Modulation of Abeta Levels by GSK933776 in Alzheimer's Disease Patient

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01424436
First received: August 4, 2011
Last updated: September 5, 2013
Last verified: May 2012

August 4, 2011
September 5, 2013
May 2010
December 2011   (final data collection date for primary outcome measure)
The temporal changes of amyloid beta levels in CSF after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment [ Time Frame: 22 hours ] [ Designated as safety issue: No ]
To compare the changes of amyloid beta levels between the baseline (9 hours) and after single dose of GSK933776 iv administration of 13 hours
Same as current
Complete list of historical versions of study NCT01424436 on ClinicalTrials.gov Archive Site
  • The temporal changes of total and free amyloid beta levels in plasma after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment [ Time Frame: Two months ] [ Designated as safety issue: No ]
  • The temporal changes of Tau and phosphor Tau - 181 levels in CSF after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment [ Time Frame: 22 hours ] [ Designated as safety issue: No ]
  • Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at multiple time points with various intervals. [ Time Frame: three months ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability after single dose of GSK933776 administration. [ Time Frame: three months ] [ Designated as safety issue: No ]
    The safety and tolerability measures are performed at screening, dosing day and follow up. The assessments included: • Adverse event reporting and safety laboratory data. • CNS Safety: MRI and MMSE. • CVS safety: ECG and vital signs. •Anti-GSK933776 antibodies.
  • The temporal changes of total and free amyloid beta levels in plasma after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment [ Time Frame: Two months ] [ Designated as safety issue: No ]
  • The temporal changes of Tau and phosphor Tau - 181 levels in CSF after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment [ Time Frame: 22 hours ] [ Designated as safety issue: No ]
  • Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at mutiple time points with various intervals. [ Time Frame: three months ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability after single dose of GSK933776 administration. [ Time Frame: three months ] [ Designated as safety issue: No ]
    The safety and tolerability measures are perfored at screening, dosing day and follow up. The assessments included: • Adverse event reporting and safety laboratory data. • CNS Safety: MRI and MMSE. • CVS safety: ECG and vital signs. •Anti-GSK933776 antibodies.
Not Provided
Not Provided
 
Modulation of Abeta Levels by GSK933776 in Alzheimer's Disease Patient
Modulation of Beta-amyloid Levels in CSF and Plasma by GSK933776 in Patients With Mild Alzheimer's Disease or Mild Cognitive Impairment

Modulation of beta-amyloid levels in CSF and plasma by GSK933776 in patients with mild Alzheimer's disease or mild cognitive impairment

This is a phase I, an open label, single dose and parallel group study to assess short term pharmacodynamics and safety of GSK933776. The effect on the beta amyloid levels will be assessed in early (MCI) and mild Alzheimer's disease (AD) patients after a single dose of GSK933776 by i.v. administration.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Alzheimer's Disease
  • Biological: GSK933776
    1mg/kg dose group
  • Biological: GSK933776
    3mg/kg dose group
  • Biological: GSK933776
    6mg/kg dose group
  • Experimental: GSK933776 1mg/kg
    single dose
    Intervention: Biological: GSK933776
  • Experimental: GSK933776 0.1 or 3mg/kg
    single dose
    Intervention: Biological: GSK933776
  • Experimental: GSK933776 3 or 6mg/kg
    single dose
    Intervention: Biological: GSK933776
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
19
December 2011
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Probable mild Alzheimer's disease (MMSE 20-26) or mild cognitive impairment
  • Increase in total tau or p-tau in CSF
  • Decrease in amyloid beta in CSF
  • Stable dose of cholinesterase inhibitors, memantine or selegine or no treatment
  • Body weight less than 120 kg
  • Willingness to comply with contraceptive methods if self or partner is of child-bearing potential

Exclusion Criteria:

  • Any other cause of dementia
  • Other significant neurologic or psychiatric illness
  • Hachinski Ischemia Score >4
  • More than 3 microbleeds on MRI
  • Type 2 diabetes not controlled by diet
  • Risk of cerebrovascular disease, cerebral haemorrhage or stroke
  • History of systemic autoimmune disease
  • Use of platelet anti-aggregates or anti-coagulants (Aspirin up to 325 mg/day is allowable)
  • Use of chronic corticosteroids
  • Uncontrolled hypertension in spite of antihypertensive medications
  • Renal or hepatic insufficiency or clinically significant anaemia
  • In nursing home care
  • Contraindications to lumbar puncture or MRI
  • Prior participation in therapeutic studies only after adequate wash-out period
Both
55 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Sweden
 
NCT01424436
113043
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP