Trial record 1 of 1 for:    NCT00448890
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Evaluation of Single and Repeat Doses of GSK729327 in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00448890
First received: March 15, 2007
Last updated: October 14, 2010
Last verified: October 2010
  Purpose

GSK729327 is a selective positive allosteric modulator of AMPA-type ionotropic glutamate receptors, exhibiting equivalent potency at all AMPA receptor subtypes. On the basis of preclinical studies it is expected that this compound will improve cognitive measures in schizophrenic patients with acceptable safety. This is a First Time in Human Study (FTIH) to assess the safety, tolerability, pharmacokinetics and preliminary pharmacodynamics of GSK729327 in healthy volunteers. The study will be conducted in 2 parts, with single doses being explored in Part A and multiple doses over 28 days in Part B. Part A will be a single blind, placebo controlled, single oral dose, dose-rising cross-over study in healthy male volunteers. Subjects will be randomized into two cohorts with an alternate panel design. There will be up to nine dosing sessions in total in order to investigate up to 7 different doses. The initial dose will be 0.25 mg and subsequent doses will be determined based on the pharmacokinetic and safety results from the previous dose. Part B will be a randomised, single blind, placebo-controlled, parallel group study of repeat oral dosing of GSK729327. Up to 4 cohorts of 15 (12 subjects receiving active dose and 3 subjects receiving placebo) healthy male and females of (non-childbearing potential) volunteers will be enrolled in Part B.


Condition Intervention Phase
Schizophrenia
Drug: GSK729327
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Single-Blind, Randomised, Placebo-Controlled Two-Part Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Escalating Doses and Repeat Doses of GSK729327 in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability endpoints of AEs; EEG; ECGs; neurological assessments; vital signs and clinical laboratory values.Part A PK parameters of Cmax,AUC,t1/2,Tmax,Ae(0-t).Part B PK parameters of Cmax,Tmax,t1/2,AUC and accumulation ratio. [ Time Frame: throughout the study ]

Secondary Outcome Measures:
  • Pharmacodynamic effects on Bond-Lader,Body Sway and EEG and the relationship of plasma levels of GSK729327 with pharmacodynamic parameters.Part B will also look atcognitive function,Polysomnography and LSEQ. [ Time Frame: throughout the study ]

Enrollment: 79
Study Start Date: November 2006
Study Completion Date: January 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK729327
Dose escalation from 1.0mg to 6 mg.
Drug: GSK729327
Tablets
Other Name: GSK729327
Placebo Comparator: Placebo Drug: Placebo
GSK729327 Matching placebo - Tablets

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male subjects between the ages of 18 and 55 years inclusive.
  • Part B also includes healthy female subjects of non-child bearing potential.
  • A normal ECG, physical examination and laboratory screen.
  • Body weight >50 kg and BMI within the range 18.5-29.9 kg/m2 inclusive.
  • Signed and dated written informed consent prior to admission to the study.

Exclusion Criteria:

  • Abuse of alcohol.
  • A positive pre-study urine drug or alcohol screen.
  • A positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
  • History of DSM-IV alcohol and/or drug abuse or dependence.
  • Consumption of grapefruit juice or grapefruit within 7 days prior to the first dose of study medication until final evaluation.
  • Has received an investigational drug or has participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (which ever is longer) prior to the first dose of study medication.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Use of prescription or non-prescription drugs within 4 weeks prior to the first dose of study medication until final evaluation. Where participation in study would result in donation of blood in excess of 500 ml within a 56 day period.
  • History or presence of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
  • History or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
  • History of cholecystectomy or biliary tract disease.
  • History of regular use of tobacco- or nicotine-containing products within 6 months of the start of a study.
  • An unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation if the woman could become pregnant from the time of the first dose of study medication until 90 days following administration of the last dose of study medication.QTc interval > 450 ms. Or an ECG that is not suitable for QT measurements.
  • History of long QT syndrome (personal or family) or other cardiac conduction disorder, or other clinically significant cardiac disease.
  • The subject has a history of myocardial infarction .The subject has a resting pulse rate <55 or >100 bpm OR a systolic blood pressure >140 or <100 OR a diastolic blood pressure >90 or <60.Current or past history of symptomatic orthostatic hypotension. The subject has any laboratory abnormality that in the investigator's judgment is considered to be clinically significant (even if not outside of specified ranges).History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).History or presence of psychiatric disease.
  • History of suicidal attempts or behavior. Subjects who cannot complete the neuropsychological test battery despite having undergone the training sessions.
  • Subject has a history of sleep problems in the last 3 months.
  • The subject has clinically significant abnormalities in haematology, blood chemistry, ECG, or physical examination not resolved by the screening visit. Abnormal response to photic stimulation EEG. Abnormal prolactin or TSH or free T4 or free T3 at screening/baseline.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00448890

Locations
Germany
GSK Investigational Site
Berlin, Germany, 14050
United Kingdom
GSK Investigational Site
London, United Kingdom, SE1 1YR
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00448890     History of Changes
Other Study ID Numbers: AM1107296
Study First Received: March 15, 2007
Last Updated: October 14, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
AMPA positive modulator, healthy volunteers

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on October 01, 2014