) of parent GSK961081 and [14C] GSK961081 in plasma after a single IV microtracer of [14C]-GSK961081 concomitant with an inhaled non-radiolabelled GSK961081 dose and a single oral dose of [14C] GSK961081

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  3. Cmax of parent GSK961081 and [14C] GSK961081 in plasma after a single IV microtracer of [14C]-GSK961081 concomitant with an inhaled non-radiolabelled GSK961081 dose and a single oral dose of [14C] GSK961081

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  4. Tmax of parent GSK961081 and [14C] GSK961081 in plasma after a single IV microtracer of [14C]-GSK961081 concomitant with an inhaled non-radiolabelled GSK961081 dose and a single oral dose of [14C] GSK961081

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  5. T1/2 of parent GSK961081 and [14C] GSK961081 in plasma after a single IV microtracer of [14C]-GSK961081 concomitant with an inhaled non-radiolabelled GSK961081 dose and a single oral dose of [14C] GSK961081

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  6. Volume of parent GSK961081 and [14C] GSK961081 after a single IV microtracer of [14C]-GSK961081 concomitant with an inhaled non-radiolabelled GSK961081 dose

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  7. Clearance of parent GSK961081 and [14C] GSK961081 after a single IV microtracer of [14C]-GSK961081 concomitant with an inhaled non-radiolabelled GSK961081 dose

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  8. Oral and inhaled absolute bioavailability (F)

    Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 hours post-dose during Treatment Period 1 and 2

  9. Number of subjects with any adverse events (AEs) as a measure of safety

    An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

    Time frame: Up to 7 weeks

  10. Composite of Hematology parameters as a measure of safety

    The following hematology parameters will be measured: Platelet Count, red blood cell (RBC) count, Hemoglobin, Hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC) count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils

    Time frame: Up to 11 weeks

  11. Composite of Clinical Chemistry parameters as a measure of safety

    The following clinical chemistry parameters will be measured: Urea, Creatinine, Glucose (fasting), Uric acid, Potassium, Sodium, Calcium, Chloride, phosphate, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase, Gamma-glutamyl transferase (GGT), Cholesterol, Triglycerides, Total Bilirubin, Total Protein, Albumin, and Globulin.

    Time frame: Up to 11 weeks

  12. Composite of Urinalysis parameters as a measure of safety

    The following urinalysis parameters will be measured by dip stick method: Protein, Blood, Ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites, power of hydrogen (pH). If urine dipstick is abnormal for leukocyte esterase, nitrites, blood or protein, microscopic examination will be performed.

    Time frame: Up to 11 weeks

  13. Electrocardiogram (ECG) as a measure of safety

    12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT using Bazett's formula (QTcB) or corrected QT using Fridericia's formula (QTcF) intervals.

    Time frame: Up to 11 weeks

  14. Temperature as a measure of safety

    Time frame: Up to 11 weeks

  15. Systolic and diastolic blood pressure as a measure of safety

    Time frame: Up to 11 weeks

  16. Pulse rate as a measure of safety

    Time frame: Up to 11 weeks

  17. Respiratory rate as a measure of safety

    Time frame: Up to 11 weeks

07

Study locations

1 site
  • GSK Investigational Site
    London, NW10 7EW, United Kingdom
08

References and documents

Publications

  • Ambery C, Young G, Fuller T, Lazaar AL, Pereira A, Hughes A, Ramsay D, van den Berg F, Daley-Yates P. Pharmacokinetics, Excretion, and Mass Balance of [14 C]-Batefenterol Following a Single Microtracer Intravenous Dose (Concomitant to an Inhaled Dose) or Oral Dose of Batefenterol in Healthy Men. Clin Pharmacol Drug Dev. 2018 Nov;7(8):901-910. doi: 10.1002/cpdd.616. Epub 2018 Sep 19. Erratum In: Clin Pharmacol Drug Dev. 2019 Oct;8(7):971. doi: 10.1002/cpdd.719. PubMed 30230263 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 6, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02663089
Lead sponsor
Theravance Biopharma
Collaborators
Hammersmith Medicines Research, GlaxoSmithKline
Responsible party
Sponsor
First posted
Jan 26, 2016
Start date
Feb 8, 2016
Primary completion
Mar 17, 2016
Completion
Mar 17, 2016
Last update
Oct 6, 2021

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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