Clinical trial NCT00945672: A Multiple Dose Study of PF-04360365 In Patients With Mild to Moderate Alzheimer's Disease
Official title: A PHASE 2 DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING THE SAFETY, TOLERABILITY AND PHARMACOKINETICS/ PHARMACODYNAMICS OF PF-04360365 IN MILD TO MODERATE ALZHEIMER'S DISEASE PATIENTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease amyloid imaging antibody
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-07-24
Enrollment: 36
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether multiple dose administration is safe and well tolerated in patients with mild to moderate Alzheimer's Disease.


Eligibility criteria: Inclusion Criteria:

* Males or females of non childbearing potential, age \> or = 50.
* Diagnosis of probable Alzheimer's disease, consistent with criteria from both:

  * National Institute of Neurological and Communicable Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA).
  * Diagnostic and Statistical Manual of Mental Disorders (DSM IV).
* Mini-mental status exam score of 16-26 inclusive.
* Rosen-Modified Hachinski Ischemia Score of \< or = 4.

Exclusion Criteria:

* Diagnosis or history of other demential or neurodegenerative disorders.
* Diagnosis or history of clinically significant cerebrovascular disease.
* Specific findings on magnetic resonance imaging (MRI); cortical infarct, micro hemorrhage, multiple white matter lacunes, extensive white matter abnormalities.
* History of autoimmune disorders.
* History of allergic or anaphylactic reactions.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Day 1 up to 6 months after last dose of study medication (up to 18 months)
measure: Number of Participants With Change From Baseline in Brain Magnetic Resonance Imaging (MRI) Abnormalities
timeFrame: Baseline up to Month 18
measure: Number of Participants With Gadolinium Use in Brain Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Month 18
measure: Change From Baseline in Amyloid Load at Month 13 Using Positron Emission Tomography (PET) Technique: Cohort M
timeFrame: Baseline, Month 13
measure: Mean Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 0
timeFrame: 0 hour on Day 0 (Day prior to dosing)
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 1
timeFrame: 0 hour (pre-dose) on Day 1
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 1
timeFrame: 0.25 hours post-infusion start on Day 1
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 10: Cohort M
timeFrame: 216 hours post dose on Day 1 (samples taken on Day 10)
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 20: Cohort M
timeFrame: 456 hours post dose on Day 1 (samples taken on Day 20)
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 30: Cohort M
timeFrame: 0 hour (pre-dose) on Day 30
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 30: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 30
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 40: Cohort Q
timeFrame: 936 hours post dose on Day 1 (samples taken on Day 40)
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 50: Cohort Q
timeFrame: 1176 hours post dose on Day 1 (samples taken on Day 50)
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 60: Cohort Q
timeFrame: 1416 hours post-dose on Day 1 (samples taken on Day 60)
measure: Mean Plasma Concentration of PF-04360365 at 0 Hours on Day 60: Cohort M
timeFrame: 0 hour (pre-dose) on Day 60
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 60: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 60
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 90
timeFrame: 0 hour (pre-dose) on Day 90
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 90
timeFrame: 0.25 hours post-infusion start on Day 90
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120: Cohort M
timeFrame: 0 hour (pre-dose) on Day 120
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 120: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 120
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 150: Cohort M
timeFrame: 0 hour (pre-dose) on Day 150
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 150: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 150
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 180
timeFrame: 0 hour (pre-dose) on Day 180
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 180
timeFrame: 0.25 hours post-infusion start on Day 180
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 210: Cohort M
timeFrame: 0 hour (pre-dose) on Day 210
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 210: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 210
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 240: Cohort M
timeFrame: 0 hour (pre-dose) on Day 240
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 240: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 240
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 270
timeFrame: 0 hour (pre-dose) on Day 270
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 270
timeFrame: 0.25 hours post-infusion start on Day 270
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 300: Cohort M
timeFrame: 0 hour (pre-dose) on Day 300
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 300: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 300
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 330: Cohort M
timeFrame: 0 hour (pre-dose) on Day 330
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 330: Cohort M
timeFrame: 0.25 hours post-infusion start on Day 330
measure: Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 360
timeFrame: 0 hour (pre-dose) on Day 360
measure: Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 360
timeFrame: 0.25 hours post-infusion start on Day 360
measure: Mean Plasma Concentration of PF-04360365 at 720 Hours Post-dose on Day 360: Cohort Q
timeFrame: 720 hours post-dose on Day 360 (samples taken on Day 390)
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 390: Cohort M
timeFrame: 0 hour (pre-dose) on Day 390
measure: Mean Plasma Concentration of PF-04360365 at 0 Hours on Day 540: Cohort Q
timeFrame: 0 hours (pre-dose) on Day 540
measure: Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 540: Cohort M
timeFrame: 0 hour (pre-dose) on Day 540
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 0
timeFrame: 0 hour on Day 0 (Day prior to dosing)
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 216 Hours Post-dose on Day 1: Cohort M
timeFrame: 216 hours post-dose on Day 1
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 456 Hours Post-dose on Day 1: Cohort M
timeFrame: 456 hours post-dose on Day 1
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 30: Cohort M
timeFrame: 0 hour (pre-dose) on Day 30
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 936 Hours Post-dose on Day 1: Cohort Q
timeFrame: 936 hours post-dose on Day 1 (Samples taken on Day 40)
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 1176 Hours Post-dose on Day 1: Cohort Q
timeFrame: 1176 hours post-dose on Day 1 (Samples taken on Day 50)
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 1416 Hours Post-dose on Day 1: Cohort Q
timeFrame: 1416 hours post-dose on Day 1 (Samples taken on Day 60)
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 90: Cohort Q
timeFrame: 0 hour (pre-dose) on Day 90
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 180
timeFrame: 0 hour (pre-dose) on Day 180
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 360
timeFrame: 0 hour (pre-dose) on Day 360
Secondary outcomes:
measure: Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Total Score at Months 3, 6, 9, 13 and 18
timeFrame: Baseline, Month 3, 6, 9, 13, 18
measure: Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Month 6, 13 and 18
timeFrame: Baseline, Month 6, 13, 18
measure: Change From Baseline in Mini-Mental State Examination (MMSE) Total Score at Month 13
timeFrame: Baseline, Month 13
measure: Mean Plasma Concentration of Amyloid Beta 1-x (A-beta 1-x)
timeFrame: Cohort M&Q: 0 hour(hr) & 0.25 hrs post dose (pd) on Day (D) 1,90,180,270,360, 0 hr pd on D 60,390; Cohort Q: 936,1176 hrs pd on D1(D 40,50); Cohort M: 216, 456 hrs pd on D1(D 10,20), 0.25 hrs pd on D 60, 0 hr & 0.25 hrs pd on D 30,120,150,210,240,300,330
measure: Mean Plasma Concentration of Amyloid Beta 1-40 (A-beta 1-40)
timeFrame: Cohort M&Q: 0 hr & 0.25 hrs post dose(pd) on Day(D) 1,90,180,270,360, 0 hr pd on D 60,390,540; Cohort Q: 936, 1176 hrs pd on D1(D 40,50); Cohort M: 216, 456 hrs pd on D1(D 10,20), 0.25 hrs pd on D60, 0 hr & 0.25 hrs pd on D 30,120,150,210, 240,300,330
measure: Mean Plasma Concentration of Amyloid Beta 1-42 (A-beta 1-42)
timeFrame: Cohort M&Q: 0 hr & 0.25 hrs post dose(pd) on Day(D) 1,90,180,270,360, 0 hr pd on D 60,390; Cohort Q: 936, 1176 hrs pd on D1(D 40,50); Cohort M: 216, 456 hrs pd on D1(D 10,20), 0.25 hrs pd on D60, 0 hr & 0.25 hrs pd on D 30,120,150,210, 240,300,330
Other outcomes:
measure: Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau) Proteins
timeFrame: Cohort M&Q: Pre dose (0 hr) on Day 0, 0 hr post dose on Day 180, 360; Cohort Q: 936, 1176 hrs post dose on Day 1(Day 40,50), 0 hr post dose on Day 60, 90; Cohort M: 216, 456 hrs post dose on Day 1(Day 10, 20), 0 hr post dose on Day 30
measure: Change From Baseline in Cerebrospinal Fluid (CSF) Protein Concentration at Day 10, 20, 30, 40, 50, 60, 90, 180 and 360
timeFrame: Cohort M&Q: Baseline, 0 hr post dose on Day 180, 360; Cohort Q: 936, 1176 hrs post dose on Day 1(Day 40,50), 0 hr post dose on Day 60, 90; Cohort M: 216, 456 hrs post dose on Day 1(Day 10, 20), 0 hr post dose on Day 30
measure: Change From Baseline in Red Blood Cells (RBCs) and White Blood Cells (WBCs) Concentration in Cerebrospinal Fluid (CSF) at Day 10, 20, 30, 40, 50, 60, 90, 180, 360
timeFrame: Cohort M&Q: Baseline, 0 hr post dose on Day 180, 360; Cohort Q: 936, 1176 hrs post dose on Day 1(Day 40,50), 0 hr post dose on Day 60, 90; Cohort M: 216, 456 hrs post dose on Day 1(Day 10, 20), 0 hr post dose on Day 30
measure: Change From Baseline in Glucose Concentration in Cerebrospinal Fluid (CSF) at Day 10, 20, 30, 40, 50, 60, 90, 180, 360
timeFrame: Cohort M&Q: Baseline, 0 hr post dose on Day 180, 360; Cohort Q: 936, 1176 hrs post dose on Day 1(Day 40,50), 0 hr post dose on Day 60, 90; Cohort M: 216, 456 hrs post dose on Day 1(Day 10, 20), 0 hr post dose on Day 30
measure: Number of Participants With Measurable Serum Anti-Drug Antibody (ADA) Concentration
timeFrame: Day 1 up to Month 18
Locations:
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukhuset, CTC
city: Malmo
country: Sweden
facility: Malmo Sjukhus, Neuropsykiatriska Kliniken
city: Molndal
country: Sweden
facility: Sahlgrenska Universitetssjukhuset, Minnesmottagningen
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: