Safety, Tolerability and Pharmacokinetics of GSK1034702 in Healthy Subjects

Single-blind, Randomised, Placebo Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK1034702 in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Disorders
• Intervention / Treatment: Drug: GSK1034702; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7NS
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1; Subjects will be receive GSK1034702 0.5 milligram (mg) following the dose escalation plan	Drug: GSK1034702; Oral or liquid; Drug: Placebo; To match GSK1034702
Other: Cohort 2; Subjects will be receive GSK1034702 5 mg following the dose escalation plan	Drug: GSK1034702; Oral or liquid; Drug: Placebo; To match GSK1034702

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
•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.	20 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of the Bond-Lader Visual Analogue Scale.	20 weeks
Assessment of exploratory PD markers: neuroendocrine markers, e.g. growth hormone.	20 weeks
Relationship between GSK1034702 plasma concentrations and safety/tolerability or exploratory PD endpoints with selected pharmacodynamic and safety parameters.	20 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2008
• Primary Completion (Actual): December 15, 2008
• Study Completion (Actual): December 15, 2008

Study Registration Dates

• First Submitted: August 27, 2008
• First Submitted That Met QC Criteria: August 27, 2008
• First Posted (Estimate): August 28, 2008

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; schizophrenia; M1 receptor agonist; GSK1034702
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders
• Other Study ID Numbers: 110623