Alzheimer's DiseasePhase 1NCT01924858
A Positron Emission Tomography (PET) Study to Investigate the Brain Biodistribution of 18F GSK2647544 in Healthy Subjects to Determine Its Ability to Cross the Blood-brain-barrier.
A Phase 1 study testing GSK2647544 oral and [18F]GSK2647544 IV bolus in people with Alzheimer's Disease, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This is an open label, PET study in healthy male subjects to determine if GSK2647544 is able to cross the blood-brain-barrier. The study will use GSK2647544 radiolabelled with fluorine-18 ([18F] GSK2647544) to determine the ratio of the concentration of the compound in tissue to that in plasma at equilibrium… Read more about this study
- Who is it for?
- Ages 30 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- GSK2647544 oral and [18F]GSK2647544 IV bolus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 19 Aug 2013to 3 Mar 2014
- 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 30 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical significant abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male subject between 30 and 55 years of age inclusive, at the time of signing the informed consent.
- Male subjects must agree to use one of the contraception methods. This criterion must be followed from the time the first administration of GSK2647544 until completion of the study and for 4 months after dosing.
- Body weight >=50 kilogram and body mass index within the range 19.0 to 29.0 kilogram per square meter (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test.
Who cannot join
- A screening ECG with a corrected QT (QTc) value, of<350 milliseconds (msec) or >450msec (triplicate ECGs) and/or a PR interval outside the range 120 to 220 msec (triplicate ECGs) or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave)
- Pulse rate <45 or >90 beats per minute or a systolic BP >140 or <90 or a diastolic BP >90 or <60 millimeter of mercury (mmHg).
- History of long QT syndrome (personal or family) or other cardiac conduction disorder, a history of sudden unexplained death or unexplained syncope in a first degree relative or other clinically significant cardiac disease.
- Subjects with current or past diagnosis of cardiovascular disease including but not limited to hypertension, cardiac arrhythmias and/or risk factors for coronary artery disease.
- Current or recent (within one year) gastrointestinal disease; a history of mal-absorption, oesophageal reflux, irritable bowel syndrome; frequent (more than once a week) occurrence of heartburn; or any surgical intervention (e.g., cholecysectomy) which would be expected to influence the absorption of drugs.
- History of asthma, anaphylaxis or anaphalactoid reactions, severe allergic responses
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- History of hypercoagulable state or history of thrombosis
- Subjects who have current renal or history of clinically significant renal abnormalities.
- History or presence of a neurological or psychiatric diagnosis (not limited to but including for example, stroke, traumatic brain injury, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, major depression etc) that in the opinion of the investigator may influence the outcome or analysis of the scan results.
- Subject is mentally or legally incapacitated.
- 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) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- History of regular alcohol consumption within 6 months of the study defined as:
- An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 millilitre [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- A positive pre-study Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody result within 3 months of screening
- A positive test for human immunodeficiency virus (HIV) antibody.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- The subject has participated in a clinical trial and has received an investigational product (IP) within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the IP (whichever is longer).
- Exposure to more than three new chemical entities within 12 months prior to the first dosing day.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden (a significant radiation burden being defined as >10 millisievert [mSv] in addition to natural background radiation in the previous 3 years).
- Worked as a welder, metal worker or machinist.
- History of, or suffers from, claustrophobia or feels that he will be unable to lie still on his back in the PET or MRI scanner for a period of 1 to 2 hours.
- Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label Positron Emission Tomography (PET) Study to Investigate the Brain Biodistribution of 18F-GSK2647544 in Healthy Subjects
This is an open label, PET study in healthy male subjects to determine if GSK2647544 is able to cross the blood-brain-barrier. The study will use GSK2647544 radiolabelled with fluorine-18 ([18F] GSK2647544) to determine the ratio of the concentration of the compound in tissue to that in plasma at equilibrium, expressed as the PET volume of distribution (VT). The study will consist of at least four visits; 2 screening visits, scanning day and follow-up. On Day 1 (scanning day) the subject will receive a single oral dose of GSK2647544 (100 mg) followed approximately 2 hours later by a single intravenous (IV) infusion of [18F]-GSK2647544 and a dynamic PET scan. Arterial and venous blood sampling will be used to determine the plasma kinetics of [18F]-GSK2647544 and unlabeled GSK2647544. In addition, each subject will undergo a structural magnetic resonance imaging (MRI) scan of the brain to aid in the definition of neuroanatomy. The dose of GSK2647544 was selected based on the review of the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) data obtained in the first time in human (FTIH) study.
