Last updated: 11/07/2018 03:17:10
First time in human study (FTIH) with positron emission tomography (PET)
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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.
Trial description: This study described in the present protocol consists of two sections.Part A is the first administration into man to evaluate the safety, tolerability andpharmacokinetics of single ascending doses of GSK1144814. The study is a single-blind,randomised, placebo-controlled design in healthy male and female (of non-childbearingpotential) subjects. Part B will be an open-label design in healthy male subjects to assessthe GSK1144814 neurokinin-1 (NK1) receptor occupancy by positron emission tomography (PET)scanning with [11C]-GR205171
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Single (Investigator)
Allocation:
Randomized
Primary outcomes:
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).
Timeframe: 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),
Timeframe: 72 hours
Volume of distribution (VT) of [11C] GR205171 in the brain at Baseline and following oral doses of GSK1144814.
Timeframe: 7 days
NK1 receptor occupancy in the brain at Baseline and following oral doses of GSK1144814.
Timeframe: 7 days
Secondary outcomes:
Not applicable
Interventions:
Enrollment:
21
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Khanum Ridler, Roger N Gunn, Graham E Searle, Julien Barletta, Jan Passchier, Luanna Dixson, William A Hallett, Sharon Ashworth, Frank A Gray, Clare Burgess, Italo Poggesi, Jonathan N Bullman, E Ratti, MA Laruelle, Eugenii A Rabiner.Characterising the plasma-target occupancy relationship of the neurokinin antagonist GSK1144814 with PET.J Psychopharmacol.2014;28(3):244-253
Medical condition
Schizophrenia
Product
GSK1144814
Collaborators
Not applicable
Study date(s)
October 2008 to April 2009
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 55 years
Accepts healthy volunteers
Yes
- Healthy as determined by a responsible physician, based on a medical evaluation
- including medical history, physical examination, laboratory tests and cardiac
- 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,
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
- 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).
- 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.
A female subject is eligible to participate in Part A if she is of:
Exclusion criteria:
- 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).
- 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.
- 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
History of regular alcohol consumption within 6 months of the study start defined as:
Trial location(s)
Location
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA1 3UJ
Status
Will Be Recruiting
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2009-01-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 111321 can be found on the GSK Clinical Study Register.
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