Clinical trial NCT00743405: Safety, Tolerability and Pharmacokinetics of GSK1034702 in Healthy Subjects
Official title: Single-blind, Randomised, Placebo Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK1034702 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cognitive Disorders
Keywords: schizophrenia
M1 receptor agonist
safety
pharmacokinetics
GSK1034702
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-08-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a First Time in Human Study to assess the safety, tolerability and pharmacokinetics of single doses of GSK1034702 in healthy subjects. It will be a single-blind, randomized, placebo-controlled, single oral dose, dose-rising, cross-over study in healthy male and female (of non-child bearing potential) subjects. Subjects will be randomized into cohorts of 10 subjects and cohorts will be recruited until the pre-defined safety or PK stopping limits are reached. Each subject will receive placebo and up to 4 doses of GSK1034702 in a randomized sequence on 5 separate study occasions.


Eligibility criteria: Inclusion Criteria:

* Healthy as determined by a responsible physician, based on a medical evaluation including own and familial medical history, physical examination, laboratory tests and cardiac monitoring.
* Male or female between 18 and 55 years of age.
* A female subject is eligible to participate if she is of non-childbearing potential
* Body weight \> 50 kg and BMI within the range 19 - 29.9 kg/m2 (inclusive).
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* Capable of reading, comprehending and writing English at a sufficient level to complete study-related materials.
* Demonstrates no evidence of mental impairment.
* No co-morbid Psychiatric Disorders as defined using the Mini International Neuropsychiatric Interview

Exclusion Criteria:

* A positive pre-study drug/alcohol screen.
* A positive pre-study Hepatitis B , Hepatitis C or HIV.
* History of regular alcohol consumption.
* 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 .
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
* Pregnant females, females planning pregnancy or lactating females.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Subjects with a current or a history of psychiatric illness.
* Subjects with any history of suicidal attempts or behavior.
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products.
* Consumption of red wine, seville oranges, grapefruit or grapefruit juice (and pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices) from 7 days prior to the first dose of study medication.

Primary outcomes:
measure: •Safety and tolerability determined by adverse events; ECG; Holter; blood pressure, heart rate, respiration rate; clinical laboratory evaluations, pupil size & temperature.•Blood concentrations of GSK1034702.
timeFrame: 20 weeks
Secondary outcomes:
measure: Assessment of the Bond-Lader Visual Analogue Scale.
timeFrame: 20 weeks
measure: Assessment of exploratory PD markers: neuroendocrine markers, e.g. growth hormone.
timeFrame: 20 weeks
measure: Relationship between GSK1034702 plasma concentrations and safety/tolerability or exploratory PD endpoints with selected pharmacodynamic and safety parameters.
timeFrame: 20 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: