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Trial record 32 of 272 for:    "Idiopathic pulmonary fibrosis"

Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging

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ClinicalTrials.gov Identifier: NCT03069989
Recruitment Status : Recruiting
First Posted : March 3, 2017
Last Update Posted : June 8, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
GSK3008348 is being developed as a treatment for IPF. A first-time-in-human study showed that single nebulized doses of 1−3000 micrograms (mcg) GSK3008348 in healthy volunteers were well tolerated, with pharmacokinetic (PK) exposures within the defined limits set in the protocol. The proposed study is a 2-cohort study of single doses, intended to evaluate the safety, tolerability and PK of the drug in participants with IPF not currently treated with pirfenidone or nintedanib, and to obtain preliminary information on target engagement. Cohort 1 will be a 2-period, randomized, double-blind, placebo-controlled group with at least 7 days washout between doses, and follow-up period of up to 7-14 days. Cohort 2 is optional. It will be designed to further explore safety and to provide additional information on the target engagement profile of GSK3008348. The total duration of the study will be up to 62 days.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: GSK3008348 Drug: Placebo Drug: [18F]-FBA-A20FMDV2 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Study of Single Doses to Evaluate the Safety, Tolerability, Pharmacokinetics and Target Engagement of Nebulised GSK3008348 in Idiopathic Pulmonary Fibrosis Patients, Using Positron Emission Tomography (PET) Imaging
Actual Study Start Date : June 13, 2017
Estimated Primary Completion Date : May 9, 2019
Estimated Study Completion Date : May 9, 2019


Arm Intervention/treatment
Experimental: Cohort 1 GSK3008348
Participants will receive a single nebulized dose of GSK3008348 during each of 2 planned dosing periods and up to 3 microdose administrations of [18F]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: GSK3008348
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Placebo Comparator: Cohort 1 Placebo
Participants will receive a single nebulized dose of placebo during each of 2 planned dosing periods and up to 3 microdose of [18F]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: Placebo
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Experimental: Cohort 2 GSK3008348
Participants will receive a single nebulized dose of GSK3008348 during each of 2 planned dosing periods and up to 3 microdose administrations of [18F]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: GSK3008348
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Placebo Comparator: Cohort 2 Placebo
Participants will receive a single nebulized dose of placebo during each of 2 planned dosing periods and up to 3 microdose of [18F]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: Placebo
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.




Primary Outcome Measures :
  1. Volume of distribution (VT) (not corrected for air volume) at approximately 30 minutes (min) post-dose compared to pre-dose measured by PET [ Time Frame: Pre-dose and 30 min ]
    Changes in the uptake of [18F]-fluorobenzoic acid (FBA)-A20FMDV2 (radio-labeled specific ligand) in the whole lung assessed as VT will be used to evaluate target engagement in the lung after single nebulized doses of GSK3008348.

  2. Number of subjects with any adverse event (AE) and any serious adverse event (SAE) [ Time Frame: Up to 42 days ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function.

  3. Systolic and diastolic blood pressure (BP) as a measure of safety [ Time Frame: Up to 72 days ]
    Blood pressure will be measured in a semi-supine position after 5 min rest at: pre-dose, and 30 min, 2, 4, 8 and 24 hours (hrs) post-dose in dosing period 1; pre-dose, post-PET scan, on leaving the unit on Day 1, and at pre-PET scan on Day 2 in dosing period 2; and at follow-up.

  4. Heart rate (HR) as a measure of safety [ Time Frame: Up to 72 days ]
    Heart rate will be measured in a semi-supine position after 5 min rest at: pre-dose, and 30 min, 2, 4, 8 and 24 hrs post-dose in dosing period 1; pre-dose, post-PET scan, on leaving the unit on Day 1, and at pre-PET scan on Day 2 in dosing period 2; and at follow-up.

  5. Body temperature as a measure of safety [ Time Frame: Up to 72 days ]
    Body temperature will be measured in a semi-supine position after 5 min rest at: pre-dose, and 30 min, 2, 4, 8 and 24 hrs post-dose in dosing period 1; pre-dose, post-PET scan, on leaving the unit on Day 1, and at pre-PET scan on Day 2 in dosing period 2; and at follow-up.

