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Phase 1 Completed N=6 Treatment

Absorption & Elimination of Radiolabelled GSK2269557

Pulmonary Disease, Chronic Obstructive
Source: ClinicalTrials.gov NCT03315559 ↗
Enrolled (actual)
6
Serious AEs
0.0%
Results posted
Mar 2019
Primary outcomePrimary: Area Under Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Infinite Time (0 to Inf) and AUC From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 — 812.8550; 770.3316 Hour*picogram Equivalent per millilitre

Summary

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Area Under Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Infinite Time (0 to Inf) and AUC From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
812.8550; 770.3316
PRIMARY
AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (0 to Inf) and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
34749.40; 31730.13
PRIMARY
Maximum Observed Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
204.4057
PRIMARY
Cmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
703.5192
PRIMARY
Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
0.2333
PRIMARY
Tmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
7.0000
PRIMARY
Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
56.9152
PRIMARY
Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
39.6279
PRIMARY
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
0.3961; 2.1998; 18.1265; 28.0481; 33.7465; 45.2398
PRIMARY
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
3.81330; 14.6367; 40.9583; 48.8217; 60.7617; 64.1667
SECONDARY
AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
33374.56; 28425.82; 750.5798; 546.4731
SECONDARY
AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2
25107.96; 16913.06
SECONDARY
Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
5258.98; 205.6264
SECONDARY
Cmax of [14C]-GSK2269557 in Plasma for Treatment Period 2
398.8822
SECONDARY
Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
0.0333; 0.2333
SECONDARY
Tmax of [14C]-GSK2269557 in Plasma for Treatment Period 2
6.0000
SECONDARY
t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
58.4408; 54.7223
SECONDARY
t1/2 of [14C]-GSK2269557 in Plasma for Treatment Period 2
50.8028
SECONDARY
Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma
727.7102; 851.4423
SECONDARY
Clearance of Parent [14C]-GSK2269557 After IV Dose Only in Plasma
10.7849
SECONDARY
Inhaled Absolute Bioavailability (F) for Treatment Period 1
0.3807; 0.4213
SECONDARY
Oral Absolute Bioavailability (F) for Treatment Period 2
0.3515; 0.3261
SECONDARY
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
0; 1; 0; 0
SECONDARY
Number of Participants With Hematology Parameters of Potential Clinical Concern
2; 1
SECONDARY
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern
0; 0
SECONDARY
Number of Participants With Clinically Significant Urinalysis Findings
0; 0
SECONDARY
Number of Participants With Electrocardiogram Findings of Clinical Significance
0; 0
SECONDARY
Number of Participants With Vital Signs of Potential Clinical Concern
1; 0; 1; 0

Eligibility 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 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 siever
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03315559). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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