Acute Lung InjuryPhase 1NCT03328117
A Study to Investigate the Effects of Imatinib on Pulmonary Vascular Dysfunction in a Human Model of Lung Injury
A Phase 1 study testing Imatinib in people with Acute Lung Injury, run by Exvastat Ltd. at 1 site in United Kingdom.
Trial summary
The study is a randomized, double-blind, placebo-controlled clinical study of imatinib (as mesilate) in healthy subjects exposed inhaled lipopolysaccharide. During the study, eight oral doses of imatinib, or placebo, will each be taken 12 hours apart, before subjects are exposed to nebulized lipopolysaccharide (LPS). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Lung Injury
- What is being tested?
- Imatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Nov 2017to 5 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Are able and willing to provide written informed consent to participate in this clinical study.
- Healthy males and females, between 18 and 55 years old (both inclusive) at the screening visit.
- Male subjects must practice an acceptable contraceptive method from the time of first IMP administration until 6 weeks after the follow-up visit.
- Female subjects must either be:
- Of non-childbearing potential:
- Or if of childbearing potential, must practice an acceptable contraceptive method from 4 weeks before the first IMP administration until 6 weeks after the follow-up visit.
Show all 13Show fewer
- Good general health as ascertained by detailed medical history and physical examination at the screening visit.
- Body mass index ≥18.0 and ≤30 kg/m2 at the screening visit.
- No clinically relevant abnormalities in the 12-lead ECG as per the Investigator's judgement at the screening visit
- No clinically relevant abnormalities in results of clinical laboratory tests as per the Investigator's judgement at the screening visit.
- Normal spirometry (FEV1 ≥ 85% of predicted, FEV1/FVC ratio ≥ 70%) at the screening visit.
- Non-smokers or no history of smoking (including e-cigarettes and other forms of vaporizing/inhalation) in the last 6 months prior to the screening visit.
- Subjects must be able to communicate well with the Investigator/designee.
Who cannot join
- History of hypersensitivity to the IMP or any of the excipients or to medicinal products with similar chemical structures.
- Presence of any clinically relevant acute or chronic disease which could interfere with the subject safety during the study, expose the subject to undue risk, limit the biological sampling, interfere with the absorption of the investigational product (or interfere with the study objectives.
- Any history of previous respiratory, hematological or malignant disease, including childhood asthma.
- Any history of chronic renal, cardiac (previous myocardial infarction, diagnosis of cardiac failure or cardiac rhythm disturbances such as atrial fibrillation) or hepatic impairment.
- Current evidence of ongoing or acute infection, history of repeated or chronic significant infections, or history of serious infection within 3 months of randomization. Acute infection is defined as a history of febrile illness (> 38°C), or 2 or more of the following symptoms within the last 7 days prior to the screening visit or Day 1: cough, sore throat, runny nose, sneezing, limb/joint pain, headache or vomiting/diarrhea.
- Any condition that in the opinion of the Investigator will require regular concomitant medication including herbal products, or predicted need of any concomitant medication during the study.
Show all 22Show fewer
- Intake of any prescription and over-the-counter medication (except paracetamol, hormonal contraceptives and hormonal replacement therapy) including herbal and dietary supplements (including St John's Wort), vitamins and minerals, within 7 days or 5 half-lives (whichever is longer) prior to the first dose of IMP.
- Systolic blood pressure < 90 mmHg or > 140 mmHg, or diastolic blood pressure < 50 mmHg or > 90 mmHg after 5 minutes in the supine position at the screening visit.
- Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or human immunodeficiency virus (HIV)-1 and/or -2 antibodies at the screening visit.
- Excessive use of caffeine-containing beverages exceeding 500 mg caffeine/day (5 cups of coffee) or intake of food or drinks containing xantine (e.g., caffeine) within 24 hours prior to the screening visit or Day 1.
- Positive urine cotinine test at the screening visit or Day 1, or the inability to stop using nicotine-containing products during the clinical study.
- History or presence of drug addiction (positive urine drug screen at the screening visit or Day 1).
- History of regular alcohol consumption within 6 months of the screening visit defined as an average weekly intake of > 21 units (or an average daily intake of > 3 units) for males or an average weekly intake of > 14 units (or an average daily intake > 2 units) for females.
- Positive urine alcohol test at the screening visit or Day 1, or the inability to refrain from the use of alcohol during the clinical study.
- Intake of any food or any drinks containing grapefruit, Chinese grapefruit (pomelo), Seville orange (including marmalade) or quinine-containing products (e.g., tonic water, bitter lemon) from 7 days prior to Day 1.
- Blood component or plasma donation within 3 months prior to the first dose of IMP.
- Participation in another study with an experimental drug within 3 months before the first dose of IMP. Exclusion period starts from last IMP dosed in previous study to first dose of IMP.
- Any psychological, emotional problems, any disorders or resultant therapy that is likely to invalidate informed consent, or limited the ability of the subject to comply with the protocol requirements.
- Subject is mentally or legally incapacitated.
- A pregnant woman or a nursing mother.
- Unlikely to comply with the protocol requirements, instructions and study-related restrictions; e.g., uncooperative attitude and improbability of completing the clinical study.