  6. Respiratory rate as a measure of safety [ Time Frame: Up to 72 days ]
    Respiratory rate will be measured in a semi-supine position after 5 min rest at: pre-dose, and 30 min, 2, 4, 8 and 24 hrs post-dose in dosing period 1; pre-dose, post-PET scan, on leaving the unit on Day 1, and at pre-PET scan on Day 2 in dosing period 2; and at follow-up.

  7. 12-lead electrocardiogram (ECG) as a measure of safety [ Time Frame: Up to 72 days ]
    ECG will be performed at 30 min, 2, 4, 8 hrs post-dose on Day 1 and at 24 hrs post dose in dosing period 2.

  8. Number of subjects with abnormal hematology parameters [ Time Frame: Up to 72 days ]
    Hematology parameters included platelet count, red blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, white blood cell count, and neutrophil, lymphocyte, monocyte, eosinophil and basophil differential.

  9. Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to 72 days ]
    Clinical chemistry parameters included blood urea nitrogen, creatinine, glucose non-fasting, aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyl transferase, potassium, sodium, calcium, total and direct bilirubin, creatine phosphokinase, total protein and albumin.

  10. Number of subjects with abnormal urinalysis parameters [ Time Frame: Up to 72 days ]
    Urinalysis parameters included Specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick. (Microscopy, culture and sensitivity analysis if required).

  11. Forced expiratory volume in 1 second (FEV1) [ Time Frame: Up to 72 days ]
    FEV1 will be measured at screening, and pre-dose, 1 and 24 hrs post-dose in dosing period 1, pre-dose in dosing period 2, and at follow-up.

  12. Forced vital capacity (FVC) [ Time Frame: Up to 72 days ]
    FVC will be measured at screening, and pre-dose, 1 and 24 hrs post-dose in dosing period 1, pre-dose in dosing period 2, and at follow-up.

  13. Diffusing capacity of the lungs for carbon monoxide (DLCO) [ Time Frame: 24 hrs post-dose in period 1. ]
    DLCO will be measured at screening, pre-dose and 24 h post-dose in dosing period 1.


Secondary Outcome Measures :
  1. Area under the plasma concentration-time curve from zero (0) hrs to time (t) [AUC(0-t)] of GSK3008348 [ Time Frame: Period 1: at pre-dose, 15 and 30 min, 1, 2, 4, 8, 12, 18 and 24 hrs after the start of nebulization, Period 2: at pre-dose, 15 and 30 min, 2 and 4 hrs post-dose on Day 1, and on arrival and discharge from imaging unit on Day 2. ]
    Blood samples will be collected at indicated time points and concentration of GSK3008348 will be determined

  2. Area under the plasma concentration-time curve from zero (0) hrs to infinity (inf) AUC [(0-inf)] [ Time Frame: Period 1: at pre-dose, 15 and 30 min, 1, 2, 4, 8, 12, 18 and 24 hrs after the start of nebulization, Period 2: at pre-dose, 15 and 30 min, 2 and 4 hrs post-dose on Day 1, and on arrival and discharge from imaging unit on Day 2. ]
    Blood samples will be collected at indicated time points and concentration of GSK3008348 will be determined

  3. Maximum observed plasma drug concentration (Cmax) of GSK3008348 [ Time Frame: Period 1: at pre-dose, 15 and 30 min, 1, 2, 4, 8, 12, 18 and 24 hrs after the start of nebulization, Period 2: at pre-dose, 15 and 30 min, 2 and 4 hrs post-dose on Day 1, and on arrival and discharge from imaging unit on Day 2. ]
    Blood samples will be collected at indicated time points and concentration of GSK3008348 will be determined

  4. Time to maximum observed plasma drug concentration (Tmax) of GSK3008348 [ Time Frame: Period 1: at pre-dose, 15 and 30 min, 1, 2, 4, 8, 12, 18 and 24 hrs after the start of nebulization, Period 2: at pre-dose, 15 and 30 min, 2 and 4 hrs post-dose on Day 1, and on arrival and discharge from imaging unit on Day 2. ]
    Blood samples will be collected at indicated time points and concentration of GSK3008348 will be determined

  5. Terminal half-life (T1/2) of GSK3008348 [ Time Frame: Period 1: at pre-dose, 15 and 30 min, 1, 2, 4, 8, 12, 18 and 24 hrs after the start of nebulization, Period 2: at pre-dose, 15 and 30 min, 2 and 4 hrs post-dose on Day 1, and on arrival and discharge from imaging unit on Day 2. ]
    Blood samples will be collected at indicated time points and concentration of GSK3008348 will be determined

  6. VT at up to 28 hrs post-dose compared to pre-dose measured by PET [ Time Frame: 28 hrs post-dose ]
    Changes in the uptake of [18F]-FBA-A20FMDV2 in the whole lung assessed as VT to evaluate duration of target engagement.



