Trial Outcomes & Findings for A Study of the Safety and Efficacy of Pimavanserin in Patients With Alzheimer's Disease Psychosis (NCT NCT02035553)

NCT ID: NCT02035553

Last Updated: 2017-10-25

Results Overview

Change from Baseline to Day 43 in the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) psychosis score (Delusions \[Domain A\]+Hallucinations \[Domain B\]) in the Full Analysis Set (FAS). The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains. For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), The NPI-NH Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual domain scores, to yield a possible total score of 0 to 24. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

181 participants

Primary outcome timeframe

Day 43

Results posted on

2017-10-25

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo, two tablets, once daily by mouth	Pimavanserin 40 mg Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
Overall Study STARTED	91	90
Overall Study COMPLETED	73	67
Overall Study NOT COMPLETED	18	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo, two tablets, once daily by mouth	Pimavanserin 40 mg Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
Overall Study Death (See All-Cause Mortality Table)	0	1
Overall Study Adverse Event	10	6
Overall Study Physician Decision	3	2
Overall Study Lack of Efficacy	1	1
Overall Study Withdrawal by Subject	4	7
Overall Study Non-compliance with Study Drug	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Other Reason	0	4

Baseline Characteristics

A Study of the Safety and Efficacy of Pimavanserin in Patients With Alzheimer's Disease Psychosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=91 Participants Placebo, two tablets, once daily by mouth	Pimavanserin 40 mg n=90 Participants Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)	Total n=181 Participants Total of all reporting groups
Age, Continuous	86.1 years STANDARD_DEVIATION 5.96 • n=5 Participants	85.7 years STANDARD_DEVIATION 7.05 • n=7 Participants	85.9 years STANDARD_DEVIATION 6.51 • n=5 Participants
Age, Customized Age · <=85	41 Participants n=5 Participants	41 Participants n=7 Participants	82 Participants n=5 Participants
Age, Customized Age · >85	50 Participants n=5 Participants	49 Participants n=7 Participants	99 Participants n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	73 Participants n=7 Participants	146 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	91 Participants n=5 Participants	90 Participants n=7 Participants	181 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	89 Participants n=5 Participants	84 Participants n=7 Participants	173 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United Kingdom	91 participants n=5 Participants	90 participants n=7 Participants	181 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 43

Population: All randomized subjects who received at least one dose of study treatment and have both a Baseline and at least one post-Baseline NPI-NH psychosis score evaluation.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Placebo, two tablets, once daily by mouth	Pimavanserin 40 mg n=87 Participants Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
Antipsychotic Efficacy	-1.93 Score on the NPI-NH scale Interval -3.18 to -0.67	-3.76 Score on the NPI-NH scale Interval -5.05 to -2.47

Adverse Events

Placebo

Serious events: 10 serious events

Other events: 70 other events

Deaths: 4 deaths

Pimavanserin 40 mg

Serious events: 15 serious events

Other events: 67 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

James Youakim, Vice President, Clinical Development

ACADIA Pharmaceuticals Inc.

Phone: 609-250-6900

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=91 participants at risk Placebo, two tablets, once daily by mouth	Pimavanserin 40 mg n=90 participants at risk Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
Cardiac disorders Cardiopulmonary failure	1.1% 1/91 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	0.00% 0/90 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Cardiac disorders Myocardial infarction	2.2% 2/91 • Number of events 2 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	0.00% 0/90 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
General disorders General physical health deterioration	1.1% 1/91 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	0.00% 0/90 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Infections and infestations Pneumonia	2.2% 2/91 • Number of events 2 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	2.2% 2/90 • Number of events 3 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Infections and infestations Urinary tract infection	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	2.2% 2/90 • Number of events 2 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Infections and infestations Bronchopneumonia	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Infections and infestations Lower respiratory tract infection	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Fall	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Laceration	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Spinal fracture	1.1% 1/91 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	0.00% 0/90 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Upper limb fracture	1.1% 1/91 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	0.00% 0/90 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Wrist fracture	1.1% 1/91 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	0.00% 0/90 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of thorax	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Nervous system disorders Dementia	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Nervous system disorders Depressed level of consciousness	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Nervous system disorders Loss of consciousness	1.1% 1/91 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Nervous system disorders Transient ischaemic attack	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Psychiatric disorders Aggression	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Renal and urinary disorders Renal failure acute	0.00% 0/91 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	1.1% 1/90 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Vascular disorders Hypotension	1.1% 1/91 • Number of events 1 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	0.00% 0/90 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.

Measure	Placebo n=91 participants at risk Placebo, two tablets, once daily by mouth	Pimavanserin 40 mg n=90 participants at risk Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
Blood and lymphatic system disorders Anaemia	8.8% 8/91 • Number of events 8 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	10.0% 9/90 • Number of events 9 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
General disorders Oedema peripheral	2.2% 2/91 • Number of events 2 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	7.8% 7/90 • Number of events 7 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Infections and infestations Urinary tract infection	27.5% 25/91 • Number of events 36 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	20.0% 18/90 • Number of events 27 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Infections and infestations Lower respiratory tract infection	13.2% 12/91 • Number of events 13 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	14.4% 13/90 • Number of events 15 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Infections and infestations Cellulitis	3.3% 3/91 • Number of events 3 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	6.7% 6/90 • Number of events 7 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Fall	23.1% 21/91 • Number of events 35 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	22.2% 20/90 • Number of events 39 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Contusion	15.4% 14/91 • Number of events 17 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	12.2% 11/90 • Number of events 16 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Injury, poisoning and procedural complications Laceration	5.5% 5/91 • Number of events 6 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	3.3% 3/90 • Number of events 3 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Investigations Blood urea increased	8.8% 8/91 • Number of events 8 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	7.8% 7/90 • Number of events 7 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Investigations Blood potassium increased	3.3% 3/91 • Number of events 3 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	5.6% 5/90 • Number of events 5 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Investigations Blood lactate dehydrogenase increase	11.0% 10/91 • Number of events 10 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	4.4% 4/90 • Number of events 4 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Investigations Blood alkaline phosphatase increased	8.8% 8/91 • Number of events 8 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	3.3% 3/90 • Number of events 3 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Metabolism and nutrition disorders Hyperglycaemia	12.1% 11/91 • Number of events 11 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	4.4% 4/90 • Number of events 4 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Nervous system disorders Somnolence	7.7% 7/91 • Number of events 7 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	3.3% 3/90 • Number of events 3 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Psychiatric disorders Agitation	14.3% 13/91 • Number of events 13 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	21.1% 19/90 • Number of events 19 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Psychiatric disorders Aggression	4.4% 4/91 • Number of events 4 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	10.0% 9/90 • Number of events 10 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Psychiatric disorders Anxiety	2.2% 2/91 • Number of events 2 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	5.6% 5/90 • Number of events 5 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Psychiatric disorders Behavioural and psychiatric symptoms of dementia	2.2% 2/91 • Number of events 2 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	5.6% 5/90 • Number of events 6 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.
Skin and subcutaneous tissue disorders Rash	7.7% 7/91 • Number of events 7 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.	4.4% 4/90 • Number of events 4 • 12 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.