- Subjects who, in the opinion of the Investigator, are considered unsuitable for any other reason.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Placebo-controlled, Double-blind Study to Investigate the Effects of the Tyrosine Kinase Inhibitor Imatinib on Pulmonary Vascular Dysfunction in a Human Experimental Model of Acute Lung Injury
The study is a randomized, double-blind, placebo-controlled clinical study of imatinib (as mesilate) in healthy subjects exposed inhaled lipopolysaccharide. During the study, eight oral doses of imatinib, or placebo, will each be taken 12 hours apart, before subjects are exposed to nebulized lipopolysaccharide (LPS). Four hours after LPS exposure, a bronchoalveolar lavage (BAL) will be undertaken, and BAL fluid (BALF collected. Once study assessments are completed, a follow-up visit will be conducted approximately 7 days after the last dose of imatinib.
The primary objective of the study is to investigate the effect of imatinib on LPS-induced pulmonary vascular dysfunction. The primary endpoints of this study are:
- Change in the number of neutrophils in BALF 6 hours after the LPS challenge in subjects exposed to imatinib compared with placebo.
- Change in concentration of total protein in BALF 6 hours after the LPS challenge in subjects exposed to imatinib compared with placebo
- Conditions
- Acute Lung Injury
- Being tested
- Imatinib, Placebo oral capsule
- Medical subject headings
- Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImatinibDrug
Over-encapsulated 100 mg imatinib mesilate tablets
Placebo oral capsuleDrug
Matching placebo oral capsule
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Not described Receives: Drug: Imatinib |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the number of neutrophils in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Change in the number of neutrophils in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Measured: 6 hours after lipopolysaccharide inhalation
Change in concentration of total protein in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Change in concentration of total protein in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Measured: 6 hours after the LPS challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2017
- Study start13 Nov 2017
- Primary completion5 Mar 2018
- Study completion5 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lung InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exvastat Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Muna Albayaty, MBBCh, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03328117
- Sponsor's protocol ID
- EXV001
- Other IDs
- 2017-002203-10, 2017
- Status last verified
- Jul 2018
- First submitted
- 24 Oct 2017
- Last updated
- 13 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-blind Study to Investigate the Effects of the Tyrosine Kinase Inhibitor Imatinib on Pulmonary Vascular Dysfunction in a Human Experimental Model of Acute Lung Injury
- ClinicalTrials.gov ID
- NCT03328117
- Acronym / sponsor ID
- EXV001
- Conditions
- Acute Lung Injury
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Exvastat Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 13 Nov 2017 (actual)
- Primary completion
- 5 Mar 2018 (actual)
- Study completion
- 5 Mar 2018 (actual)
- First posted
- 1 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a randomized, double-blind, placebo-controlled clinical study of imatinib (as mesilate) in healthy subjects exposed inhaled lipopolysaccharide. During the study, eight oral doses of imatinib, or placebo, will each be taken 12 hours apart, before subjects are exposed to nebulized lipopolysaccharide (LPS). Four hours after LPS exposure, a bronchoalveolar lavage (BAL) will be undertaken, and BAL fluid (BALF collected. Once study assessments are completed, a follow-up visit will be conducted approximately 7 days after the last dose of imatinib.
The primary objective of the study is to investigate the effect of imatinib on LPS-induced pulmonary vascular dysfunction. The primary endpoints of this study are:
- Change in the number of neutrophils in BALF 6 hours after the LPS challenge in subjects exposed to imatinib compared with placebo.
- Change in concentration of total protein in BALF 6 hours after the LPS challenge in subjects exposed to imatinib compared with placebo
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Drug: Imatinib |
| Placebo | Placebo comparator | Drug: Placebo oral capsule |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Are able and willing to provide written informed consent to participate in this clinical study.
- Healthy males and females, between 18 and 55 years old (both inclusive) at the screening visit.
- Male subjects must practice an acceptable contraceptive method from the time of first IMP administration until 6 weeks after the follow-up visit.
- Female subjects must either be:
- Good general health as ascertained by detailed medical history and physical examination at the screening visit.
Key exclusion criteria (22 listed)
- History of hypersensitivity to the IMP or any of the excipients or to medicinal products with similar chemical structures.
- Presence of any clinically relevant acute or chronic disease which could interfere with the subject safety during the study, expose the subject to undue risk, limit the biological sampling, interfere with the absorption of the investigational product (or interfere with the study objectives.
- Any history of previous respiratory, hematological or malignant disease, including childhood asthma.
- Any history of chronic renal, cardiac (previous myocardial infarction, diagnosis of cardiac failure or cardiac rhythm disturbances such as atrial fibrillation) or hepatic impairment.
- Current evidence of ongoing or acute infection, history of repeated or chronic significant infections, or history of serious infection within 3 months of randomization. Acute infection is defined as a history of febrile illness (> 38°C), or 2 or more of the following symptoms within the last 7 days prior to the screening visit or Day 1: cough, sore throat, runny nose, sneezing, limb/joint pain, headache or vomiting/diarrhea.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImatinibOver-encapsulated 100 mg imatinib mesilate tablets | Drug | Intervention |
| Placebo oral capsuleMatching placebo oral capsule | Drug | Placebo |
Primary outcome
Change in the number of neutrophils in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Time frame: 6 hours after lipopolysaccharide inhalation
Change in the number of neutrophils in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Change in concentration of total protein in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Time frame: 6 hours after the LPS challenge
Change in concentration of total protein in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2018.
- Individual participant dataSharing planned: No
Related trials for Acute Lung Injury
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Muna Albayaty, MBBCh principal investigator
Parexel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imatinib in people with Acute Lung Injury, run by Exvastat Ltd. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the number of neutrophils in bronchoalveolar lavage fluid in subjects exposed to imatinib compared with placebo (time frame: 6 hours after lipopolysaccharide inhalation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2018.