A Multi-Center, Open-Label Extension Study to Examine the Safety and Tolerability of ACP-103 in the Treatment of Psychosis in Parkinson's Disease
Phase: PHASE3
Conditions: Parkinson's Disease Psychosis
Sponsor: ACADIA Pharmaceuticals Inc.

Official Title: A multi-center, open-label extension study to examine the safety and 
tolerability of ACP-103 in the treatment of psychosis in Parkinson’s Disease 
NCT Number: NCT00550238 
Date of IRB Approval: 16 Jul 2010 

 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 
 
ACADIA Pharmaceuticals Inc. 
 
 
CLINICAL STUDY PROTOCOL 
 
A Multi-Center, Open-Label Extension Study to 
Examine the Safety and Tolerability of ACP-103 in the 
Treatment of Psychosis in  
Parkinson’s Disease 
 
 
 
 
 
 
Protocol Number: ACP-103-015 
 
EUDRACT Number: 2007-003035-22 
 
 
Protocol Amendment No. 6 Date:  June 30, 2010 
Protocol Amendment No. 5 Date: August 4, 2008 
Protocol Amendment No. 4 Date: April 14, 2008 
Protocol Amendment No. 3 Date: November 14, 2007 
Protocol Amendment No. 2 Date: August 30, 2007 
Protocol Amendment No. 1 Date: June 14, 2007 
Final Protocol Date: April 12, 2007 
 
   
Confidentiality Statement 
This protocol is the confidential information of ACADIA Pharmaceuticals Inc. and is intended solely for the 
guidance of the clinical investigation.  This protocol may not be disclosed to parties not associated with the clinical 
investigation or used for any purpose without the prior written consent of ACADIA Pharmaceuticals Inc. 

A CADI A Pharmaceuticals 
Protocol Amendment #6 ACP-103-015 
Sponsor Signatory: 
Sponsor Team Lead: 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
Page 2 
June 30, 2010 

ACADIA Pharmaceuticals  
 
Page 3 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
PROTOCOL SYNOPSIS 
Title 
A Multi-Center, Open-Label Extension Study to Examine the Safety 
and Tolerability of Pimavanserin in the Treatment of Psychosis in 
Parkinson’s Disease 
Protocol Number 
ACP-103-015 
Methodology 
This study will be conducted as a multi-center, open-label extension 
study.  Subjects who have completed blinded treatment in a previous 
study of pimavanserin in Parkinson’s disease psychosis, and who may, 
in the opinion of the Investigator, benefit from treatment with 
pimavanserin, will be enrolled in this extension study for safety 
evaluation.  Subjects may be enrolled in ACP-103-015 as early as the 
last visit of the treatment phase of the prior blinded study OR up to 28 
days following completion of this blinded treatment period.  
Subjects who enroll in ACP-103-015 within one week of completion 
of the treatment phase of the prior blinded study will NOT be required 
to complete a full Baseline visit (Day 1).   
Subjects who are enrolled greater than one week following completion 
of the prior blinded study will be required to complete a full baseline 
evaluation for ACP-103-015. 
Once per day, subjects will be administered 40 mg of pimavanserin, 
orally, preferably in the morning.  Dose escalation and reduction will 
NOT be allowed.     
All subjects will be required to visit the study site at Week 2, Month 1, 
Month 3, Month 6, Month 9, Month 12 and every six months 
thereafter to complete safety and clinical evaluations. Unscheduled 
clinical evaluations may occur at anytime if deemed appropriate by the 
Investigator. 
Study Duration  
The duration of this extension study will be determined based on 
clinical grounds, but may continue for as long as pimavanserin is 
considered to be tolerated and beneficial to subjects and until such 
time as pimavanserin is approved and commercially available.  
Study Centers 
This is a multi-center study with approximately 150 sites  
Objectives 
Primary Objective: 
• To assess long-term safety and tolerability of pimavanserin in 
subjects with Parkinson’s Disease Psychosis (PDP)  
Number of 
Subjects 
All subjects that complete the blinded treatment period of a previous 
study of pimavanserin in PDP and meet eligibility criteria may enroll 
in this study.   

ACADIA Pharmaceuticals  
Page 4 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
Inclusion/Exclusion 
Criteria 
The study population is defined as subjects who meet the following 
criteria: 
Inclusion Criteria: 
1. Subject has completed the blinded treatment period of a previous
study of pimavanserin in PDP within the last 28 days and, who
may, in the opinion of the Investigator, benefit from therapy with
pimavanserin
2. Subject must have clear sensorium at study entry (i.e., oriented to
time, person, and place) and thus not be delirious
3. Female subjects must be of non-childbearing potential (defined as
either surgically sterilized or at least 1 year post-menopausal) or
must agree to use a clinically acceptable method of contraception
(such as intrauterine device [IUD], diaphragm, or oral, injectable
[e.g. Depo-Provera] or implantable contraception [e.g. Norplant
System]) during the study and one month following completion of
the study
4. The subject is willing and able to provide consent
5. Caregiver is willing and able to provide consent and agrees to
accompany the subject to all visits
Exclusion Criteria: 
1. Subject has current evidence of a clinically significant concurrent
medical illness including: severe cardiac disease (recent
myocardial infarction, congestive heart failure or cardiac syncope),
severe pulmonary disease (chronic obstructive pulmonary disease
or emphysema), renal insufficiency or failure, hepatitis, a recent
diagnosis of malignancy (excluding basal or squamous cell
carcinoma), a serious and or unstable gastrointestinal, hematologic
or other medical disorder
2. Subject is using any of the medications prohibited or restricted as
described in Appendix 1 (Prohibited and Restricted Concomitant
Medications
3. Subject is on medications known to prolong the QT interval (as 
described in Appendix 1)
4. Subject has a baseline electrocardiogram (ECG) with Bazett’s
corrected QT  (QTcB) of greater than 460 msec if male or 470
msec if female
5. Subject had an allergy or sensitivity to pimavanserin based on
known allergies to drugs of the same class
6. Subject is judged by the Investigator to be inappropriate for the
study

ACADIA Pharmaceuticals  
 
Page 5 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
Study Product, 
Dose, Route, 
Regimen 
Pimavanserin will be administered orally, once a day.  Two 20 mg 
tablets will be used to administer a 40 mg dose.  Dose escalation and 
reduction will not be allowed.  
Criteria for 
Evaluation  
Safety: 
• The safety of subjects will be assessed by monitoring adverse 
events, physical examinations, vital signs, clinical laboratory tests 
(hematology, clinical chemistry, and urinalysis), ECGs, and pre-
dose plasma pimavanserin concentrations 
 
Six clinical rating scales will be administered and data will be 
recorded for the following: 
 
• The combined score for the Hallucinations and Delusions domains 
of the Scale for the Assessment of Positive Symptoms (SAPS). 
• Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III 
• Clinical Global Impression Scale (CGI) with emphasis on severity 
(CGI-S) and improvement (CGI-I) of psychosis 
• The Caregiver Burden Scale 
• Resource Utilization in Dementia Scale (RUD Lite) 
Statistical Analyses  Safety analyses will be conducted on adverse events, clinical 
laboratory tests, ECGs, physical exams and vital signs. No formal 
analyses will be conducted on the clinical efficacy data. 

