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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01090440




Registration number
NCT01090440
Ethics application status
Date submitted
4/03/2010
Date registered
22/03/2010
Date last updated
22/06/2017

Titles & IDs
Public title
Pharmacokinetics, Effect of Food, Safety and Tolerability of a New Tablet Formulation of GSK1144814 in Healthy Subjects
Scientific title
An Open Label, Randomised, Three-way Cross-over Study to Evaluate the Pharmacokinetics, Effect of Food, Safety and Tolerability of a New Tablet Formulation of GSK1144814 in Healthy Male and Female Subjects
Secondary ID [1] 0 0
112891
Universal Trial Number (UTN)
Trial acronym
MNK112891
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK1144814

Experimental: Three-way cross- over - Three regimens will be administered in this study: A: GSK1144814 Tablet (100mg) Fasted State; B: GSK1144814 Tablet (200mg) Fasted State and C: GSK 1144814 Tablet (100mg) Fed State (FDA high fat breakfast).


Treatment: Drugs: GSK1144814
This study is an open label, randomised, three-way cross-over study to evaluate the pharmacokinetics, effect of food, safety and tolerability of a new tablet formulation of GSK1144814 in healthy male and female (non-child bearing potential) subjects. Sixteen subjects will be enrolled to provide a minimum number of 12 evaluable subjects. The doses to be administered will be 100 mg and 200mg in the fasted state, and 100mg following a high fat breakfast.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetics: tlag, Cmax, tmax, AUC(0-24), AUC(0 t), t½ and AUC(0 to infinity).
Timepoint [1] 0 0
2 months
Secondary outcome [1] 0 0
Safety and tolerability: AE monitoring, vital signs (blood pressure, heart rate, body temperature, electrocardiograms (ECGs) (12 lead and Holter), clinical laboratory assessments (standard laboratory parameters).
Timepoint [1] 0 0
2 months

Eligibility
Key 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 clinically significant abnormality or laboratory
parameters significantly outside the reference range for the population being studied
may be included only if the Investigator and the 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 or female between 18 and 65 years of age.

- A female subject is eligible to participate 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]
greater than 40 mIU/mL and oestradiol less than 40 pg/mL [less 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 draw; this interval depends on the type and dosage of
HRT. Following confirmation of their post menopausal status, they can resume use of HRT
during the study without use of a contraceptive method.

- Male subjects must agree to use one of the contraception methods alloed by the
protocol. This criterion must be followed from the first dosing day until 3 months
after the last dose.

- Body weight greater than or equal to 50 kg and BMI within the range 19 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.

- Demonstrates no evidence of mental impairment or co-morbid psychiatric disorders
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- History or presence of clinically significant cardiac arrhythmias, or other clinically
significant cardiac disease.

- QTcB or QTcF greater than 450 msec.

- Subjects, who in the investigator's judgement, pose a significant suicide risk.
Evidence of serious suicide risk may include any history of suicidal behavior and/or
any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months.

- 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). Additionally subjects with idiopathic haematuria or proteinuria or
conditions such as benign orthostatic proteinuria and benign familial haematuria
should be excluded from the study.

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco or
nicotine containing products within 6 months prior to Screening.

- Subjects, who in the investigator's judgement, pose a significant homicidal risk or
have ever been homicidal.

- 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 within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
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 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.

- History of regular alcohol consumption within 6 months of the study defined as the
following Australian guidelines:

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 270ml of
full strength beer, 470ml of light beer, 30ml of spirits and 100ml of wine.

- 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.

- 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 dosing day.

- Consumption of red wine from 7 days prior to the first dosing day.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/10/2009
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
GSK1144814 is a potent, insurmountable antagonist at human neurokinin-1 (NK1) and
neurokinin-3 (NK3) receptors with the potential to treat multiple symptom domains of
schizophrenia and be an efficacious antidepressant.

This study will be an open label, randomised, three-way cross-over study to evaluate the
safety, tolerability and pharmacokinetics of a new tablet formulation of GSK1144814 and to
evaluate the effect of food on single oral doses of GSK1144814 in healthy male and female
subjects.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01090440
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries