NCT00722046

Multiple IV Dose Study Of PF-04360365 In Patients With Mild To Moderate Alzheimer's Disease

Completed Phase 2 Results posted Last updated 7 November 2022

What this trial tests

Phase 2 trial testing PF-04360365 0.1 mg/kg in Alzheimer's Disease in 198 participants. Completed in 16 August 2011.

Timeline

5 December 2008

Primary endpoint
16 August 2011

16 August 2011

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	198
Start date	5 December 2008
Primary completion	16 August 2011
Estimated completion	16 August 2011
Sites	42 locations across Belgium, United Kingdom, South Korea, Canada, Australia, United States

Drugs / interventions tested

• PF-04360365 0.1 mg/kg — full drug profile →
• PF-04360365 0.5 mg/kg — full drug profile →
• PF-04360365 1 mg/kg — full drug profile →
• Placebo
• PF-04360365 3 mg/kg — full drug profile →
• PF-04360365 8.5 mg/kg — full drug profile →

Conditions studied

• Alzheimer's Disease — all drugs for Alzheimer's Disease →

Sponsor

Pfizer — full company profile →

Who can join

50 and older, any sex, with Alzheimer's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Primary · Day 1 up to 6 months after last dose of study medication, assessed up to Month 24

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study medication and up to 6 months after last dose that were absent before treatment or worsened relative to pre-treatment stat

AEs

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	24
PF-04360365 0.5 mg/kg (Part A)	24
PF-04360365 1.0 mg/kg (Part A)	24
Placebo (Part A)	24
PF-04360365 3.0 mg/kg (Part B)	27
PF-04360365 8.5 mg/kg (Part B)	28
Placebo (Part B)	32

SAEs

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	7
PF-04360365 0.5 mg/kg (Part A)	8
PF-04360365 1.0 mg/kg (Part A)	7
Placebo (Part A)	3
PF-04360365 3.0 mg/kg (Part B)	7
PF-04360365 8.5 mg/kg (Part B)	10
Placebo (Part B)	3

Number of Participants With Change From Baseline in Brain Magnetic Resonance Imaging (MRI) Abnormalities Primary · Baseline up to Month 24

Number of participants with new clinical findings not evident on the baseline scans, such as brain edema, hemorrhage, encephalitis and other pathology (cerebral/meningeal enhancement, parenchymal hematoma, subarachnoid hemorrhage, subdural hematoma, cortical infarcts, subcortical grey matter infarcts, white matter infarcts and white matter hyperintensities) were assessed from structural MRI. Participants with brain abnormality other than those listed above, assessed using MRI scan, were reported under other abnormality. Baseline was defined as the last assessment prior to the first study drug

Cerebral Edema

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0
PF-04360365 0.5 mg/kg (Part A)	1
PF-04360365 1.0 mg/kg (Part A)	0
Placebo (Part A)	0
PF-04360365 3.0 mg/kg (Part B)	0
PF-04360365 8.5 mg/kg (Part B)	0
Placebo (Part B)	0

Cerebral/Meningeal Enhancement

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0
PF-04360365 0.5 mg/kg (Part A)	1
PF-04360365 1.0 mg/kg (Part A)	0
Placebo (Part A)	0
PF-04360365 3.0 mg/kg (Part B)	0
PF-04360365 8.5 mg/kg (Part B)	0
Placebo (Part B)	0

Micro Hemorrhage

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	4
PF-04360365 0.5 mg/kg (Part A)	7
PF-04360365 1.0 mg/kg (Part A)	2
Placebo (Part A)	6
PF-04360365 3.0 mg/kg (Part B)	3
PF-04360365 8.5 mg/kg (Part B)	6
Placebo (Part B)	6

Subdural Hematoma

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0
PF-04360365 0.5 mg/kg (Part A)	1
PF-04360365 1.0 mg/kg (Part A)	0
Placebo (Part A)	0
PF-04360365 3.0 mg/kg (Part B)	0
PF-04360365 8.5 mg/kg (Part B)	0
Placebo (Part B)	0

Cortical Infarcts

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	1
PF-04360365 0.5 mg/kg (Part A)	0
PF-04360365 1.0 mg/kg (Part A)	2
Placebo (Part A)	0
PF-04360365 3.0 mg/kg (Part B)	0
PF-04360365 8.5 mg/kg (Part B)	1
Placebo (Part B)	0

Subcortical Grey Matter Infarcts

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0
PF-04360365 0.5 mg/kg (Part A)	0
PF-04360365 1.0 mg/kg (Part A)	0
Placebo (Part A)	0
PF-04360365 3.0 mg/kg (Part B)	1
PF-04360365 8.5 mg/kg (Part B)	1
Placebo (Part B)	0

White Matter Infarcts

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0
PF-04360365 0.5 mg/kg (Part A)	1
PF-04360365 1.0 mg/kg (Part A)	0
Placebo (Part A)	0
PF-04360365 3.0 mg/kg (Part B)	0
PF-04360365 8.5 mg/kg (Part B)	0
Placebo (Part B)	2

White Matter Hyper Intensities

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0
PF-04360365 0.5 mg/kg (Part A)	3
PF-04360365 1.0 mg/kg (Part A)	2
Placebo (Part A)	2
PF-04360365 3.0 mg/kg (Part B)	4
PF-04360365 8.5 mg/kg (Part B)	0
Placebo (Part B)	2

Number of Participants With Gadolinium Use in Brain Magnetic Resonance Imaging (MRI) Primary · Baseline up to Month 24

Brain MRI included gadolinium contrast if investigator determined this was necessary for participant care either based on clinical signs or the non-contrast MRI. This decision was made by the investigator on the basis of change in the clinical examination or in response to a possible abnormality seen on the non-contrast brain MRI. Baseline was defined as the last assessment prior to the first study drug infusion.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	3
PF-04360365 0.5 mg/kg (Part A)	1
PF-04360365 1.0 mg/kg (Part A)	2
Placebo (Part A)	1
PF-04360365 3.0 mg/kg (Part B)	1
PF-04360365 8.5 mg/kg (Part B)	2
Placebo (Part B)	3

Mean Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 0 Primary · 0 Hour on Day 0

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0.00	± 0.00
PF-04360365 0.5 mg/kg (Part A)	0.00	± 0.00
PF-04360365 1.0 mg/kg (Part A)	0.00	± 0.00
PF-04360365 3.0 mg/kg (Part B)	0.00	± 0.00
PF-04360365 8.5 mg/kg (Part B)	0.00	± 0.00

Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 1 Primary · 0 Hour (pre-dose) on Day 1

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0.00	± 0.00
PF-04360365 0.5 mg/kg (Part A)	0.00	± 0.00
PF-04360365 1.0 mg/kg (Part A)	14.25	± 69.81
PF-04360365 3.0 mg/kg (Part B)	0.00	± 0.00
PF-04360365 8.5 mg/kg (Part B)	38.10	± 208.68

Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 1 Primary · 2 Hours on Day 1

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	1731.36	± 605.07
PF-04360365 0.5 mg/kg (Part A)	10051.85	± 1857.36
PF-04360365 1.0 mg/kg (Part A)	21972.09	± 6582.50
PF-04360365 3.0 mg/kg (Part B)	65832.36	± 23334.31
PF-04360365 8.5 mg/kg (Part B)	187953.19	± 36763.80

Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 60 Primary · 0 Hour (pre-dose) on Day 60

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	33.96	± 82.22
PF-04360365 0.5 mg/kg (Part A)	792.80	± 217.31
PF-04360365 1.0 mg/kg (Part A)	1747.04	± 311.05
PF-04360365 3.0 mg/kg (Part B)	6715.34	± 3797.08
PF-04360365 8.5 mg/kg (Part B)	30517.76	± 34018.99

Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 60 Primary · 2 Hours on Day 60

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	2018.13	± 402.12
PF-04360365 0.5 mg/kg (Part A)	11372.46	± 2730.02
PF-04360365 1.0 mg/kg (Part A)	23100.33	± 5598.52
PF-04360365 3.0 mg/kg (Part B)	81464.62	± 25466.75
PF-04360365 8.5 mg/kg (Part B)	209962.13	± 64637.17

Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 90 Primary · Day 90

Only participants received PF-04360365 were analyzed for this outcome measure.

CSF

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	0.00	± 0.00
PF-04360365 0.5 mg/kg (Part A)	0.00	± 0.00
PF-04360365 1.0 mg/kg (Part A)	6.36	± 14.22
PF-04360365 3.0 mg/kg (Part B)	43.44	± 17.76
PF-04360365 8.5 mg/kg (Part B)	157.40	± 85.17

Plasma

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	286.20	± 133.25
PF-04360365 0.5 mg/kg (Part A)	2074.48	± 558.85
PF-04360365 1.0 mg/kg (Part A)	4277.88	± 1073.25
PF-04360365 3.0 mg/kg (Part B)	16733.03	± 5624.57
PF-04360365 8.5 mg/kg (Part B)	49141.68	± 11941.83

Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120 Primary · 0 Hour (pre-dose) on Day 120

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	106.08	± 116.00
PF-04360365 0.5 mg/kg (Part A)	1259.68	± 360.11
PF-04360365 1.0 mg/kg (Part A)	2573.64	± 622.86
PF-04360365 3.0 mg/kg (Part B)	8781.20	± 3267.52
PF-04360365 8.5 mg/kg (Part B)	31916.04	± 24631.87

Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 120 Primary · 2 Hours on Day 120

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	2083.14	± 549.16
PF-04360365 0.5 mg/kg (Part A)	12229.60	± 2813.13
PF-04360365 1.0 mg/kg (Part A)	25263.43	± 6395.62
PF-04360365 3.0 mg/kg (Part B)	69437.52	± 19262.08
PF-04360365 8.5 mg/kg (Part B)	191019.54	± 65338.19

Mean Plasma Concentration of PF-04360365 on Day 150 Primary · Day 150

Only participants received PF-04360365 were analyzed for this outcome measure.

Group	Value	95% CI
PF-04360365 0.1 mg/kg (Part A)	344.17	± 157.08
PF-04360365 0.5 mg/kg (Part A)	2512.36	± 804.43
PF-04360365 1.0 mg/kg (Part A)	4673.32	± 932.48
PF-04360365 3.0 mg/kg (Part B)	17636.10	± 6440.44
PF-04360365 8.5 mg/kg (Part B)	53918.22	± 15265.59

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-04360365 0.1 mg/kg (Part A)

Serious: 7/25 (28%)

Deaths: —

PF-04360365 0.5 mg/kg (Part A)

Serious: 8/25 (32%)

Deaths: —

PF-04360365 1.0 mg/kg (Part A)

Serious: 7/25 (28%)

Deaths: —

Placebo (Part A)

Serious: 3/24 (13%)

Deaths: —

PF-04360365 3.0 mg/kg (Part B)

Serious: 7/32 (22%)

Deaths: —

PF-04360365 8.5 mg/kg (Part B)

Serious: 10/31 (32%)

Deaths: —

Placebo (Part B)

Serious: 3/32 (9%)

Deaths: —

Serious adverse events (71 terms)

Reaction	System	PF-04360365 0.1 mg/kg (Par…	PF-04360365 0.5 mg/kg (Par…	PF-04360365 1.0 mg/kg (Par…	Placebo (Part A)	PF-04360365 3.0 mg/kg (Par…	PF-04360365 8.5 mg/kg (Par…	Placebo (Part B)
Myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Delirium	Psychiatric disorders	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Acute coronary syndrome	Cardiac disorders	—	—	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—
Bradycardia	Cardiac disorders	—	—	—	—	—	—	—
Cardiogenic shock	Cardiac disorders	—	—	—	—	—	—	—
Coronary artery stenosis	Cardiac disorders	—	—	—	—	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—	—	—	—	—
Sick sinus syndrome	Cardiac disorders	—	—	—	—	—	—	—
Vertigo positional	Ear and labyrinth disorders	—	—	—	—	—	—	—
Colonic polyp	Gastrointestinal disorders	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—	—	—	—	—
Periodontitis	Gastrointestinal disorders	—	—	—	—	—	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—
Chest discomfort	General disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—

Other adverse events (424 terms — click to expand)

Reaction	System	PF-04360365 0.1 mg/kg (Par…	PF-04360365 0.5 mg/kg (Par…	PF-04360365 1.0 mg/kg (Par…	Placebo (Part A)	PF-04360365 3.0 mg/kg (Par…	PF-04360365 8.5 mg/kg (Par…	Placebo (Part B)
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Cerebral microhaemorrhage	Nervous system disorders	—	—	—	—	—	—	—
Confusional state	Psychiatric disorders	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—
Laceration	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—
Weight increased	Investigations	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Agitation	Psychiatric disorders	—	—	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—
Benign prostatic hyperplasia	Reproductive system and breast disorders	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Faecal incontinence	Gastrointestinal disorders	—	—	—	—	—	—	—
Irritability	General disorders	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—
Joint sprain	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—	—	—	—
Sinus bradycardia	Cardiac disorders	—	—	—	—	—	—	—
Ventricular extrasystoles	Cardiac disorders	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Myocardial infarction, Prostate cancer, Delirium, Anaemia, Acute coronary syndrome, Acute myocardial infarction, Angina pectoris, Atrial fibrillation.

Data from ClinicalTrials.gov NCT00722046 adverse events section.

Sponsor's own description

Purpose of the study is to determine whether multiple dose administration of PF-04360365 is safe and well tolerated in patient with mild to moderate Alzheimer's disease.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Alzheimer's disease and the amyloid cascade hypothesis: a critical review.
   Reitz C. · · 2012 · cited 194× · PMID 22506132 · DOI 10.1155/2012/369808
2. Passive immunotherapies targeting Aβ and tau in Alzheimer's disease.
   Plotkin SS, Cashman NR. · · 2020 · cited 106× · PMID 32682954 · DOI 10.1016/j.nbd.2020.105010
3. Current Alzheimer's disease clinical trials: methods and placebo outcomes.
   Schneider LS, Sano M. · · 2009 · cited 101× · PMID 19751918 · DOI 10.1016/j.jalz.2009.07.038
4. Drug Development for Alzheimer's Disease: Microglia Induced Neuroinflammation as a Target?
   Dong Y, Li X, Cheng J, Hou L. · · 2019 · cited 97× · PMID 30696107 · DOI 10.3390/ijms20030558
5. The Neurovascular Unit Dysfunction in Alzheimer's Disease.
   Soto-Rojas LO, Pacheco-Herrero M, Martínez-Gómez PA, Campa-Córdoba BB, et al · · 2021 · cited 95× · PMID 33670754 · DOI 10.3390/ijms22042022
6. Safety and Efficacy of Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials.
   Lacorte E, Ancidoni A, Zaccaria V, Remoli G, et al · · 2022 · cited 78× · PMID 35275549 · DOI 10.3233/jad-220046
7. Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer's Disease.
   Toniolo S, Sen A, Husain M. · · 2020 · cited 74× · PMID 33297460 · DOI 10.3390/ijms21239318
8. Bapineuzumab.
   Kerchner GA, Boxer AL. · · 2010 · cited 63× · PMID 20497044 · DOI 10.1517/14712598.2010.493872