ACADIA Pharmaceuticals  
Page 6 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
TABLE OF CONTENTS 
SIGNATURES ....................................................................................................................... 2 
PROTOCOL SYNOPSIS ...................................................................................................... 3 
TABLE OF CONTENTS ...................................................................................................... 6 
LIST OF ABBREVIATIONS ............................................................................................... 9 
1.
BACKGROUND INFORMATION .......................................................................... 11
1.1 
INVESTIGATIONAL DRUG .................................................................................... 12 
1.2 
PREVIOUS CLINICAL EXPERIENCE ...................................................................................... 12 
1.3 
RATIONALE FOR THE STUDY ................................................................................................ 13 
2. OBJECTIVES ................................................................................................................. 14
3. STUDY DESIGN ............................................................................................................. 14
3.1 
OVERALL STUDY DESIGN ................................................................................... 14 
3.2 
DOSE RATIONALE ............................................................................................... 14 
3.3 
STUDY DURATION ............................................................................................... 14 
3.4 
NUMBER OF SUBJECTS ........................................................................................ 15 
3.5 
ADMINISTRATION OF PIMAVANSERIN ................................................................. 15 
3.6 
STUDY PROCEDURES ........................................................................................... 15 
3.6.1.Schedule of Events and Assessments .................................................................... 15 
3.6.2.Evaluations by Visit ................................................................................................... 19 
4. SELECTION OF SUBJECTS AND CRITERIA FOR WITHDRAWAL ...................... 21
4.1 
SELECTION OF SUBJECTS ..................................................................................... 21 
4.2 
CRITERIA FOR SUBJECT WITHDRAWAL ............................................................... 22 
5. TREATMENTS ADMINISTERED ............................................................................................... 23
5.1 
IDENTITY OF INVESTIGATIONAL PRODUCTS ........................................................ 23 
5.2 
DOSING ............................................................................................................... 23 
5.3 
CONCOMITANT THERAPY .................................................................................... 23 
5.3.1.Prohibited and Restricted Medications ................................................................. 24 
5.4 
INVESTIGATIONAL DRUG HANDLING .................................................................. 24 
5.4.1.Test Article ................................................................................................ 24 
5.4.2.Drug Packaging ......................................................................................... 24 
5.4.3.Dosage and Administrations ..................................................................... 24 
5.4.4.Receipt of Supplies ................................................................................... 24 
5.4.5.Storage of Investigational Drug ................................................................ 24 
5.4.6.Record of Dispensing ................................................................................ 25 

ACADIA Pharmaceuticals  
 
Page 7 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
5.4.7.Accountability ........................................................................................... 25 
6. ASSESSMENT OF SAFETY ........................................................................................................... 25 
6.1 
PRIMARY OBJECTIVE .......................................................................................... 25 
6.2 
DESCRIPTION OF SAFETY ASSESSMENTS ............................................................. 25 
6.2.1. Updated Medical History ......................................................................... 25 
6.2.2. Physical Examinations and Updated Physical Examinations .................. 26 
6.2.3. Weight .................................................................................................... 26 
6.2.4. Electrocardiogram (ECG) ........................................................................ 26 
6.2.5. Vital Signs ................................................................................................ 27 
6.2.6. Clinical Laboratory Tests ......................................................................... 27 
6.2.7. Adverse Events ........................................................................................ 29 
6.2.8. Overdose of Investigational Medicinal Product....................................... 34 
6.2.9. Pregnancy ................................................................................................. 34 
6.2.10. Emergency Treatment ............................................................................ 34 
7. CLINICAL EVALUATIONS ........................................................................................................... 34 
7.1 
SCALE FOR ASSESSMENT OF POSITIVE SYMPTOMS (SAPS) ................................. 34 
7.2 
UNIFIED PARKINSON’S DISEASE RATING SCALE (UPDRS) ................................ 35 
7.3 
CLINICAL GLOBAL IMPRESSION SCALE (CGI) .................................................... 36 
7.4 
CAREGIVER BURDEN SCALE ............................................................................... 36 
7.5 
RUD LITE ........................................................................................................... 36 
8. ASSESSMENT OF PHARMACOKINETICS .......................................................................... 37 
9. DATA RECORDING, RETENTION, AND MONITORING ............................................. 37 
9.1 
CASE REPORT FORMS ......................................................................................... 37 
9.2 
AVAILABILITY AND RETENTION OF RECORDS ..................................................... 37 
9.3 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................. 38 
9.4 
SUBJECT CONFIDENTIALITY ................................................................................ 38 
10. STATISTICAL PLAN ....................................................................................................................... 39 
10.1 GENERAL STATISTICAL METHODS ...................................................................... 39 
10.2 STUDY SUBJECTS ................................................................................................ 39 
10.2.1. Analysis Population(s) ........................................................................... 39 
10.2.2. Subject Accountability and Subject Disposition .................................... 39 
11. DEMOGRAPHIC AND BASELINE CHARACTERISTICS ........................................... 39 
12. SAFETY ANALYSIS ......................................................................................................................... 39 
12.1 ADVERSE EVENTS ............................................................................................... 39 
12.1.1. Clinical Laboratory Values ............................................................................. 39 

ACADIA Pharmaceuticals  
 
Page 8 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
12.1.2. Vital Signs ............................................................................................................ 39 
12.1.3. Electrocardiogram .............................................................................................. 40 
12.1.4. Physical Examinations ...................................................................................... 40 
12.1.5. Pharmacokinetic Analysis ............................................................................... 40 
12.2 EFFICACY ANALYSIS ........................................................................................... 40 
13. REGULATORY COMPLIANCE ................................................................................................ 40 
13.1 ETHICAL CONDUCT OF THE STUDY ..................................................................... 40 
13.2 REGULATORY APPROVAL ................................................................................... 40 
13.3 SUBJECT INFORMED CONSENT ............................................................................ 41 
13.4 SUBJECT COMPENSATION FOR ADVERSE EFFECTS ON HEALTH ........................... 41 
13.5 PROTOCOL AMENDMENTS AND STUDY TERMINATION ........................................ 42 
13.6 FINANCE, INSURANCE AND INDEMNITY .............................................................. 42 
13.7 PUBLICATION ...................................................................................................... 42 
14. DECLARATION OF INVESTIGATOR ................................................................................... 43 
15. REFERENCES ..................................................................................................................................... 44 
16. APPENDICES ................................................................................................................ 46 
APPENDIX 1:  PROHIBITED AND RESTRICTED CONCOMITANT MEDICATIONS ................ 47 
APPENDIX 2: CAREGIVER BURDEN SCALE ..................................................................... 48 
APPENDIX 3: SCALE FOR THE ASSESSMENT OF POSITIVE SYMPTOMS (SAPS) ............... 49 
APPENDIX 4: UNIFIED PARKINSON’S DISEASE RATING SCALE (UPDRS) ...................... 62 
APPENDIX 5: CLINICAL GLOBAL IMPRESSION (CGI) SCALES ........................................ 72 
APPENDIX 6: RESOURCE UTILIZATION IN DEMENTIA (RUD LITE) ................................ 73 
 
LIST OF TABLES 
 
TABLE 1: 
SCHEDULE OF EVENTS AND ASSESSMENTS ............................................................................. 17 
TABLE 2: 
INVESTIGATIONAL PRODUCTS .................................................................................................... 23 

ACADIA Pharmaceuticals Inc. 
 
Page 9 
Protocol Amendment #5 ACP-103-015 
 
June 30, 2010 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
LIST OF ABBREVIATIONS  
Abbreviation/Acronym Definition 
5HT2A 
serotonin 2A receptor 
5HT2C 
serotonin 2C receptor 
ACADIA 
ACADIA Pharmaceuticals Incorporated, Study Sponsor 
AE(s) 
adverse event(s) 
BP 
blood pressure 
bpm 
beats per minute 
CGI-I 
Clinical Global Impression scale - Improvement 
CGI-S 
Clinical Global Impression scale - Severity 
CRF 
case report form 
D2 
dopamine D2 receptor subtype 
DBP 
diastolic blood pressure 
DO 
Doctor of Osteopathy 
EC 
Ethics Committee 
ECG 
electrocardiogram (or electrocardiograph) 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
MD 
Doctor of Medicine (Latin: Medicinae Doctor) 
mmHg 
millimeters of mercury 
PA 
physician assistant 
PD 
Parkinson’s Disease 
PDP 
Parkinson’s Disease Psychosis 
PK 
Pharmacokinetic 
po 
by mouth (Latin: per os) 
PR 
PR interval on an electrocardiogram tracing 
QRS 
QRS interval of electrocardiogram 
QT 
QT interval of electrocardiogram 
QTcB 
QT interval of electrocardiogram; Bazett’s corrected for heart rate  
ROS 
review of symptoms 

ACADIA Pharmaceuticals  
 
Page 10 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
RR 
respiration rate 
RUD Lite 
Resource Utilization in Dementia Lite 
SAE(s) 
serious adverse event(s) 
SAPS 
Scale for the Assessment of Positive Symptoms 
SBP 
systolic blood pressure 
SOP(s) 
standard operating procedure(s) 
UPDRS 
Unified Parkinson’s Disease Rating Scale 
U.S. 
United States 
 

ACADIA Pharmaceuticals  
 
Page 11 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
1. 
BACKGROUND INFORMATION 
Parkinson’s disease (PD) is a common progressive neurodegenerative disorder; its clinical 
diagnosis is based on the presence of a core set of neurological symptoms including rest tremor, 
bradykinesia, rigidity, and disturbances of balance and posture. Patients also experience a 
number of nonmotor symptoms that are equally important to address. These include psychosis 
and behavioral disturbances, pain, sensory complaints, depression, and dementia (Weintraub and 
Stern, 2005; Aarsland et al., 1999). Among these, perhaps the most significant with respect to 
morbidity and quality of life, and the most difficult to treat, is psychosis. Psychotic symptoms 
occur in 20% to 40% of patients with PD in advanced stages of the disease (Marsh, 2005; 
Fenelon, 2000). Parkinson’s disease psychosis (PDP) manifests primarily as hallucinations and 
delusions; initial symptoms are frequently a sense of presence or passage. 
 
Development of psychosis in a patient with PD is progressive and often devastating as it is 
prognostic of nursing home placement, poses enormous stress on caregivers, and markedly 
increases the risk of mortality in the patient population (Chou and Fernandez, 2006; Factor et al., 
2003). There is no proven safe and effective course of treatment for PDP. Dose reduction of 
dopaminergic treatment is frequently standard practice when psychotic symptoms first present, 
but this practice does not always diminish psychosis and provides only short-term antipsychotic 
benefit. In addition, it usually results in increased motor function deficits.  
 
There are six atypical antipsychotics on the market in the United States (U.S.): aripiprazole, 
clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.  None of these agents are 
approved for the treatment of PDP.  Nevertheless, off-label use of these agents is sometimes 
employed.  The most commonly used for PDP are clozapine and quetiapine. Clozapine is 
effective in PDP and does not cause deterioration of motor function. However, the prescribing 
community is often reluctant to employ clozapine as a first line therapy in the PDP population 
because of (1) the risk of agranulocytosis, (2) the stringent, associated monitoring requirements, 
and (3) other potential idiosyncratic reactions such as myocarditis and cardiomyopathy. 
Quetiapine appears to be the next best option because it minimally affects motor function. In two 
blinded and placebo-controlled trials, quetiapine had no effect on motor function but failed to 
show improvement in psychotic symptoms (Ondo et al., 2005, and Rabey et al., 2006). 
Risperidone and olanzapine have been shown to worsen motoric symptoms in PDP patients and 
are therefore considered inappropriate therapy in this population. More recently, two case studies 
suggest that ziprasidone may be useful in treating PDP, however, the cardiovascular safety 
profile and potential effects on motor function may limit its use. The available data on 
aripiprazole suggest that this agent has variable effects on psychotic symptoms and based on its 
safety profile it should be used with caution in this fragile patient population, because it may 
cause motor worsening. 
 
In addition to the risk of motor effects associated with the other atypical antipsychotics, sedation 
is a serious side effect in this population, which increases risks of falls and fractures. This patient 
population is already at risk given the tendency for frequent somnolence and sleep attacks to 
occur during the day. In addition, a black box warning was recently applied to the label of 
atypical antipsychotics regarding their use in elderly patients with dementia. The Food and Drug 

ACADIA Pharmaceuticals  
 
Page 12 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
Administration (FDA) determined in 2005 that the treatment of behavioral disorders in elderly 
patients with dementia with atypical antipsychotic medications is associated with increased 
mortality. Of a total of 17 placebo-controlled trials performed with olanzapine, aripiprazole, 
risperidone, or quetiapine in elderly demented patients with behavioral disorders, 15 showed 
higher mortality in the drug-treated arm compared with the placebo-treated arm (FDA Public 
Health Advisory issued 11 April 2005). Moreover, a retrospective cohort study, reported that 
typical antipsychotics are as likely as atypical antipsychotics to increase the risk of death in 
elderly patients (Wang et al., 2005), suggesting the dopamine D2 receptor subtype (D2) rather 
than the serotonin 2A receptor (5HT2A) may be involved in the increased mortality. 
 
1.1 
Investigational Drug 
Pimavanserin (pimavanserin tartrate, or ACP-103) is the tartrate salt of the active moiety N-(4-
fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)- N’-(4-(2-
methylpropyloxy)phenylmethyl)carbamide (2R,3R)-dihydroxybutanedioate (2:1) and is a novel 
small molecule designed to specifically block serotoninergic neurotransmission mediated by the 
5HT2A receptor. At higher doses pimavanserin may block the serotonin 5HT2C receptors. 
 
Although the etiology of PDP is unclear, both scientific and clinical observations support the use 
of a 5HT2A receptor inverse agonist, such as pimavanserin, in this indication (Weiner et al., 
2003). Furthermore, pimavanserin does not bind to dopamine D2 receptors that have been 
implicated in a range of dose-limiting side effects of the existing antipsychotic drugs as well as 
an increased risk of mortality in elderly patients with dementia (Wang, et al., 2005). On the basis 
of its novel receptor binding profile, pimavanserin may be effective in PDP and have an 
improved safety profile relative to other antipsychotic agents. 
 
1.2 
Previous Clinical Experience 
 
ACADIA has initiated 17 clinical trials of pimavanserin.  Fifteen of these studies are completed 
and 2 studies are ongoing (Study ACP-103-010 and Study ACP-103-015).  Of the 15 completed 
studies, 14 have been analyzed; analysis is ongoing for the other study (ACP-103-014).  The 2 
ongoing studies, Study ACP-103-010 and Study ACP-103-015, are open-label safety trials.  A 
total of 882 subjects have had exposure to pimavanserin. Of these subjects, 447 were PD/PDP 
patients, 258 were healthy volunteers and 177 were schizophrenic patients.  In a long-term, open-
label safety trial in PDP patients (Study ACP-103-010), 23 subjects have received pimavanserin 
for > 12 months, including 13 subjects treated for ≥ 24 months and 2 subjects treated for > 60 
months.  As of May 1st, 2010, both those subjects remain active. 
 
In the other long-term, open-label safety trial in PDP subjects (ACP-103-015), 77 subjects have 
received pimavanserin for > 12 months and 6 subjects have received pimavanserin for > 24 
months.  As of May 1st, 2010, 160 subjects remain active. 
 
All studies have been, or are being, conducted in accordance with Good Clinical Practice, the 
ethical principles that have their origin in the Declaration of Helsinki, and applicable local 
regulatory requirements. 

ACADIA Pharmaceuticals  
 
Page 13 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
Across study populations (healthy volunteers as well as patients), pimavanserin has been shown 
to be generally safe and well tolerated at single doses up to 300 mg and multiple doses up to 160 
mg. The most common adverse events (AEs) were similar in healthy normal volunteers, PD 
patients, and schizophrenia patients and occurred at a similar frequency between pimavanserin- 
and placebo-treated subjects. The majority of AEs reported in studies to date were considered 
mild to moderate in nature.  
 
Central nervous system and gastrointestinal disturbances were the most common AEs. Central 
nervous system events included headache, postural dizziness, somnolence (drowsiness), and 
dizziness. Gastrointestinal disturbances included nausea, constipation, dyspepsia, and vomiting; 
severe nausea and vomiting occurred and were dose-limiting in a few cases. Other reported, but 
less common, AEs included psychiatric conditions such as confusion and hallucinations. 
Cardiac-related and cardiovascular AEs were infrequent and included ventricular tachycardia, 
bradycardia, and vasovagal and syncopal episodes. Other infrequent AEs included orthostatic 
hypotension, asthenia, fatigue, peripheral edema, and injury especially due to a fall. 
 
 
 
 
 
  Although the number of SAEs in the 
Parkinson’s disease patients who received pimavanserin may appear disproportionately high, this 
group reflects subjects who participated in the long-term open label safety extension studies 
where duration of dosing is markedly longer than in the other groups. 
 
1.3 
Rationale for the Study 
Given the persistent and progressive nature of PDP, an active therapeutic intervention is needed 
that could effectively manage psychotic symptoms without reducing control of motor function or 
increasing the risk for sedation, hematologic disorders, significant cardiovascular events, or 
mortality in this older and fragile patient population.  
 
Like all of the atypical antipsychotics, pimavanserin shows high potency and efficacy as a 
competitive antagonist and inverse agonist at the 5-HT2A receptor. Importantly for its potential 
use in PD subjects, pimavanserin has no affinity or functional activity at D2 receptors. Thus, 
pimavanserin may offer antipsychotic benefit in this subject population with an acceptable risk 
profile. Results of previously completed trials of pimavanserin in PDP indicate that pimavanserin 
reduced psychosis without worsening motor function.  These data support the continued 
development of pimavanserin for the treatment of PDP. 
 
ACADIA Pharmaceuticals Inc. (ACADIA) is currently planning to conduct additional double-
blind, placebo-controlled studies to assess the efficacy and safety of pimavanserin in the 
treatment of PDP.   
 

ACADIA Pharmaceuticals  
 
Page 14 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
2. 
OBJECTIVES 
 
Primary Objective:  
• To assess long-term safety and tolerability of pimavanserin for the treatment of PDP  
 
3. 
STUDY DESIGN 
3.1 
Overall Study Design 
Pimavanserin will be administered once daily at a fixed dose level of 40 mg.  The study will be 
conducted on an outpatient basis.   
 
Subjects who have completed the treatment period of a previous blinded study of pimavanserin 
in PDP subjects and who may, in the opinion of the Investigator, benefit from continued 
treatment with pimavanserin will be enrolled in this study for safety evaluation.  Subjects may be 
enrolled in this study as early as the last visit of the treatment phase of the previous study OR up 
to 28 days following completion of the treatment period.  
 
Subjects will be required to visit the clinic on Week 2 (Day 14 ± 3 days), Month 1 (Day 28 ± 3 
days), Month 3 (Day 84 ± 7 days), Month 6 (168 days + 7 days), Month 9 (252 days + 7 days), 
Month 12 (336 days + 7 days) and every six months thereafter (every 168 days ± 7 days).  
Unscheduled clinical evaluations may occur at anytime if deemed appropriate by the 
Investigator.  If the subject terminates the study at any time other than a planned visit the subject 
will be required to visit the clinic for an end-of-study evaluation.   
 
3.2 
Dose Rationale  
 
In previous studies of pimavanserin in the PDP population, doses of 20 mg and 40 mg of 
pimavanserin have demonstrated a consistent signal of efficacy across a number of measures, 
including the SAPS, CGI-I, SCOPA nighttime sleep measure and caregiver burden scale. 
Additionally, current long-term open-label studies of pimavanserin in PDP have demonstrated 
that pimavanserin is safe and tolerable at doses of 40 mg and 60 mg.  Thus, 40 mg pimavanserin 
was chosen for this study. 
 
3.3 
Study Duration 
The duration of treatment for any individual subject will be determined based on clinical 
grounds, but may continue for as long as pimavanserin is considered to be tolerated and 
beneficial, or until such time as pimavanserin is approved and commercially available. 

ACADIA Pharmaceuticals  
 
Page 15 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
3.4 
Number of Subjects 
This study may include any eligible subject (as specified in Section 4.1) that completed the 
blinded treatment period of a previous study of pimavanserin in PDP subjects.  At least 400 
subjects are anticipated to be enrolled into ACP-103-015.       
3.5 
Administration of Pimavanserin 
Pimavanserin will be supplied as 20 mg tablets.  Subjects will take a total daily dose of 40 mg 
once daily, administered orally as two 20 mg tablets.  
3.6 
Study Procedures 
Before any subjects may be enrolled in the study, ACADIA and/or designee must obtain a copy 
of essential documents including the following: 
 
• Institutional Review Board (IRB) or Ethics Committee (EC) approval of the protocol and 
Investigator’s Brochure 
• IRB- or EC-approved Informed Consent Form (ICF) 
• Health Insurance Portability and Accountability Act (HIPAA) form (where appropriate) 
• Other documents required by local regulations, as applicable 
 
Each subject and their caregiver must sign the approved ICF and, where appropriate, HIPAA 
forms during the Baseline visit.  Study eligibility will be assessed at the Baseline visit (Visit 1). 
Each subject who meets all eligibility criteria will be assigned a unique identification number. 
No subject will be enrolled twice in the study. Once the identification number has been assigned 
to a subject, no attempt should be made to use that number again. 
 
3.6.1. 
Schedule of Events and Assessments 
Table 1 displays the schedule of events and assessments. 
 
This study will be conducted on an outpatient basis.  Subjects may be enrolled in this study as 
early as the last visit of the treatment period of the previous blinded study of pimavanserin in 
PDP OR up to 28 days following completion of the treatment period of the previous study.   
Subjects who enroll in ACP-103-015 within one week from completion of their participation in 
the previous blinded study should have completed all safety and efficacy assessments for the 
final Study Day as detailed in the previous study.  In addition, subjects must be eligible for 
participation in this study and sign an informed consent form as required at the Baseline visit 
(Day 1) of this study.  These subjects will NOT be required to complete a full Baseline visit as 
detailed in the Schedule of Events and Assessments.   
 
Subjects who are enrolled greater than one week following completion of the previous blinded 
study of pimavanserin for PDP will be required to complete a baseline evaluation that will 
include subject eligibility, an updated medical history, vital signs, weight, a physical exam, 
clinical laboratory tests, pregnancy test, a 12-lead electrocardiogram (ECG), adverse event 
questionnaire, and assessment of prior and concomitant medications.  
 

ACADIA Pharmaceuticals  
 
Page 16 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
Subjects will be started on 40 mg of pimavanserin, administered orally, once per day, preferably 
in the morning during the baseline visit.  Dose escalation or reduction will NOT be allowed.     
All subjects will be required to visit the study site at Week 2, Month 1, Month 3, Month 6, 
Month 9, Month 12 and every six months thereafter to complete safety and clinical evaluations.  
Unscheduled clinical evaluations may occur at anytime if deemed appropriate by the 
Investigator. If the subject terminates the study at any time other than a planned visit the subject 
will be required to visit the clinic for an end-of-study evaluation.   

ACADIA Pharmaceuticals Inc. 
 
Page 17 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
Table 1: Schedule of Events and Assessments  
  
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
 
Baseline1 
(Day 1) 
 Week 2 
Day 14     
± 3 days 
 Month 1 
Day 28      
± 3 days 
Month 3 
Day 84 
+ 7days 
Month 6 
Day 168 
+ 7days 
Month 9 
Day 252 
+ 7days 
Month 12 
(Day 336 ± 7 days) 
AND 
every 6 months 
thereafter 
(168 days ± 7 days) 
End-of-Study 
(if subject 
withdraws or 
is terminated 
from the 
study) 
Informed Consent 
X 
 
 
 
 
 
 
 
Medical History 
X2 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam3 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Labs 
X 
X 
X 
X 
X 
X 
X 
X 
Serum Pregnancy Test 
X 
 
 
X 
X 
X 
X 
X 
Plasma PK Sample4 
 
X 
X 
X 
X 
X 
X 
X 
Caregiver Burden Scale 
 
X 
X 
X 
X 
X 
X 
X 
                                                 
1 Subjects that enroll in this study within one week of completion from a previous blinded study of pimavanserin in will only be required to sign an informed consent form, 
complete an update to the medical history that was performed during the screening and baseline visit of the previous study, complete the Baseline RUD-Lite, and receive study 
drug during the baseline visit.  Subjects that enroll greater than one week of completion from the previous blinded study will be required to complete ALL baseline assessments.  
All assessments are to be performed PRIOR to investigational drug administration. 
2 The medical history to be taken at baseline will be an update to the medical history taken during the screening and baseline visits of the previous study.  Any AEs that occur after 
the informed consent is signed and before the first dose of investigational drug is taken are to be recorded in the updated medical history and NOT in the AEs log.   
3 The physical examination performed on Week 2, Month 1, Month 3, Month 6, Month 9, Month 12 and every 6 months thereafter will be an update to the full physical 
examination conducted during either the last visit of the previous study or at Baseline of this study.  
 

ACADIA Pharmaceuticals Inc. 
 
Page 18 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
 
Baseline 
(Day 1) 
 Week 2 
(Day 14 ± 
3 days) 
 Month 1 
(Day 28 ± 
3 days) 
Month 3 
Day 84 
+ 7days 
Month 6 
Day 168 
+ 7days 
Month 9 
Day 252 
+ 7days 
Month 12 
(Day 336 ± 7 days) 
AND 
every 6 months 
thereafter 
(168 days ± 7 days) 
End-of-Study 
(if subject 
withdraws or 
is terminated 
from the 
study) 
SAPS5 
 
 
X 
 
 
 
 
 
UPDRS Parts II & III6 
 
X 
X 
X 
X 
X 
X 
X 
CGI-S and CGI-I7 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Events8 
X 
X 
X 
X 
X 
X 
X 
X 
RUD Lite1, 9 
X 
 
 
 
 
 
X 
X 
Prior/Con Meds 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Drug 
Administration10 
X 
X 
X 
X 
X 
X 
X 
 
 
4 Plasma samples for determination of pimavanserin levels are to be taken PRIOR to investigational drug administration on study days; on study visit days the subject should NOT 
take the day’s dose of investigational drug at home.  They should wait until they are at the clinical site. 
5 Scale for the Assessment of Positive Symptoms (SAPS) may be administered by a Central Rater Service, 
 
6 Unified Parkinson’s Disease Rating Scale (UPDRS) 
7 Clinical Global Impression scale-Severity (CGI-S) and Clinical Global Impression scale-Improvement (CGI-I) 
 8 Any adverse event that occurs after signing the ICF and before the first dose of investigational drug is to be recorded in the updated Medical History taken on the Baseline visit 
(Day 1).  
9 Subjects will complete the Baseline RUD-Lite at the Baseline Visit and the Follow Up Visit at subsequent visits, where noted. 
10 Investigational drug is to be taken daily; on study visit days subjects should NOT take the day’s dose at home but  should wait until they are at the site and have had blood drawn 
for pimavanserin plasma level determination before taking the day’s dose. 

ACADIA Pharmaceuticals Inc. 
 
Page 19 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
3.6.2. 
Evaluations by Visit 
An outline of study procedures and evaluations by visit and/or Study Day is provided below.  
Only subjects who completed the treatment period of a previous blinded study of pimavanserin 
for PDP may enter this study. 
 
3.6.2.1. 
Visit 1 (Baseline – Day 1)  
For each subject who is enrolling in this study, the following procedures are to be performed 
following completion of the previous blinded study: 
 
 Informed Consent 
 Inclusion/Exclusion Criteria 
 Administration of study drug (subject’s must complete all Baseline assessments prior to 
administration of study drug)  
 Medical History, an update to the medical history taken during the screening and baseline 
visits of the previous study 
 Baseline RUD Lite  
 
In addition, the following procedures are to be performed for each subject who is enrolling in 
this study greater than one week and within 28 days following completion of the previous 
blinded study. 
 
 Weight 
 Vital Signs 
 Physical Examination  
 Clinical Laboratory Tests 
 Serum Pregnancy Test, if applicable 
 12-Lead ECG 
 Baseline RUD Lite 
 Adverse events 
 Prior/Concomitant Medications 
3.6.2.2. 
Visit 2 (Study Week 2 - Day 14 ± 3 days) 
 Weight 
 12-Lead ECG 
 Vital Signs  
 Updated Physical Examination 
 Clinical Laboratory Tests 
 Blood sample for determination of pimavanserin plasma concentration  
 Caregiver Burden Scale 
 UPDRS Parts II and III 
 CGI-S and CGI-I 
 Adverse events 
 Concomitant Medications 
 Administration of study drug  

ACADIA Pharmaceuticals Inc. 
 
Page 20 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 
3.6.2.3. 
Visit 3 (Study Month 1 -Day 28 ± 3 days) 
 Weight 
 12-Lead ECG 
 Vital Signs 
 Updated Physical Examination 
 Clinical Laboratory Tests 
 Blood sample for determination of pimavanserin plasma concentration  
 Caregiver Burden Scale 
 Scale for the Assessment of Positive Symptoms (SAPS)  
 UPDRS Parts II and III 
 CGI-S and CGI-I 
 Adverse events 
 Concomitant Medications 
 Administration of study drug 
3.6.2.4. 
Visit 4 + [Study Month 3 (Day 84 ± 7 days) and every 3 months thereafter (every 
84 days ± 7 days) until Month 12 (336 days ± 7 days); then every 6 months 
thereafter (every 168 days ± 7 days)] 
 Weight 
 12-Lead ECG 
 Vital Signs 
 Updated Physical Examination 
 Clinical Laboratory Tests 
 Serum pregnancy test, if applicable 
 Blood sample for determination of pimavanserin plasma concentration  
 Caregiver Burden Scale 
 UPDRS Parts II and III 
 CGI-S and CGI-I 
 Follow Up RUD Lite (only for subjects with a previously performed Baseline RUD Lite 
assessment at the Baseline Visit) 
 Adverse events 
 Concomitant Medications 
 Administration of study drug 
3.6.2.5. 
End-of-Study Visit 
Subjects may be removed from this trial at anytime. Upon termination of the subjects’ 
enrollment in this study an End-of-Study visit will be scheduled and the following procedures 
will be conducted: 
 
 Weight 
 12-Lead ECG 
 Vital Signs 
 Physical Examination  
 Clinical Laboratory Tests 

ACADIA Pharmaceuticals Inc. 
 