- Conditions
- Alzheimer's Disease
- Being tested
- GSK2647544 oral, [18F]GSK2647544 IV bolus
- Keywords
- PET, healthy subjects, Lp-PLA2, positron emission tomography, Alzheimer's disease, brain exposure, GSK2647544
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2647544 oralDrug
GSK2647544 100 mg will be supplied as a size 0 swedish orange hard gelatin capsules filled with white/slightly colored granule. Subjects will receive a single oral dose of GSK2647544 100 mg (2 X 50mg capsules) with 150 mL of tepid water approximately 2 hours prior to the IV infusion of [18F]-GSK2647544 and a PET scan.
[18F]GSK2647544 IV bolusDrug
[18F]GSK2647544 will be supplied as a clear, colourless solution free from visible particle. A maximum dose up to 2 mg with a maximum dose volume of 25 mL will be administered as IV bolus over 60 seconds.
| Study group | Role | What they receive |
|---|---|---|
| GSK2647544 oral and [18F]GSK2647544 IV bolus | Experimental | All subjects will receive a single oral dose of GSK2647544 100 milligram (mg) approximately 2 hours before administration of [18F] GSK2647544 and a dynamic PET scan. [18F]-GSK2647544 will be administered to the subject as an IV bolus during the PET scan, which will be conducted for up to 120 minute post the injection of [18F]GSK2647544 Receives: Drug: GSK2647544 oral; Drug: [18F]GSK2647544 IV bolus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole brain PET VT of [18F]-GSK2647544
The subject will be administered GSK2647544 radiolabelled with fluorine-18 ([18F]-GSK2647544) to determine the ratio of the concentration of the compound in tissue to that in plasma at equilibrium, expressed as the PET VT
Measured: At Day 1
Secondary outcomes (2)
Safety and tolerability assessment following oral administration of GSK2647544
The safety and tolerability assessment including adverse events assessment; clinical hematology, clinical chemistry, urinalysis and renal function tests; single 12-lead electrocardiograms (ECGs) and vital sign measurements including systolic and diastolic blood pressure (BP), pulse rate and respiratory rate.
Measured: Up to Day 14
GSK2647544 PK assessment
Blood sample will be collected for PK analysis of GSK2647544 including maximum observed plasma concentration (Cmax) and time to Cmax (tmax).
Measured: Pre dose and at 30minute, 1, 2, 4, 6 hours post dose on Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2013 (estimated)
- Study start19 Aug 2013
- Primary completion3 Mar 2014
- Study completion3 Mar 2014
Why it stopped: Study objectives met so study concluded earlier than planned hence we terminated the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01924858
- Sponsor's protocol ID
- 117155
- Other IDs
- 2013-000919-25
- Status last verified
- Oct 2020
- First submitted
- 15 Aug 2013
- Last updated
- 9 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Huiban M, Coello C, Wu K, Xu Y, Lewis Y, Brown AP, Buraglio M, Guan C, Shabbir S, Fong R, Passchier J, Rabiner EA, Lockhart A. Investigation of the Brain Biodistribution of the Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitor [18F]GSK2647544 in Healthy Male Subjects. Mol Imaging Biol. 2017 Feb;19(1):153-161. doi: 10.1007/s11307-016-0982-5.
PubMed 27402093
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Positron Emission Tomography (PET) Study to Investigate the Brain Biodistribution of 18F-GSK2647544 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01924858
- Acronym / sponsor ID
- 117155
- Conditions
- Alzheimer's Disease
- Keywords
- PET, healthy subjects, Lp-PLA2, positron emission tomography, Alzheimer's disease, brain exposure, GSK2647544
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study objectives met so study concluded earlier than planned hence we terminated the study.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2013 (actual)
- Primary completion
- 3 Mar 2014 (actual)
- Study completion
- 3 Mar 2014 (actual)
- First posted
- 19 Aug 2013 (estimated)
- 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.
This is an open label, PET study in healthy male subjects to determine if GSK2647544 is able to cross the blood-brain-barrier. The study will use GSK2647544 radiolabelled with fluorine-18 ([18F] GSK2647544) to determine the ratio of the concentration of the compound in tissue to that in plasma at equilibrium, expressed as the PET volume of distribution (VT). The study will consist of at least four visits; 2 screening visits, scanning day and follow-up. On Day 1 (scanning day) the subject will receive a single oral dose of GSK2647544 (100 mg) followed approximately 2 hours later by a single intravenous (IV) infusion of [18F]-GSK2647544 and a dynamic PET scan. Arterial and venous blood sampling will be used to determine the plasma kinetics of [18F]-GSK2647544 and unlabeled GSK2647544. In addition, each subject will undergo a structural magnetic resonance imaging (MRI) scan of the brain to aid in the definition of neuroanatomy. The dose of GSK2647544 was selected based on the review of the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) data obtained in the first time in human (FTIH) study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2647544 oral and [18F]GSK2647544 IV bolus | Experimental | Drug: GSK2647544 oral, Drug: [18F]GSK2647544 IV bolusAll subjects will receive a single oral dose of GSK2647544 100 milligram (mg) approximately 2 hours before administration of [18F] GSK2647544 and a dynamic PET scan. [18F]-GSK2647544 will be administered to the subject as an IV bolus during the PET scan, which will be conducted for up to 120 minute post the injection of [18F]GSK2647544 |
Who may qualify
- Ages
- 30 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical significant abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male subject between 30 and 55 years of age inclusive, at the time of signing the informed consent.