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male participants aged >= 50 years, and female participants aged >=55 years, at the time of signing the informed consent.
  • Diagnosis of definite or probable IPF as determined by a responsible and experienced chest physician and based on established criteria defined by the American Thoracic Society/European Respiratory Society Internationale Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias.
  • Ambulant and capable of attending outpatient visits.
  • FVC > 50 percent predicted and DLCO > 40 percent predicted.
  • Body weight >= 45 kilograms (kg) and body mass index (BMI) within the range 18.0-35.0 kg/square meter (inclusive).
  • Male and female
  • Male participants: A male participant must agree to use contraception as detailed in this protocol during the study and for at least 90 days after the follow up visit, and refrain from donating sperm during this period.
  • Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) as defined in the protocol.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

  • ALT and bilirubin > 1.5x upper limit of normal (ULN; isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • QT corrected (QTc) > 450 milliseconds (msec), or QTc > 480 msec in participants with Bundle Branch Block.
  • Current IPF exacerbation, or upper or lower respiratory tract infection on admission to the clinical unit.
  • History of or suffers from claustrophobia, or unable to lie flat and still on their back for up to 2 hrs in the PET scanner.
  • Extent of emphysema greater than the extent of fibrotic change on High-Resolution Computed Tomography (HRCT) scan, based on investigator judgment.
  • FEV1/FVC ratio < 0.70 at screening (post-bronchodilator).
  • History of sensitivity to the study treatment, or components thereof, or a history of drug or other allergy that, in the opinion of the investigators or Medical Monitor, contraindicates their participation.
  • Any current oro-pharygneal disease or disorders as judged by the investigator.
  • Currently taking pirfenidone or nintedanib, or received pirfenidone or nintedanib within 30 days of the first dose of study treatment.
  • Taken, within 7 days or 5 half-lives (whichever is longer) before the first dose of study treatment, organic anion transporter (OAT) substrates with a narrow therapeutic index (example: methotrexate and tenofovir), vitamins, or dietary or herbal supplements, unless in the opinion of the investigator and sponsor the supplement will not interfere with the study medication.
  • Long-term continuous home oxygen therapy (use of oxygen that is only intermittent and for symptom relief is acceptable).
  • Participation in a clinical trial and receipt of an investigational medicinal product within the following time period before the first dose 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 4 new investigational medicinal products within 12 months before the first dose.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening, or positive Hepatitis C antibody test result at screening or within 3 months before the first dose of study treatment.

Note: participants with a positive Hepatitis C antibody test because of previous, resolved disease can be enrolled if a confirmatory negative Hepatitis C Ribonucleic Acid (RNA) test is obtained.

  • Previous or current exposure to animals that may harbour Food and Mouth Disease Virus (FMDV2).
  • Previous long term (>= 3 months) residence in a country where FMDV2 is endemic (such as certain areas of Africa, Asia and South America.
  • Where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days.
  • History of drug or alcohol abuse that in the opinion of the investigator affects their participation in the study.
  • Exposure to ionizing radiation in excess of 10 Millisievert (mSv) above background over the previous 3 year period as a result of occupational exposure or previous participation in research studies. Clinically justified (therapeutic or diagnostic) exposures are not included in the exposure calculation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03069989


Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United Kingdom
GSK Investigational Site Terminated
London, United Kingdom, SE1 9RT
GSK Investigational Site Recruiting
London, United Kingdom, SW3 6HP
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
London, United Kingdom, WC1E 6JF
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
London, United Kingdom
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03069989     History of Changes
Other Study ID Numbers: 204715
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Tolerability
IPF
PET imaging
Idiopathic Pulmonary Fibrosis
Safety
Pharmacokinetics
Double-blind

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial