SchizophreniaPhase 1NK1 NK3 PETNCT01209039
A Repeat Dose Positron Emission Tomography Study With GSK1144814
A Phase 1 study testing GSK1144814 in people with Schizophrenia, run by GlaxoSmithKline at 2 sites in United Kingdom.
Trial summary
This study described in the present protocol consists of two parts. Part A is a multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of ascending doses of GSK1144814. Part B is an open label design in healthy male subjects to assess the GSK1144814 Neurokinin1 receptor occupancy. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- GSK1144814
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Jul 2009to 25 Oct 2009
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if, in the opinion of the Investigator, the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female aged between 18 and 65 years (inclusive) for Part A, or male aged between 25 and 55 years (inclusive) for Part B.
- A female subject is eligible to participate in Part A if she is of:
- Non childbearing potential defined as pre menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] higher than 40 mIU/mL and oestradiol lower than 40 pg/mL [lower than 140 pmol/L] is confirmatory).
- Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to discontinue HRT to allow confirmation of post menopausal status prior to study enrolment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood sampling; this interval depends on the type and dosage of HRT. Following confirmation of their post menopausal status, they can resume the use of HRT during the study without the use of a contraceptive method.
- A male subject must agree to use one of the contraception methods listed in Section 8.1.2. This criterion must be followed from the first investigational product dosing day until at least 3 months after receiving the last dose of the investigational product.
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- Body weight higher than or equal to 50 kg and body mass index (BMI) within the range 18 to 29.9 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcB or QTcF lower than 450 msec.
- Demonstrates no evidence of mental impairment or co morbid psychiatric disorders or suicidal risk (as determined with the Columbia Suicide Severity Rating Scale [C SSRS]).
Who cannot join
- The subject has 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.
- A positive pre study hepatitis B surface antigen (HBsAg) or positive hepatitis C virus (HCV) antibody test result within 3 months of Screening.
- A positive test result for antibodies to human immunodeficiency virus (HIV) 1/2.
- Significant renal abnormality (from medical history or as indicated by laboratory investigations. In addition, subjects with idiopathic haematuria or proteinuria or conditions such as benign orthostatic proteinuria and benign familial haematuria should be excluded from the study).
- History of regular alcohol consumption within 6 months of the study start defined as:
- An average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half pint (220 mL) of beer or 1 measure (25 mL) of spirits or 1 glass (125 mL) of wine.
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- The subject has participated in a clinical trial and has received an investigational product within 3 month prior to the first investigational product dosing day in the current study.
- Exposure to more than four new chemical entities within 12 months prior to the first investigational product dosing day.
- 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 receiving the first dose of the investigational product, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the investigational products, 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 in the study.
- Where participation in the study would result in donation of blood or blood products in excess of 600 mL within a 56 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- History or presence of clinically significant cardiac arrhythmias, or other clinically significant cardiac disease.
- Smokers confirmed by a positive urinary cotinine test (greater than the local laboratory lower limit of quantification [LLQ] of 200 ng/mL or lower). Urine cotinine levels will be measured during Screening and at Baseline.
- Consumption of Seville oranges (including marmalade) and/or grapefruit and/or Chinese grapefruit (pomelo) and/or grapefruit hybrids and/or exotic citrus fruits and/or their fruit juices from 7 days prior to the first investigational product dosing day.
- Consumption of red wine from 7 days prior to the first investigational product dosing day.
- For Part B only:
- Abnormal Allen's test for adequate collateral blood flow to the hand.
- 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 International Commission on Radiological Protection (ICRP) Category IIb or above: No more than 10 mSv in addition to natural background radiation, in the previous 3 years including the dose from this study).
- Family history of cancer (one or more first degree relative diagnosed before the age of 55 years, inclusive).
- History of or suffers from claustrophobia or feels that they will be unable to lie still on their back in the PET camera for a period of approximately 2 hours.
- History of neurological or psychiatric conditions (e.g., stroke, traumatic brain injury, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischaemic attack, schizophrenia, major depression, etc) that may influence the outcome or analysis of the scan results.
- Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre MRI questionnaire supported by plain X rays where appropriate.
- Abnormal blood clotting profile, i.e., prolonged prothrombin time (INR).
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
GSK Investigational Site
Harrow, Middlesex, HA1 3UJ
GSK Investigational Site
London, W12 ONN
About this study
Official title: A Healthy Volunteer Repeat Dose Study to Evaluate; the Safety, Tolerability, Pharmacokinetics, Effects on the Pharmacokinetics of Midazolam and the Neurokinin 1 Receptor Occupancy of GSK1144814
This study described in the present protocol consists of two parts. Part A is a multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of ascending doses of GSK1144814. Part B is an open label design in healthy male subjects to assess the GSK1144814 Neurokinin1 receptor occupancy.
Read the detailed description
GSK1144814 is a dual Neurokinin 1 and Neurokinin 3 antagonist with the potential to treat schizophrenia and depression.
This study described in the present protocol consists of two parts. Part A is a multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of ascending doses of GSK1144814. The study is a single blind, randomised, placebo controlled design in healthy male and female (of non childbearing potential) subjects. Part B is an open label design in healthy male subjects to assess the GSK1144814 Neurokinin 1 receptor occupancy after repeat oral dosing by positron emission tomography scanning with [11C] GR205171.
