Last updated: 11/07/2018 05:13:30
An open label positron emission tomography study in healthy male subjects to investigate brain DAT and SERT occupancy,pharmacokinetics and safety of single oral doses of GSK1360707, using 11C- PE2I and 11C-DASB as PET ligands
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: An open label positron emission tomography study in healthy male subjects to investigate brain DAT and SERT occupancy, pharmacokinetics and safety of single oral doses ofGSK1360707, using 11C- PE2I and 11C-DASB as PET ligands
Trial description: GSK1360707 is a potent re-uptake inhibitor of the neurotransmitters dopamine, norepinephrine and serotonin. This is a single dose PET study in healthy subjects.A final analyses of safety data following exposure to single oral doses, from the first time in human study, with GSK1360707 has demonstrated that the compound is well tolerated up to a dose of 150mg. This imaging study will be an open label, non-randomised PET occupancy study using healthy male volunteers. The degree and time course of DAT and SERT occupancy by GSK1360707 will be determined. The PK/PD relationship between plasma concentrations of GSK1360707 and DAT and SERT occupancy will be described.This protocol amendment includes the flexibility to split the total dose into two doses e.g. 120mg per day could be split into two doses of 60mg. Splitting the total dose is most likely required to maintain therapeutic occupancy on the transporters over the course of the day; in addition it is expected that splitting the dose may reduce effects on vital signs. Therefore collecting data following split dosing will enable best predictions of therapeutic doses to be progressed in subsequent clinical studies.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
To estimate the degree of DAT occupancy in brain regions of interest (ROIs)following oral doses of GSK1360707 in healthy male subjects-To estimate the degree of SERT occupancy in brain ROIs following total oral doses of GSK1360707 in healthy male subject
Timeframe: 6-7 weeks.
To evaluate the relationship between the plasma concentration and the resultant DAT occupancy by GSK1360707.To evaluate the relationship between the plasma concentration and the resultant SERT occupancy by GSK1360707.
Timeframe: 6 - 7 weeks
Secondary outcomes:
To further assess the safety and tolerability of total oral doses of GSK1360707 including the maximal tolerated dose in the FTIH study (150 mg PO)-To further assess the pharmacokinetics of GSK1360707 in healthy male subjects
Timeframe: 6-7 weeks.
Interventions:
Enrollment:
12
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Depressive Disorder
Product
GSK1360707
Collaborators
Not applicable
Study date(s)
April 2009 to October 2009
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
35 - 55 years
Accepts healthy volunteers
Yes
- 1. 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 the
- Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- 1.Evidence or history of clinically significant hematological, renal, urinary / prostatic, endocrine, pulmonary, gastrointestinal, cardiovascular or other heart disease, glaucoma, diabetes, hepatic, neurologic (e.g. including but not limited to seizures, stroke, cerebrovascular disease or other brain conditions), or allergic disease (except for untreated, asymptomatic, seasonal allergies at time of dosing).
- 2. Psychiatric illness currently or within the past year, or any lifetime history of bipolar disorder, major depressive disorder, anxiety disorder, schizophrenia or other psychotic disorder, or substance abuse or dependence (except past history of nicotine abuse/dependence if >6 months prior to screening.
Inclusion and exclusion criteria
Inclusion criteria:
- 1. 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 the -Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. 2.Systolic blood pressure <140 mmHg, diastolic blood pressure <90 mmHg and heart rate <90 beats/min. 3. Male subjects between 35-55 years of age. 4.Male subjects must agree to use one of the contraception methods as listed in Section 8.1. 5.Body Mass Index (BMI) within the range 19 – 30 kg/m2 (inclusive) at screening visit. 6. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form 7.QTcB or QTcF < 450 msec (if the first QTcB reading exceeds the limits above, perform two more ECGs separated at least 5 min apart. Then take the average of the three QTcB to determine if the average satisfies the above criteria).
Exclusion criteria:
- 1.Evidence or history of clinically significant hematological, renal, urinary / prostatic, endocrine, pulmonary, gastrointestinal, cardiovascular or other heart disease, glaucoma, diabetes, hepatic, neurologic (e.g. including but not limited to seizures, stroke, cerebrovascular disease or other brain conditions), or allergic disease (except for untreated, asymptomatic, seasonal allergies at time of dosing). 2. Psychiatric illness currently or within the past year, or any lifetime history of bipolar disorder, major depressive disorder, anxiety disorder, schizophrenia or other psychotic disorder, or substance abuse or dependence (except past history of nicotine abuse/dependence if >6 months prior to screening. 3. Subjects who, in the investigator’s judgment, pose a suicidal or homicidal risk, or any subject with a history of suicidal or homicidal attempts or behaviour. 4. The subject has a positive pre-study drug/alcohol screen. 5. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 6. A positive test for HIV antibody. 7. History of regular excessive alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units. One unit is equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits or 1 glass (125mL) of wine. 8. 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: 90 days , 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 9. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 10. 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. 11. 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. 12. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 13. Unwillingness or inability to follow the procedures outlined in the protocol. 14. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. 15. Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication. 16. Controlled or uncontrolled hypertension, or systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥ 90 mmHg at screening or prior to the first dose of study medication. 17. 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). 18. History of, or suffers from, claustrophobia or feels that he will be unable to lie still on his back in the PET or MRI scanner for a period of 1-2 hours. 19. Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire. 20. Subjects who are smokers will be excluded from this study.
Trial location(s)
Location
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA1 3UJ
Status
Recruiting
Study documents
Clinical study report
Available language(s): English
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
2009-12-10
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 112773 can be found on the GSK Clinical Study Register.
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