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A Long-Term Safety And Tolerability Study Of Bapineuzumab In Alzheimer Disease Patients

This study has been terminated.
(The study was terminated on August 6, 2012, because 2 large Phase 3 studies showed no clinical benefit. This decision was not based on any new safety concerns.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00996918
First received: October 14, 2009
Last updated: November 12, 2013
Last verified: November 2013
Results First Received: November 12, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Interventions: Drug: Bapineuzumab 0.5 mg/kg
Drug: Bapineuzumab 1.0 m/kg

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This extension study was conducted at 91 centers in 17 countries. The study was terminated early by the sponsor on 06 August 2012. Participants who had not completed the final follow-up visit prior to 06 August 2012 were asked to complete an early termination visit.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants who had completed the base study protocol 3133K1-3000 were allowed to participate in this extension study. Participants who developed vasogenic edema during study 3133K1-3000 were considered for study 3133K1-3002 participation if the abnormality was resolved and the participant met criteria to resume the investigational product.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 Milligram/Kilogram(mg/kg) Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 2.0 mg/kg/ Bapineuzumab 1.0 mg/kg Participants originally randomized to 2.0 mg/kg bapineuzumab were reassigned to the 1.0 mg/kg dose level after discontinuation of 2.0 mg/kg dose level in the base study and continued the 1.0 mg/kg dose in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Participant Flow:   Overall Study
    Placebo/Bapineuzumab 0.5 Milligram/Kilogram(mg/kg)   Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg   Placebo/Bapineuzumab 1.0 mg/kg   Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg   Bapineuzumab 2.0 mg/kg/ Bapineuzumab 1.0 mg/kg
STARTED   39   66   37   56   4 
Treated   39   66   37   56   4 
COMPLETED   0   0   0   0   0 
NOT COMPLETED   39   66   37   56   4 
Lack of Efficacy                1                1                2                2                0 
Adverse Event                2                5                2                6                0 
Withdrawal by Subject                1                4                3                3                2 
Physician Decision                1                0                0                0                0 
Discontinuation of Study by Sponsor                31                54                30                45                2 
Loss of Caregiver                0                1                0                0                0 
Not Specified                3                1                0                0                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 2.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants originally randomized to 2.0 mg/kg bapineuzumab were reassigned to the 1.0 mg/kg dose level after discontinuation of 2.0 mg/kg dose level in the base study and continued the 1.0 mg/kg dose in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Total Total of all reporting groups

Baseline Measures
   Placebo/Bapineuzumab 0.5 mg/kg   Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg   Placebo/Bapineuzumab 1.0 mg/kg   Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg   Bapineuzumab 2.0 mg/kg/Bapineuzumab 1.0 mg/kg   Total 
Overall Participants Analyzed 
[Units: Participants]
 38   62   33   53   4   190 
Age 
[Units: Years]
Mean (Standard Deviation)
 68.9  (9.70)   71.9  (8.83)   68.8  (8.59)   70.6  (9.13)   71.3  (10.63)   70.4  (9.08) 
Age, Customized 
[Units: Number of participants]
           
< 65   17   15   12   17   1   62 
>= 65   21   47   21   36   3   128 
Gender 
[Units: Number of participants]
           
Female   13   28   14   19   3   77 
Male   25   34   19   34   1   113 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Reporting a Serious Adverse Event.   [ Time Frame: Up to Week 195 ]

