SchizophreniaPhase 1NCT01381419
First Time in Human Study (FTIH) With Positron Emission Tomography (PET)
A Phase 1 study testing GSK1144814 in people with Schizophrenia, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This study described in the present protocol consists of two sections. Part A is the first administration into man to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of GSK1144814. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- GSK1144814
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Oct 2008to 1 Apr 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 55 years
- All sexes
- Healthy volunteers accepted
- 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 55 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] >40 mIU/mL and oestradiol <40 pg/mL [<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. 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.
- Body weight ≥50 kg and body mass index (BMI) within the range 18 to 29.9 kg/m2 (inclusive).
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- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcB or QTcF <450 msec.
- Demonstrates no evidence of mental impairment or co-morbid psychiatric disorders.
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 500 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Harrow, Middlesex, HA1 3UJ
About this study
Official title: A Single-blind, Randomised, Placebo-controlled, Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK1144814 in Healthy Male and Female Subjects and an Open-label Positron Emission Tomography Study in Healthy Male Subjects to Evaluate the Neurokinin-1 (NK1) Receptor Occupancy of GSK1144814 in the Living Human Brain Using 11C GR205171.
This study described in the present protocol consists of two sections. Part A is the first administration into man to evaluate the safety, tolerability and pharmacokinetics of single 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 will be an open-label design in healthy male subjects to assess the GSK1144814 neurokinin-1 (NK1) receptor occupancy by positron emission tomography (PET) scanning with [11C]-GR205171
Read the detailed description
GSK1144814 is a dual neurokinin-1 (NK1) and neurokinin-3 (NK3) antagonist with the potential to treat schizophrenia \& depression.
This study described in the present protocol consists of two sections. Part A is the first administration into man to evaluate the safety, tolerability and pharmacokinetics of single 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 will be an open-label design in healthy male subjects to assess the GSK1144814 NK1 receptor occupancy by positron emission tomography (PET) scanning with [11C]-GR205171.
- Conditions
- Schizophrenia
- Being tested
- GSK1144814
- Keywords
- pharmacokinetics, safety, positron emission tomography (PET), single ascending dose
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1144814Drug
Single dose.
GSK1144814Drug
Single dose which may be split in up to three divided doses given 2 to 3 hours apart.
GSK1144814Drug
Single dose that may be split in up to three divided doses given 2 to 3 hours apart.
| Study group | Role | What they receive |
|---|---|---|
| Part A, Cohort 1 | Experimental | In Cohort 1, four subjects (two on active and two on placebo for first dose, and then three on active and one on placebo for subsequent doses) will be included. Subjects will be dosed at least 30 minutes apart over the dosing day and only doses administered where the predicted plasma concentration will remain below those corresponding to the MABEL. Receives: Drug: GSK1144814 |
| Part A, cohort 2 | Experimental | In Cohort 2, 10 subjects will be included (8 active : 2 placebo). Dosing will start once the previous cohort (Cohort 1) has completed the Treatment Phase. For Cohort 2 and any subsequent cohorts, dosing will take place on two different days when a new dose is administered such that no more than one subject receives the agreed ascending dose on the first dosing day. Doses may be split in up to three divided doses given 2 to 3 hours apart. Dosing for the first four sessions in each cohort will be staggered over 2 days. On the first day of each dosing session, only one subject will receive the highest dose for that dosing session and at least one subject each will receive placebo. The remaining subjects in the cohort will be dosed on the second day according to the randomisation plan. Receives: Drug: GSK1144814 |
| Part B | Experimental | Part B of the study will consist of a Screening Visit (up to 30 days before the dosing session), three PET scans (where possible, all three scans may be performed in one visit when subject is admitted overnight) and a Follow-up Visit. Each subject will receive an oral dose of study drug. The dose may be split in up to three divided doses given 2 to 3 hours apart. Receives: Drug: GSK1144814 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability: Adverse event monitoring, vital signs (blood pressure, heart rate, respiratory rate, oral body temperature, ECGs (12 lead and Holter), clinical laboratory assessments (standard laboratory parameters).
Measured: 2 months
Pharmacokinetics: time-point immediately prior to the first quantifiable plasma concentration (tlag), Cmax, time of occurrence of Cmax (tmax), AUC from time zero (pre dose) to the time of the last quantifiable concentration (AUC0-infinity),
Measured: 72 hours
Volume of distribution (VT) of [11C] GR205171 in the brain at Baseline and following oral doses of GSK1144814.
Measured: 7 days
NK1 receptor occupancy in the brain at Baseline and following oral doses of GSK1144814.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study start20 Oct 2008
- Primary completion1 Apr 2009
- Study completion1 Apr 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
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 21 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
- NCT01381419
- Sponsor's protocol ID
- 111321
- Status last verified
- Jul 2017
- First submitted
- 9 Jun 2011
- Last updated
- 7 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-blind, Randomised, Placebo-controlled, Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK1144814 in Healthy Male and Female Subjects and an Open-label Positron Emission Tomography Study in Healthy Male Subjects to Evaluate the Neurokinin-1 (NK1) Receptor Occupancy of GSK1144814 in the Living Human Brain Using 11C GR205171.
- ClinicalTrials.gov ID
- NCT01381419
- Acronym / sponsor ID
- 111321
- Conditions
- Schizophrenia
- Keywords
- pharmacokinetics, safety, positron emission tomography (PET), single ascending dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 20 Oct 2008 (actual)
- Primary completion
- 1 Apr 2009 (actual)
- Study completion
- 1 Apr 2009 (actual)
- First posted
- 27 Jun 2011 (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 sections. Part A is the first administration into man to evaluate the safety, tolerability and pharmacokinetics of single 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 will be an open-label design in healthy male subjects to assess the GSK1144814 neurokinin-1 (NK1) receptor occupancy by positron emission tomography (PET) scanning with [11C]-GR205171
Detailed description
GSK1144814 is a dual neurokinin-1 (NK1) and neurokinin-3 (NK3) antagonist with the potential to treat schizophrenia \& depression.
This study described in the present protocol consists of two sections. Part A is the first administration into man to evaluate the safety, tolerability and pharmacokinetics of single 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 will be an open-label design in healthy male subjects to assess the GSK1144814 NK1 receptor occupancy by positron emission tomography (PET) scanning with [11C]-GR205171.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A, Cohort 1 | Experimental | Drug: GSK1144814In Cohort 1, four subjects (two on active and two on placebo for first dose, and then three on active and one on placebo for subsequent doses) will be included. Subjects will be dosed at least 30 minutes apart over the dosing day and only doses administered where the predicted plasma concentration will remain below those corresponding to the MABEL. |
| Part A, cohort 2 | Experimental | Drug: GSK1144814In Cohort 2, 10 subjects will be included (8 active : 2 placebo). Dosing will start once the previous cohort (Cohort 1) has completed the Treatment Phase. For Cohort 2 and any subsequent cohorts, dosing will take place on two different days when a new dose is administered such that no more than one subject receives the agreed ascending dose on the first dosing day. Doses may be split in up to three divided doses given 2 to 3 hours apart. Dosing for the first four sessions in each cohort will be staggered over 2 days. On the first day of each dosing session, only one subject will receive the highest dose for that dosing session and at least one subject each will receive placebo. The remaining subjects in the cohort will be dosed on the second day according to the randomisation plan. |
| Part B | Experimental | Drug: GSK1144814Part B of the study will consist of a Screening Visit (up to 30 days before the dosing session), three PET scans (where possible, all three scans may be performed in one visit when subject is admitted overnight) and a Follow-up Visit. Each subject will receive an oral dose of study drug. The dose may be split in up to three divided doses given 2 to 3 hours apart. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 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 55 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:
- A male subject must agree to use one of the contraception methods listed in Section 8.1. 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.
- Body weight ≥50 kg and body mass index (BMI) within the range 18 to 29.9 kg/m2 (inclusive).
Key exclusion criteria (16 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 |
|---|---|---|
| GSK1144814Single dose. | Drug | Part A, Cohort 1 |
| GSK1144814Single dose which may be split in up to three divided doses given 2 to 3 hours apart. | Drug | Part A, cohort 2 |
| GSK1144814Single dose that may be split in up to three divided doses given 2 to 3 hours apart. | Drug | Part B |
Primary outcome
Safety and tolerability: Adverse event monitoring, vital signs (blood pressure, heart rate, respiratory rate, oral body temperature, ECGs (12 lead and Holter), clinical laboratory assessments (standard laboratory parameters).
Time frame: 2 months
Pharmacokinetics: time-point immediately prior to the first quantifiable plasma concentration (tlag), Cmax, time of occurrence of Cmax (tmax), AUC from time zero (pre dose) to the time of the last quantifiable concentration (AUC0-infinity),
Time frame: 72 hours
Volume of distribution (VT) of [11C] GR205171 in the brain at Baseline and following oral doses of GSK1144814.
Time frame: 7 days
NK1 receptor occupancy in the brain at Baseline and following oral doses of GSK1144814.
Time frame: 7 days
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 7 Jul 2017.
- Results for study 111321 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
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 GSK1144814 in people with Schizophrenia, 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 9 inclusion and 16 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 7 Jul 2017. 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 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?
Safety and tolerability: Adverse event monitoring, vital signs (blood pressure, heart rate, respiratory rate, oral body temperature, ECGs (12 lead and Holter), clinical laboratory assessments (standard laboratory parameters). (time frame: 2 months). The study lists 4 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 7 Jul 2017.