Study of Safety, Blood Levels and Brain Receptor Occupancy of GSK598809 Using PET Imaging in Health Males.

Healthy Subjects Clinical Trial

Official title:

An Open Label Positron Emission Tomography Study in Healthy Male Subjects to Investigate Brain Dopamine D3 Occupancy Kinetics, Pharmacokinetics and Safety of Single Oral Doses of GSK598809, Using [11C]-(+)-PHNO as PET Ligand.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468806
• Other study ID #: DAN106589
• Status: Completed
• Phase: Phase 1
• First received: May 1, 2007
• Last updated: October 14, 2010
• Start date: April 2007
• Est. completion date: May 2008

Study information

• Verified date: October 2010
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCanada: Therapetic Products Directorate
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to look at how much of a new drug, GSK598809 binds to specific proteins in the brain and how much stays in the blood over a range of different doses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 25 Years to 55 Years

Eligibility

Inclusion Criteria:

Healthy male subjects, defined as individuals who are free from clinically significant illness or disease as determined by their medical history (including family), physical examination, laboratory studies, and other tests.

• Aged 25-55 years inclusive, at screening visit.

• Body weight > 50 kg and body mass index (BMI) between 19.0 - 29.0 kg/m2 inclusive.

• Capable of giving informed consent and can comply with the study requirements and timetable.

• Self-administered Beck Depression Inventory II scale total score no greater than 9, and suicide question score of zero.

• Able to read, comprehend and record information.

• A signed and dated written informed consent is obtained from the subject.

Exclusion Criteria:

• The physician responsible considers the subject unfit for the study based upon medical history, physical examination and psychiatric history and evaluation.

• History of a drug or other allergy which in the opinion of the physician responsible contraindicates their participation in the study.

• Participation in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug(whichever is longer) prior to the first dose of current study medication.

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• A screening ECG outside of ranges specified in the protocol

• Pulse rate <55 or >100 bpm OR a systolic blood pressure >140 and <100 OR a diastolic blood pressure >90 and <60.

• History of long QT syndrome (personal or family) or other cardiac conduction disorder, or other clinically significant cardiac disease.

• An electrolyte value outside the normal range at pre-study screening. Subjects who do not fall within the normal reference ranges may be included within the study if in the opinion of the Principal Investigator and Medical Monitor this will not compromise the subject.

• Liver function tests (LFT) elevated above the reference range at pre-study screening that remain elevated with a repeat LFT.

• Any other clinically significant laboratory abnormality.

• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John'sWort) 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 sponsor the medication will not interfere with the study procedures or compromise subject safety.

• History of regular alcohol consumption averaging >14 drinks/week for men. One drink is equivalent to(12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits) within 6 months of screening.

• Smokes or has smoked in the last 6 months.

• Donation of more than 450 ml blood within the 56 days before dosing.

• An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of administration of study medication (GSK598809) until 90 days following administration of study medication or an unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception if the woman could become pregnant from the time of administration of study medication until 90 days following administration of study medication.

• Current or recent (within one year) gastrointestinal disease; a history of malabsorption, esophageal 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.

• Any previous or current psychiatric diagnosis listed in DSMIV Axis I or II.

• Any history of suicidal attempts, suicidal ideation or behaviour.

• Chronic Hepatitis B and C, as evidenced by positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody.

• A positive test for HIV.

• Past history of drug abuse (i.e. meeting DSM IV or ICD 10 criteria for substance dependence) or has tested positive for urine drugs of abuse at pre-study screening and/or prior to dosing.

• 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 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).

• 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 2 hours.

• History or presence of a neurological 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 may influence the outcome or analysis of the scan results.

• Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• GSK598809, using [11C]-(+)-PHNO

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	%D3 RO at Tmax		approx 1.5 hrs
Primary	Percentage occupancy at Tmax		approx 1.5 hrs
Primary	Ttrough		approx 24 hrs
Primary	time course of GSK598809 plasma concentration following a single oral dose of GSK598809		at predose,1,1.5,2,3,4,8,24 and 48 hrs.
Secondary	Prolactin/TSH levels		at predose,1, 2, 4,8 & 24 hrs postdose
Secondary	Akathisia		at baseline at 1, 4 hrs postdose
Secondary	EPQ, BIS-BAS:		at screening
Secondary	POMS, CRT:		at predose & 4 hrs postdose
Secondary	VAS:		at predose, 1, 4 hrs postdose
Secondary	LSEQ		at screening, baseline scan & 24 hrs
Secondary	neuroendocrine and behavioural measures following GSK598809 administration.