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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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ClinicalTrials.gov |
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Last refreshed on:
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12 December 2020 |
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Main ID: |
NCT03069989 |
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Date of registration:
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28/02/2017 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging
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Scientific title:
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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 |
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Date of first enrolment:
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June 13, 2017 |
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Target sample size:
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8 |
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Recruitment status: |
Terminated |
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URL:
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https://clinicaltrials.gov/show/NCT03069989 |
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Study type:
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Interventional |
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Study design:
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Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
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Phase:
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Phase 1
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Countries of recruitment
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United Kingdom
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Contacts
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Name:
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GSK Clinical Trials |
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Address:
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Telephone:
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Email:
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Affiliation:
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GlaxoSmithKline |
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Key inclusion & exclusion criteria
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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.
Age minimum:
50 Years
Age maximum:
N/A
Gender:
All
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Health Condition(s) or Problem(s) studied
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Idiopathic Pulmonary Fibrosis
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Intervention(s)
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Drug: [18F]-FBA-A20FMDV2
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Drug: Placebo
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Drug: GSK3008348
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Primary Outcome(s)
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Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
[Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose]
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Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters
[Time Frame: Pre-dose (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose]
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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
[Time Frame: Up to 62 days]
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Period 2: Change From Baseline in Hematology Parameter: Hematocrit
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Hematology Parameter: Hemoglobin
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Vital Sign: Temperature
[Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Vital Signs: DBP and SBP
[Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)]
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Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
[Time Frame: Baseline (Day -1), 1 hour and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Vital Sign: Respiration Rate
[Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)]
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Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Vital Signs: Heart Rate
[Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)]
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Period 1: Change From Baseline in Hematology Parameter: Hematocrit
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 1: Change From Baseline in Vital Signs: Heart Rate
[Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose]
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Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick
[Time Frame: Baseline (Day -1), 24 hours post-GSK3008348 dose and Day 15 (follow-up)]
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Period 2: Change From Baseline in Hematology Parameter: Hemoglobin
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters
[Time Frame: Pre-dose (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge), Day 2 (pre-PET scan) and Day 15 (follow-up)]
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Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose
[Time Frame: Baseline (pre-dose) and 30 minutes post-dose]
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Period 1: Change From Baseline in Vital Sign: Respiration Rate
[Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
[Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose]
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Period 2: Change From Baseline in Vital Sign: Temperature
[Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)]
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Secondary Outcome(s)
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Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose
[Time Frame: Baseline (pre-dose) and 24 hours post-dose PET scan 2]
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Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Time (AUC[0-t]) After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose]
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Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose]
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Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose]
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Period 2: AUC(0-t) After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose]
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Period 2: Cmax After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose]
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Period 2: Tmax After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose]
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Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose]
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Period 2: t1/2 After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose]
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Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose]
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Period 2: AUC(0-infinity) After Single Dose Administration of GSK3008348
[Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose]
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Secondary ID(s)
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2016-003674-41
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204715
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Source(s) of Monetary Support
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Please refer to primary and secondary sponsors
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