Page 21 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 Serum Pregnancy Test, if applicable 
 Plasma collection for pimavanserin determination 
 Caregiver Burden Scale 
 UPDRS Parts II and III 
 CGI-S and CGI-I 
 Follow Up RUD Lite (only for subjects with a Baseline RUD Lite assessment at the 
Baseline Visit) 
 Adverse events 
 Concomitant Medications 
 
4. 
SELECTION OF SUBJECTS AND CRITERIA FOR WITHDRAWAL 
4.1 
Selection of Subjects 
The study population is defined as subjects who meet the following criteria: 
 
Inclusion Criteria: 
1. Subject has completed the blinded treatment period of a previous study of pimavanserin 
in PDP within the last 28 days and, who may, in the opinion of the Investigator, benefit 
from therapy with pimavanserin  
2. Subject must have clear sensorium at study entry (i.e., oriented to time, person, and 
place) and thus not be delirious  
3. Female subjects must be of non-childbearing potential (defined as either surgically 
sterilized or at least 1 year post-menopausal) or must agree to use a clinically acceptable 
method of contraception (such as intrauterine device [IUD], diaphragm, or oral, injectable 
[e.g. Depo-Provera] or implantable contraception [e.g. Norplant System]) during the 
study and one month following completion of the study 
4. The subject is willing and able to provide consent  
5. Caregiver is willing and able to provide consent and agrees to accompany the subject to 
all visits 
 
Exclusion Criteria: 
1. Subject has current evidence of a clinically significant concurrent medical illness 
including: severe cardiac disease (recent myocardial infarction, congestive heart failure 
or cardiac syncope), severe pulmonary disease (chronic obstructive pulmonary disease or 
emphysema), renal insufficiency or failure, hepatitis, a recent diagnosis of malignancy 
(excluding basal or squamous cell carcinoma), a serious and or unstable gastrointestinal, 
hematologic or other medical disorder 
2. Subject is using any of the medications prohibited or restricted as described in Appendix 
1 (Prohibited and Restricted Concomitant Medications 

ACADIA Pharmaceuticals Inc. 
Page 22 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
3. Subject is on medications known to prolong the QT interval (as described in Appendix 1)
4. Subject has a baseline electrocardiogram (ECG) with Bazett’s corrected QT (QTcB) of
greater than 460 msec if male or 470 msec if female
5. Subject had an allergy or sensitivity to pimavanserin based on known allergies to drugs of
the same class
6. Subject is judged by the Investigator to be inappropriate for the study
Any waiver of these Inclusion and Exclusion Criteria must be approved in writing by the 
Medical Monitor, on a case-by-case basis, prior to enrolling the subject. 
4.2 
Criteria for Subject Withdrawal 
In accordance with the Declaration of Helsinki and other applicable regulations, a subject has the 
right to withdraw from the study at any time and for any reason without prejudice to his or her 
future medical care. 
Subjects may be discontinued or withdrawn from the study for a number of reasons, including 
but not limited to those listed below: 

Adverse events(s) (serious or non-serious)

Disease progression

Subject’s voluntary withdrawal of consent

The Investigator determines that continuation in the study would be detrimental to a
subject’s well-being because of development of a serious illness, any other significant
change in clinical status, or any other compelling medical reason

Subject fails to comply with protocol requirements

At discretion of Sponsor

Lost to follow-up

Death

Female subject becomes pregnant
If a subject withdraws or is terminated from the study, all efforts must be made to complete the 
procedures for End-of-Study (see Table 1). Furthermore, a reason for withdrawal from the study 
must be provided on the appropriate page of the electronic CRF (eCRF) and in the subject’s 
medical record. If the subject terminated due to an AE, this event must be reported in accordance 
with procedures described in Section 6.2.7 (Adverse Events) of this protocol.  Additional visits 
may be scheduled as medically indicated.  
If a subject is withdrawn due to an AE, the Investigator will arrange for a follow-up visit with the 
subject, as appropriate, until the event has resolved or stabilized. Efforts must be made to follow 
the course of the AE and to document its progress and resolution as described in Section 6.2.7 in 
this protocol.  

ACADIA Pharmaceuticals Inc. 
Page 23 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
For subjects who withdraw consent, further information for inclusion in the clinical trial database 
will not be collected, with the exception of information regarding ongoing AEs at the time of 
withdrawal.  
5.
TREATMENTS ADMINISTERED
5.1 
Identity of Investigational Products 
Table 2 displays the characteristics of the investigational products to be taken during this 
study. Table 2: Investigational Products 
Drug 
Pimavanserin 
Administration Form 
Tablet 
Strength 
20 mg 
Route of administration 
Oral 
5.2 
Dosing 
Forty (40) mg pimavanserin (2 x 20 mg tablets) will be administered orally (i.e., by mouth; po) 
once daily according to the previously described schedule (see Table 1).  The subject should 
make every attempt to take the investigational product in the morning. 
5.3 
Concomitant Therapy 
Concomitant medications should be kept to a minimum during the study.  The Investigator 
should use such medications in accordance with accepted clinical practice and only medications 
essential for subjects’ well-being while enrolled in the study should be administered at the 
Investigator’s discretion. If such medication is deemed essential, subjects should stay on their 
usual medication regimens at stable doses during the entire course of the study if possible. A 
suitable alternative may be used if the drug is on the prohibited list, based on having a 
consultation with the Medical Monitor prior to such a decision. 
Any treatment given, other than the investigational drug, is to be considered a concomitant 
medication. The dosage, time and reason for taking the concomitant medication should be noted 
in the eCRF and medical notes for all subjects. 
As stated above, the Investigator should examine the acceptability of all concomitant therapy not 
explicitly prohibited in this protocol. In order to assure that appropriate concomitant therapy is 
administered, it is essential that subjects be instructed not to take any medication (either self-
administered non-prescription drugs or prescription therapy prescribed by another physician) 
without prior consultation with the Investigator. Accordingly, each subject will be instructed to 
refrain from drinking alcoholic beverages in excess, and using illicit drugs. Use of other drugs 
including any herbal or over-the-counter preparations should be discussed with Investigator.  

ACADIA Pharmaceuticals Inc. 
Page 24 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
5.3.1. 
Prohibited and Restricted Medications 
The restrictions on concomitant medications outlined in Appendix 1 should be followed during 
the course of the study. 
Appendix 1 does not constitute an exhaustive list and any questions regarding prohibited and 
restricted medications should be discussed with the Medical Monitor. 
5.4 
Investigational Drug Handling 
5.4.1. 
Test Article 
Pimavanserin (pimavanserin tartrate) is a white to off-white colored powder.  Pimavanserin will 
be provided as 20 mg strength tablets.  ACADIA Pharmaceuticals will supply the pimavanserin 
tablets.   
5.4.2. 
Drug Packaging 
Study medication will be packaged in individual study kits.  Each kit will contain 12 individually 
labeled bottles.  Each bottle will contain 10 days of study drug (20 tablets.)  
5.4.3. 
Dosage and Administrations 
All subjects will take a single oral dose per day (two tablets per dose) of study medication 
(pimavanserin) every day throughout the study.  On study visit days subjects should NOT take a 
dose at home.  The study drug will be administered at the site once the subject has had blood 
drawn for pimavanserin plasma level determinations.  Subjects should not crush, break, chew, 
or dissolve the tablets. 
5.4.4. 
Receipt of Supplies 
The Investigator and/or study staff is responsible for taking an inventory of each shipment of 
investigational drug received and comparing it with the accompanying Drug Accountability 
Report/Material Shipping Form. The Investigator or study staff member will verify the accuracy 
of the information on the form, sign and date it, and return the form to 
 as 
directed. All investigational drug supplied is for use only in this study and should not be used for 
any other purpose.   
5.4.5. 
Storage of Investigational Drug 
The investigational drug must be kept in a securely locked area with restricted access; and stored 
at room temperature, between 20 and 25º C (68 and 77º F.). Neither the Investigator, nor the 
pharmacist, nor any of his/her designees may provide investigational drug to any person not 
participating in the study.  

