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Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Agitation and Aggression in Alzheimer's Disease (SERENE)

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ClinicalTrials.gov Identifier: NCT02992132
Recruitment Status : Terminated
First Posted : December 14, 2016
Results First Posted : March 28, 2019
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
ACADIA Pharmaceuticals Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Agitation and Aggression in Alzheimer's Disease
Interventions Drug: Pimavanserin 34 mg
Drug: Pimavanserin 20 mg
Other: Placebo
Enrollment 111
Recruitment Details The study was planned to be conducted in approximately 432 subjects. For business reasons, and not related to safety, recruitment of subjects was stopped after 111 subjects were randomized. The last subject was randomized on 2 Nov 2017.
Pre-assignment Details The screening visit was followed by a 2- to 4-week screening period, including wash-out of antipsychotic agents which were prohibited during the Treatment period (exception: protocol specified agents). Subjects had to be on stable doses of permitted medications for >=4 weeks before Baseline (>=12 weeks for cholinesterase inhibitors and memantine).
Arm/Group Title Placebo Pimavanserin 20 mg Pimavanserin 34 mg
Hide Arm/Group Description

Placebo, taken as two tablets, once daily by mouth

Placebo: Placebo, taken as two tablets, once daily by mouth

Drug- pimavanserin tartrate, 20 mg, taken as two 10 mg tablets, once daily by mouth

Pimavanserin 20 mg: Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth

Drug- pimavanserin tartrate, 34 mg, taken as two 17 mg tablets, once daily by mouth

Pimavanserin 34 mg: Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth

Period Title: Overall Study
Started 40 35 36
Completed 27 27 29
Not Completed 13 8 7
Reason Not Completed
Adverse Event             4             1             3
Lack of Efficacy             2             0             0
Non-compliance with study drug             2             0             0
Progressive disease             1             0             0
Protocol Violation             2             2             0
Caregiver withdrew consent             2             3             2
Withdrawal by Subject             0             2             1
Physician Decision             0             0             1
Arm/Group Title Placebo Pimavanserin 20 mg Pimavanserin 34 mg Total
Hide Arm/Group Description

Placebo, taken as two tablets, once daily by mouth

Placebo: Placebo, taken as two tablets, once daily by mouth

Drug- pimavanserin tartrate, 20 mg, taken as two 10 mg tablets, once daily by mouth

Pimavanserin 20 mg: Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth

Drug- pimavanserin tartrate, 34 mg, taken as two 17 mg tablets, once daily by mouth

Pimavanserin 34 mg: Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth

Total of all reporting groups
Overall Number of Baseline Participants 40 35 36 111
Hide Baseline Analysis Population Description
All patients randomized
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 35 participants 36 participants 111 participants
78.9  (7.58) 76.5  (8.74) 75.0  (7.90) 76.8  (8.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 35 participants 36 participants 111 participants
Female
25
  62.5%
15
  42.9%
18
  50.0%
58
  52.3%
Male
15
  37.5%
20
  57.1%
18
  50.0%
53
  47.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 35 participants 36 participants 111 participants
Hispanic or Latino
20
  50.0%
16
  45.7%
17
  47.2%
53
  47.7%
Not Hispanic or Latino
17
  42.5%
15
  42.9%
18
  50.0%
50
  45.0%
Unknown or Not Reported
3
   7.5%
4
  11.4%
1
   2.8%
8
   7.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 35 participants 36 participants 111 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
2
   5.6%
2
   1.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.5%
0
   0.0%
0
   0.0%
1
   0.9%
White
36
  90.0%
31
  88.6%
32
  88.9%
99
  89.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   7.5%
4
  11.4%
2
   5.6%
9
   8.1%
1.Primary Outcome
Title Cohen-Mansfield Agitation Inventory (CMAI)
Hide Description The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale to assess agitation. Each item is rated on a 7-point scale of frequency, from least (1) to most frequent (7). Items are summed to calculate the CMAI total score. The CMAI total score has a range of 29-203 points; higher scores indicate more severe agitation
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set, i.e. patients who had been randomized and treated and had both a baseline value and at least 1 post-baseline value for the CMAI total score.
Arm/Group Title Placebo Pimavanserin 20 mg Pimavanserin 34 mg
Hide Arm/Group Description:

Placebo, taken as two tablets, once daily by mouth

Placebo: Placebo, taken as two tablets, once daily by mouth

Drug- pimavanserin tartrate, 20 mg, taken as two 10 mg tablets, once daily by mouth

Pimavanserin 20 mg: Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth

Drug- pimavanserin tartrate, 34 mg, taken as two 17 mg tablets, once daily by mouth

Pimavanserin 34 mg: Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth

Overall Number of Participants Analyzed 37 34 35
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 37 participants 34 participants 35 participants
70.3  (4.5) 56.9  (2.2) 68.0  (3.3)
Week 12 Number Analyzed 29 participants 28 participants 29 participants
54.3  (4.3) 52.5  (4.3) 53.7  (3.0)
Week 12 change from baseline Number Analyzed 29 participants 28 participants 29 participants
-16.8  (5.0) -3.7  (3.7) -12.3  (2.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pimavanserin 20 mg
Comments Mixed-effect model repeated measures (MMRM), with the dependent variable being the change from Baseline in CMAI total score.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 5.1
Confidence Interval (2-Sided) 95%
-4.8 to 15.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Pimavanserin 34 mg
Comments Mixed-effect model repeated measures (MMRM), with the dependent variable being the change from Baseline in CMAI total score.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-8.5 to 10.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.8
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Zarit Burden Interview
Hide Description The Zarit Burden Interview (ZBI) assess the stresses experienced by caregivers of patients with dementia. It assesses 22 questions about the impact of the patient's disabilities on the caregiver's life, each rated from least (0) to most (4) frequent. Items are summed to calculate the ZBI total score. The ZBI total score ranges from 0 to 88; higher scores denoting more stresses experienced by caregivers.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set, i.e. patients who had been randomized and treated and had both a baseline value and at least 1 post-baseline value for the CMAI total score.
Arm/Group Title Placebo Pimavanserin 20 mg Pimavanserin 34 mg
Hide Arm/Group Description:

Placebo, taken as two tablets, once daily by mouth

Placebo: Placebo, taken as two tablets, once daily by mouth

Drug- pimavanserin tartrate, 20 mg, taken as two 10 mg tablets, once daily by mouth

Pimavanserin 20 mg: Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth

Drug- pimavanserin tartrate, 34 mg, taken as two 17 mg tablets, once daily by mouth

Pimavanserin 34 mg: Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth

Overall Number of Participants Analyzed 34 33 32
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 34 participants 33 participants 32 participants
41.5  (2.6) 40.8  (2.4) 41.7  (2.5)
Week 12 Number Analyzed 28 participants 27 participants 27 participants
37.0  (3.2) 36.8  (3.7) 35.7  (3.5)
Week 12 change from baseline Number Analyzed 28 participants 27 participants 27 participants
-6.5  (2.3) -4.9  (2.3) -5.5  (2.5)
Time Frame From the time of informed consent through the completion of procedures at the Week 12 visit (for subjects continuing into an Open-Label Extension study) or through to 30 days after the last dose of study drug (for all other subjects)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Pimavanserin 20 mg Pimavanserin 34 mg
Hide Arm/Group Description

Placebo, taken as two tablets, once daily by mouth

Placebo: Placebo, taken as two tablets, once daily by mouth

Drug- pimavanserin tartrate, 20 mg, taken as two 10 mg tablets, once daily by mouth

Pimavanserin 20 mg: Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth

Drug- pimavanserin tartrate, 34 mg, taken as two 17 mg tablets, once daily by mouth

Pimavanserin 34 mg: Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth

All-Cause Mortality
Placebo Pimavanserin 20 mg Pimavanserin 34 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/40 (0.00%)      0/35 (0.00%)      0/36 (0.00%)    
Hide Serious Adverse Events
Placebo Pimavanserin 20 mg Pimavanserin 34 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/40 (7.50%)      4/35 (11.43%)      3/36 (8.33%)    
Gastrointestinal disorders       
Diverticulum * 1  0/40 (0.00%)  0 1/35 (2.86%)  1 0/36 (0.00%)  0
Lower gastrointestinal haemorrhage * 1  0/40 (0.00%)  0 1/35 (2.86%)  1 0/36 (0.00%)  0
Upper gastrointestinal haemorrhage * 1  1/40 (2.50%)  1 0/35 (0.00%)  0 0/36 (0.00%)  0
Infections and infestations       
Sepsis * 1  0/40 (0.00%)  0 1/35 (2.86%)  1 0/36 (0.00%)  0
Injury, poisoning and procedural complications       
Femoral neck fracture * 1  0/40 (0.00%)  0 1/35 (2.86%)  1 0/36 (0.00%)  0
Pelvic fracture * 1  0/40 (0.00%)  0 0/35 (0.00%)  0 1/36 (2.78%)  1
Investigations       
Weight decreased * 1  1/40 (2.50%)  1 0/35 (0.00%)  0 0/36 (0.00%)  0
Metabolism and nutrition disorders       
Hyponatraemia * 1  0/40 (0.00%)  0 1/35 (2.86%)  1 0/36 (0.00%)  0
Nervous system disorders       
Encephalopathy * 1  0/40 (0.00%)  0 1/35 (2.86%)  1 0/36 (0.00%)  0
Psychiatric disorders       
Agitation * 1  0/40 (0.00%)  0 1/35 (2.86%)  1 2/36 (5.56%)  2
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism * 1  1/40 (2.50%)  1 0/35 (0.00%)  0 0/36 (0.00%)  0
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Pimavanserin 20 mg Pimavanserin 34 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/40 (27.50%)      15/35 (42.86%)      15/36 (41.67%)    
Blood and lymphatic system disorders       
Anaemia * 1  1/40 (2.50%)  1 2/35 (5.71%)  2 0/36 (0.00%)  0
Gastrointestinal disorders       
Diarrhoea * 1  3/40 (7.50%)  3 2/35 (5.71%)  2 2/36 (5.56%)  2
Constipation * 1  1/40 (2.50%)  1 2/35 (5.71%)  2 2/36 (5.56%)  2
Gastrointestinal haemorrhage * 1  0/40 (0.00%)  0 2/35 (5.71%)  2 0/36 (0.00%)  0
Infections and infestations       
Nasopharyngitis * 1  1/40 (2.50%)  1 0/35 (0.00%)  0 2/36 (5.56%)  2
Urinary tract infection * 1  0/40 (0.00%)  0 2/35 (5.71%)  2 1/36 (2.78%)  1
Injury, poisoning and procedural complications       
Fall * 1  1/40 (2.50%)  1 3/35 (8.57%)  3 3/36 (8.33%)  3
Contusion * 1  1/40 (2.50%)  1 1/35 (2.86%)  2 2/36 (5.56%)  2
Metabolism and nutrition disorders       
Decreased appetite * 1  0/40 (0.00%)  0 2/35 (5.71%)  2 2/36 (5.56%)  2
Psychiatric disorders       
Agitation * 1  5/40 (12.50%)  5 5/35 (14.29%)  5 1/36 (2.78%)  1
Insomnia * 1  0/40 (0.00%)  0 4/35 (11.43%)  5 3/36 (8.33%)  3
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
The original study (n=432) was powered to detect a treatment effect on CMAI, however recruitment was discontinued early for business reasons and amended accordingly The final study (n=111) was no longer adequately powered to detect a treatment effect
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Investigator may publish the study results, relative to his/her own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the sponsor for review and comment. The sponsor has 60 days to review and comment.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sr. Dir. Medical Information and Medical Communications
Organization: ACADIA Pharmaceuticals Inc.
Phone: 858-261-2897
EMail: medicalinformation@acadia-pharm.com
Layout table for additonal information
Responsible Party: ACADIA Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02992132    
Other Study ID Numbers: ACP-103-032
2016-001127-32 ( EudraCT Number )
First Submitted: December 12, 2016
First Posted: December 14, 2016
Results First Submitted: January 25, 2019
Results First Posted: March 28, 2019
Last Update Posted: March 28, 2019