2.  Secondary:   Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: Weeks 13, 26, 39, 52 and 78 ]

3.  Secondary:   Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: Weeks 13, 26, 39, 52 and 78 ]

4.  Secondary:   Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: Weeks 13, 26, 39, 52 and 78 ]

5.  Secondary:   Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78   [ Time Frame: Weeks 13, 26, 39, 52 and 78 ]

6.  Secondary:   Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.   [ Time Frame: Weeks 26, 52 and 78 ]

7.  Secondary:   Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.   [ Time Frame: Weeks 26, 52 and 78 ]

8.  Secondary:   Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.   [ Time Frame: Weeks 6, 19, 32, 45 and 78 ]

9.  Secondary:   Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.   [ Time Frame: Weeks 6, 19, 32, 45 and 78 ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame 2.6 years
Additional Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 2.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants originally randomized to 2.0 mg/kg bapineuzumab were reassigned to the 1.0 mg/kg dose level after discontinuation of 2.0 mg/kg dose level in the base study and continued the 1.0 mg/kg dose in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Other Adverse Events
    Placebo/Bapineuzumab 0.5 mg/kg   Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg   Placebo/Bapineuzumab 1.0 mg/kg   Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg   Bapineuzumab 2.0 mg/kg/Bapineuzumab 1.0 mg/kg
Total, other (not including serious) adverse events           
# participants affected / at risk   18/39 (46.15%)   21/66 (31.82%)   15/37 (40.54%)   15/56 (26.79%)   3/4 (75.00%) 
Blood and lymphatic system disorders           
Anaemia * 1           
# participants affected / at risk   2/39 (5.13%)   1/66 (1.52%)   0/37 (0.00%)   0/56 (0.00%)   0/4 (0.00%) 
# events   2   1   0   0   0 
Eye disorders           
Arteriosclerotic retinopathy * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   0/37 (0.00%)   0/56 (0.00%)   1/4 (25.00%) 
# events   0   0   0   0   1 
Cataract * 1           
# participants affected / at risk   0/39 (0.00%)   2/66 (3.03%)   0/37 (0.00%)   0/56 (0.00%)   1/4 (25.00%) 
# events   0   3   0   0   1 
Gastrointestinal disorders           
Nausea * 1           
# participants affected / at risk   2/39 (5.13%)   0/66 (0.00%)   0/37 (0.00%)   0/56 (0.00%)   0/4 (0.00%) 
# events   2   0   0   0   0 
General disorders           
Gait disturbance * 1           
# participants affected / at risk   3/39 (7.69%)   0/66 (0.00%)   1/37 (2.70%)   0/56 (0.00%)   0/4 (0.00%) 
# events   3   0   1   0   0 
Infections and infestations           
Cystitis * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   0/37 (0.00%)   1/56 (1.79%)   1/4 (25.00%) 
# events   0   0   0   1   1 
Gastroenteritis * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   3/37 (8.11%)   0/56 (0.00%)   0/4 (0.00%) 
# events   0   0   3   0   0 
Nasopharyngitis * 1           
# participants affected / at risk   3/39 (7.69%)   1/66 (1.52%)   1/37 (2.70%)   2/56 (3.57%)   0/4 (0.00%) 
# events   3   1   2   2   0 
Urinary tract infection * 1           
# participants affected / at risk   2/39 (5.13%)   7/66 (10.61%)   1/37 (2.70%)   0/56 (0.00%)   0/4 (0.00%) 
# events   2   7   2   0   0 
Injury, poisoning and procedural complications           
Fall * 1           
# participants affected / at risk   0/39 (0.00%)   3/66 (4.55%)   2/37 (5.41%)   3/56 (5.36%)   0/4 (0.00%) 
# events   0   6   2   3   0 
Metabolism and nutrition disorders           
Folate deficiency * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   0/37 (0.00%)   0/56 (0.00%)   1/4 (25.00%) 
# events   0   0   0   0   1 
Hypercholesterolaemia * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   0/37 (0.00%)   0/56 (0.00%)   1/4 (25.00%) 
# events   0   0   0   0   1 
Nervous system disorders           
Cerebral microhaemorrhage * 1           
# participants affected / at risk   0/39 (0.00%)   1/66 (1.52%)   0/37 (0.00%)   3/56 (5.36%)   1/4 (25.00%) 
# events   0   2   0   3   1 
Cognitive disorder * 1           
# participants affected / at risk   1/39 (2.56%)   2/66 (3.03%)   2/37 (5.41%)   3/56 (5.36%)   0/4 (0.00%) 
# events   1   3   2   3   0 
Dizziness * 1           
# participants affected / at risk   1/39 (2.56%)   4/66 (6.06%)   0/37 (0.00%)   0/56 (0.00%)   0/4 (0.00%) 
# events   1   4   0   0   0 
Headache * 1           
# participants affected / at risk   1/39 (2.56%)   1/66 (1.52%)   3/37 (8.11%)   2/56 (3.57%)   0/4 (0.00%) 
# events   1   1   4   2   0 
Presyncope * 1           
# participants affected / at risk   0/39 (0.00%)   1/66 (1.52%)   2/37 (5.41%)   0/56 (0.00%)   0/4 (0.00%) 
# events   0   1   2   0   0 
Vasogenic cerebral oedema * 1           
# participants affected / at risk   2/39 (5.13%)   2/66 (3.03%)   5/37 (13.51%)   3/56 (5.36%)   0/4 (0.00%) 
# events   2   2   5   3   0 
Psychiatric disorders           
Aggression * 1           
# participants affected / at risk   2/39 (5.13%)   0/66 (0.00%)   0/37 (0.00%)   0/56 (0.00%)   0/4 (0.00%) 
# events   3   0   0   0   0 
Delusion * 1           
# participants affected / at risk   3/39 (7.69%)   3/66 (4.55%)   0/37 (0.00%)   0/56 (0.00%)   0/4 (0.00%) 
# events   3   3   0   0   0 
Depression * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   2/37 (5.41%)   0/56 (0.00%)   0/4 (0.00%) 
# events   0   0   3   0   0 
Reproductive system and breast disorders           
Benign prostatic hyperplasia * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   1/37 (2.70%)   0/56 (0.00%)   1/4 (25.00%) 
# events   0   0   1   0   1 
Respiratory, thoracic and mediastinal disorders           
Cough * 1           
# participants affected / at risk   2/39 (5.13%)   0/66 (0.00%)   0/37 (0.00%)   2/56 (3.57%)   0/4 (0.00%) 
# events   3   0   0   2   0 
Skin and subcutaneous tissue disorders           
Rash erythematous * 1           
# participants affected / at risk   0/39 (0.00%)   0/66 (0.00%)   0/37 (0.00%)   0/56 (0.00%)   1/4 (25.00%) 
# events   0   0   0   0   1 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 15.0



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Bapineuzumab program was discontinued prematurely. Efficacy results obtained after Week 78 are not presented due to the very small number of participants after this time point.


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