Clinical Program

PBT2


PBT2 has exhibited superior performance in a variety of laboratory and animal screening tests designed to assess the ability of the compound to interfere with the toxic mechanisms of AD & HD. The positive effects on basic function delivered by the actions of PBT2 include:

(i) Anti Abeta and mutant huntingtin (mHtt) effects:
    • Reduces Abeta Aggregation
    • Promotes Dissolution of Abeta oligomers 
    • Prevents toxicity of Abeta oligomers (preventing binding to NMDA receptors)
    • Promotes Abeta Degradation and Clearance
    • Redistributes Abeta-Sequestered Metals back into neurons and other cells
    • Reduces mHtt Aggregation

(ii) Neuroprotective and neurotrophic effects
    • Redistributes metals into neurons and modulates intracellular signalling
       pathways
    • Reduces potential for glutamate excitotoxicity
    • Restores Synaptic Plasticity (LTP and Spine Density) ie promotes neuronal 
       regrowth
    • Prevents free radical production (silences redox activity or redox active
       metals)
    • Reduces tau hyperphosphorylation
    • Reduces brain striatal tissue degeneration

These findings lead to clinical development of the compound in humans.

 Phase
 Population
 Treatment
 Status & Key Points
 IHealthy males aged 18-50 years.PBT2-001
Single Dose 8-arm Study: Up to 800 mg PBT2 versus placebo (‘sugar pill’).

Status: Completed.

Objective: To determine the safety, tolerability and pharmacokinetics of single and multiple oral doses in healthy volunteers.

Outcome: PBT2 was well tolerated as a single dose in young male volunteers and up to 7 days of treatment in older healthy volunteers.

 IHealthy males/females aged 45-75 years.Multiple Dose 5-arm study: Up to 800 mg PBT2 versus placebo once daily for 7 days.
 IIaMild Alzheimer’s Disease in males/females aged over 55 years. PBT2-201
3-arm study: 50 mg and 250 mg PBT2 versus placebo once daily for 12 weeks.

Status: Completed.

Primary Objective:
• To assess the safety and tolerability of PBT2 in patients suffering from mild Alzheimer's Disease (AD).

Secondary Objectives:
• To assess the effect of PBT2 on biomarkers associated with AD.
• To determine the impact of PBT2 on cognition.

Outcomes:
• PBT2 was safe and well tolerated in patients with mild AD.
• PBT2 reduced Abeta levels in the CSF of patients on the 250mg dose.
• Cognitive Executive Function as measured by the NTB (Neuropsychological Test Battery) was significantly improved for patients on the 250mg dose.

References:
Lannfelt et al. Lancet Neurology (2008) vol.7, pp 779-86
Lannfelt et al. Erratum: Lancet Neurology (2009) vol.8, pp 981

 IIProdromal or Mild Alzheimer's Disease in males/females over 55 years.PBT2-204
2 arm study: 250mg PBT2 versus placebo once daily for 52 weeks.

Status: Enrolment Complete.

Primary Objective:
• To evaluate brain amyloid levels.

Secondary Objectives:
To evaluate the effect of PBT2 on; 
• Safety and tolerability.
• Brain metabolic activity.
• Brain volumes.
• Cognition.
• Functional abilities.   

 

 IIEarly to Mild Stage Huntington's Disease in males/femalesPBT2-203
3 arm study: 100mg and 250 mg PBT2 versus placebo once daily for 26 weeks.

Status: Enrolment Complete.

Primary Objective:
• To evaluate safety and tolerability in patients with HD.

Secondary Objectives:
To evaluate the effect of PBT2 on;
• Cognition.
• Motor Function.
• Behaviour.
• Funcional Abilities.
• Global Function.
• Biomarkers.
• Brain Volume and function.
• Pharmacokinetics. 


For further information on the clinical trial process please refer to the ClinicalTrials.gov website.
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