- Male subjects must agree to use one of the contraception methods. This criterion must be followed from the time the first administration of GSK2647544 until completion of the study and for 4 months after dosing.
- Body weight >=50 kilogram and body mass index within the range 19.0 to 29.0 kilogram per square meter (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Key exclusion criteria (26 listed)
- A screening ECG with a corrected QT (QTc) value, of<350 milliseconds (msec) or >450msec (triplicate ECGs) and/or a PR interval outside the range 120 to 220 msec (triplicate ECGs) or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave)
- Pulse rate <45 or >90 beats per minute or a systolic BP >140 or <90 or a diastolic BP >90 or <60 millimeter of mercury (mmHg).
- History of long QT syndrome (personal or family) or other cardiac conduction disorder, a history of sudden unexplained death or unexplained syncope in a first degree relative or other clinically significant cardiac disease.
- Subjects with current or past diagnosis of cardiovascular disease including but not limited to hypertension, cardiac arrhythmias and/or risk factors for coronary artery disease.
- Current or recent (within one year) gastrointestinal disease; a history of mal-absorption, oesophageal reflux, irritable bowel syndrome; frequent (more than once a week) occurrence of heartburn; or any surgical intervention (e.g., cholecysectomy) which would be expected to influence the absorption of drugs.
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 |
|---|---|---|
| GSK2647544 oralGSK2647544 100 mg will be supplied as a size 0 swedish orange hard gelatin capsules filled with white/slightly colored granule. Subjects will receive a single oral dose of GSK2647544 100 mg (2 X 50mg capsules) with 150 mL of tepid water approximately 2 hours prior to the IV infusion of [18F]-GSK2647544 and a PET scan. | Drug | GSK2647544 oral and [18F]GSK2647544 IV bolus |
| [18F]GSK2647544 IV bolus[18F]GSK2647544 will be supplied as a clear, colourless solution free from visible particle. A maximum dose up to 2 mg with a maximum dose volume of 25 mL will be administered as IV bolus over 60 seconds. | Drug | GSK2647544 oral and [18F]GSK2647544 IV bolus |
Primary outcome
Whole brain PET VT of [18F]-GSK2647544
Time frame: At Day 1
The subject will be administered GSK2647544 radiolabelled with fluorine-18 ([18F]-GSK2647544) to determine the ratio of the concentration of the compound in tissue to that in plasma at equilibrium, expressed as the PET VT
2 secondary outcomes
Safety and tolerability assessment following oral administration of GSK2647544
Time frame: Up to Day 14
GSK2647544 PK assessment
Time frame: Pre dose and at 30minute, 1, 2, 4, 6 hours post dose on Day 1
Results and safety
The study was stopped early (reason given: Study objectives met so study concluded earlier than planned hence we terminated the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2020.
- Background: PubMed 27402093Huiban M, Coello C, Wu K, Xu Y, Lewis Y, Brown AP, Buraglio M, Guan C, Shabbir S, Fong R, Passchier J, Rabiner EA, Lockhart A. Investigation of the Brain Biodistribution of the Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitor [18F]GSK2647544 in Healthy Male Subjects. Mol Imaging Biol. 2017 Feb;19(1):153-161. doi: 10.1007/s11307-016-0982-5.
- Individual participant dataSharing planned: No
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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.
GSK Clinical Trials study director
GlaxoSmithKline
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 GSK2647544 oral and [18F]GSK2647544 IV bolus in people with Alzheimer's Disease, run by GlaxoSmithKline 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 6 inclusion and 26 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: stopped early, as of the sponsor's last update on 9 Oct 2020. 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. 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 was stopped early (reason given: Study objectives met so study concluded earlier than planned hence we terminated the study.). Results are not available in the source record.
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?
Whole brain PET VT of [18F]-GSK2647544 (time frame: At Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01924858, which also lists 1 linked publication.
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 9 Oct 2020.