- Conditions
- Schizophrenia
- Being tested
- GSK1144814
- Keywords
- Schizophrenia, PET
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1144814Drug
Multiple daily doses of GSK1144814 for 28 days
GSK1144814Drug
Multiple daily doses of GSK1144814 for 14 days
GSK1144814Drug
Multiple daily doses of GSK1144814 for 7 days (or until steady state is reached)
| Study group | Role | What they receive |
|---|---|---|
| Part A, cohort 1 and 2 | Experimental | Part A, Cohorts 1 and 2, will investigate escalating multiple daily doses of GSK1144814 in 19 subjects Receives: Drug: GSK1144814 |
| Part A, cohort 3 | Experimental | Cohort 3 will investigate safety, tolerability and PK of a dose of GSK1144814 over a repeat treatment period of 28 days in 18 subjects and a potential drug drug interaction between GSK1144814 and the CYP3A4 sensitive substrate midazolam (in 15 subjects). Receives: Drug: GSK1144814 |
| Part B | Experimental | Part B will assess NK1 receptor occupancy following repeated administration of GSK1144814 given once daily until steady state is obtained Receives: Drug: GSK1144814 |
What is being measured
The primary outcome is the main question the study is designed to answer.
PET receptor occupancy
Measured: 1 week
To assess the safety and tolerability by reviewing the number of subjects with adverse events, a review of laboratory samples and a review of vitals.
Measured: 2 or 4 weeks
To review pharmacokinetic data
Measured: 2 or 4 weeks
Secondary outcomes (1)
To assess potential induction of CYP3A4
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2010 (estimated)
- Study start1 Jul 2009
- Primary completion25 Oct 2009
- Study completion25 Oct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 41 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
- NCT01209039
- Sponsor's protocol ID
- 111587
- Acronym
- NK1 NK3 PET
- Status last verified
- Jun 2017
- First submitted
- 30 Aug 2010
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Healthy Volunteer Repeat Dose Study to Evaluate; the Safety, Tolerability, Pharmacokinetics, Effects on the Pharmacokinetics of Midazolam and the Neurokinin 1 Receptor Occupancy of GSK1144814
- ClinicalTrials.gov ID
- NCT01209039
- Acronym / sponsor ID
- NK1 NK3 PET / 111587
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, PET
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2009 (actual)
- Primary completion
- 25 Oct 2009 (actual)
- Study completion
- 25 Oct 2009 (actual)
- First posted
- 24 Sep 2010 (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 study described in the present protocol consists of two parts. Part A is a multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of ascending doses of GSK1144814. Part B is an open label design in healthy male subjects to assess the GSK1144814 Neurokinin1 receptor occupancy.
Detailed description
GSK1144814 is a dual Neurokinin 1 and Neurokinin 3 antagonist with the potential to treat schizophrenia and depression.
This study described in the present protocol consists of two parts. Part A is a multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of ascending doses of GSK1144814. The study is a single blind, randomised, placebo controlled design in healthy male and female (of non childbearing potential) subjects. Part B is an open label design in healthy male subjects to assess the GSK1144814 Neurokinin 1 receptor occupancy after repeat oral dosing by positron emission tomography scanning with [11C] GR205171.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A, cohort 1 and 2 | Experimental | Drug: GSK1144814Part A, Cohorts 1 and 2, will investigate escalating multiple daily doses of GSK1144814 in 19 subjects |
| Part A, cohort 3 | Experimental | Drug: GSK1144814Cohort 3 will investigate safety, tolerability and PK of a dose of GSK1144814 over a repeat treatment period of 28 days in 18 subjects and a potential drug drug interaction between GSK1144814 and the CYP3A4 sensitive substrate midazolam (in 15 subjects). |
| Part B | Experimental | Drug: GSK1144814Part B will assess NK1 receptor occupancy following repeated administration of GSK1144814 given once daily until steady state is obtained |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if, in the opinion of the Investigator, the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female aged between 18 and 65 years (inclusive) for Part A, or male aged between 25 and 55 years (inclusive) for Part B.
- A female subject is eligible to participate in Part A if she is of:
- Non childbearing potential defined as pre menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] higher than 40 mIU/mL and oestradiol lower than 40 pg/mL [lower than 140 pmol/L] is confirmatory).
- Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to discontinue HRT to allow confirmation of post menopausal status prior to study enrolment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood sampling; this interval depends on the type and dosage of HRT. Following confirmation of their post menopausal status, they can resume the use of HRT during the study without the use of a contraceptive method.
Key exclusion criteria (24 listed)
- The subject has 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.
- A positive pre study hepatitis B surface antigen (HBsAg) or positive hepatitis C virus (HCV) antibody test result within 3 months of Screening.
- A positive test result for antibodies to human immunodeficiency virus (HIV) 1/2.
- Significant renal abnormality (from medical history or as indicated by laboratory investigations. In addition, subjects with idiopathic haematuria or proteinuria or conditions such as benign orthostatic proteinuria and benign familial haematuria should be excluded from the study).
- History of regular alcohol consumption within 6 months of the study start defined as:
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 |
|---|---|---|
| GSK1144814Multiple daily doses of GSK1144814 for 28 days | Drug | Part A, cohort 3 |
| GSK1144814Multiple daily doses of GSK1144814 for 14 days | Drug | Part A, cohort 1 and 2 |
| GSK1144814Multiple daily doses of GSK1144814 for 7 days (or until steady state is reached) | Drug | Part B |
Primary outcome
PET receptor occupancy
Time frame: 1 week
To assess the safety and tolerability by reviewing the number of subjects with adverse events, a review of laboratory samples and a review of vitals.
Time frame: 2 or 4 weeks
To review pharmacokinetic data
Time frame: 2 or 4 weeks
1 secondary outcome
To assess potential induction of CYP3A4
Time frame: up to 4 weeks
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 20 Jun 2017.
- Results for study 111587 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK1144814 in people with Schizophrenia, run by GlaxoSmithKline at 2 sites 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 10 inclusion and 24 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 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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?
PET receptor occupancy (time frame: 1 week). The study lists 3 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 20 Jun 2017.