ACADIA Pharmaceuticals Inc. 
 
Page 25 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
5.4.6. 
Record of Dispensing 
Accurate recording of all investigational drug administration for individual subjects will be made 
in the appropriate section of the subject’s CRF. A summary of investigational drug 
administration will appear in the Site Investigational Drug Dispensing and Reconciliation Form. 
This form must be updated as subjects are dispensed study drug and contain the following 
information:  
 The initials and subject number to whom the investigational drug was dispensed; 
 The date(s) and quantity of the investigational drug dispensed to the subject; and 
 The initials of the person dispensing the investigational drug.  
 
5.4.7. 
Accountability 
The Investigator or pharmacist will keep accurate records of the quantities of the investigational 
drug product dispensed, used, and returned by each subject to assure the health authority and 
ACADIA that the investigational drug is not dispensed to any person who is not a subject under 
terms and conditions set forth in this protocol. 
 
At the conclusion of the study, final investigational drug reconciliation will be conducted at the 
site. Final investigational drug accountability documentation will be maintained at both the site 
and at ACADIA. Any unused investigational drug will be returned to 
for destruction 
according to local regulations and standard operating procedures (SOPs).  Documentation of 
investigational drug destruction will be recorded and maintained at the site. 
 
6. 
ASSESSMENT OF SAFETY 
6.1 
Primary Objective 
The primary objective of this study will be to assess long-term safety and tolerability of 
pimavanserin in subjects with PDP as measured by AEs, clinical laboratory tests, ECG, vital 
signs, and physical examinations. Furthermore, results of the safety assessments will be used 
during the conduct of the trial to monitor and protect the safety of enrolled subjects. Information 
regarding safety monitoring can be found within the sections below. 
 
6.2 
Description of Safety Assessments 
6.2.1. 
Updated Medical History   
An updated medical history will be obtained at the baseline visit (Study Day 1) for all subjects. 
Family members, caregivers and/or other persons who know the subject may also be 
interviewed, provided the subject consents, in order to obtain updated information about a 
subject’s current medical and psychiatric conditions.  A careful review of medications that were 
started following completion in the previous pimavanserin study should be obtained. 
 

ACADIA Pharmaceuticals Inc. 
 
Page 26 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
6.2.2. 
Physical Examinations and Updated Physical Examinations 
A full physical examination will be performed for those subjects that enroll in this study greater 
than one week following completion of the previous blinded study during the baseline visit by a 
qualified, licensed Doctor of Medicine (MD), Doctor of Osteopathy (DO), or physician assistant 
(PA).  An updated physical examination will be performed for all subjects that enroll in this 
study at the Week 2 visit, Month 1 visit, Month 3 visit, Month 6 visit, Month 9 visit, Month 12 
visit and every 6 month visit thereafter.  At an End-of-Study visit, if a subject withdraws or is 
terminated from the study, a full physical examination will be performed.   
 
A review of systems (ROS) will be included as part of the physical examination procedures. The 
ROS should include:  
 
 Skin, hematological, cardiovascular, pulmonary, gastrointestinal, reproductive, 
neurological, psychiatric, lymphatic, endocrine, musculoskeletal, and/or drug allergies.  
 Particular emphasis should be placed on careful elucidation of hematological, cardiac and 
cardiovascular, neurological and psychiatric conditions. 
 
Findings will be documented in the subject's medical record and on the appropriate eCRF pages. 
Any significant changes from Day 1 (Baseline) are to be recorded during the updated physical 
examination and on the adverse event page for those subjects that enroll greater than one week 
following completion of previous study.  Any significant changes from the last visit of the 
previous study are to be recorded during the updated physical examination and on the adverse 
event page for those subjects that enroll within one week following completion of previous 
study.   
 
6.2.3. 
Weight 
Weight will be measured for those subjects that enroll in this study greater than one week 
following completion of the previous blinded study during the baseline visit, and recorded on the 
appropriate eCRF pages at the Day 1 visit (Baseline).  In addition, weight will be measured for 
all subjects during the Week 2 visit, Month 1 visit, Month 3 visit, Month 6 visit, Month 9 visit, 
Month 12 visit and every 6 month visit thereafter, and if a subject withdraws or is terminated 
from the study, at an End-of-Study visit.   
 
6.2.4. 
Electrocardiogram (ECG) 
Standard 12-lead ECG tracings will be performed on Day 1 (Baseline) for those subjects that 
enroll in this study greater than one week following completion of the previous blinded study.  In 
addition, standard 12-lead ECG tracings will be performed for all subjects the Week 2 visit, 
Month 1 visit, Month 3 visit, Month 6 visit, Month 9 visit, Month 12 visit and every 6 month 
visit thereafter, and if a subject withdraws or is terminated from the study, at an End-of-Study 
visit.   
 

ACADIA Pharmaceuticals Inc. 
 
Page 27 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
6.2.5. 
Vital Signs 
All vital sign measurements will be performed by appropriately qualified and authorized study 
personnel. Vital signs will be measured and recorded on the appropriate CRF pages on Day 1 
(Baseline) for those subjects that enroll in this study greater than one week following completion 
of the previous blinded study.  In addition, vital signs will be measured and recorded for all 
subjects at the Week 2 visit, Month 1 visit, Month 3 visit, Month 6 visit, Month 9 visit, Month 12 
visit and every 6 month visit thereafter, and if a subject withdraws or is terminated from the 
study, at an End-of-Study visit.  
 
Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), will be measured in 
the same arm at each visit by using a manual or automated sphygmomanometer. The results will 
be recorded in millimeters of mercury (mmHg) on the appropriate CRF pages. Pulse rate will be 
measured in the radial artery in the dominant arm for 30 seconds and will be recorded as beats 
per minute (bpm). Respiratory rate (RR) will be measured and recorded in breaths/minute. Oral 
temperature will be measured using a digital thermometer. 
 
Each time vital signs are measured the following procedures for orthostatic BP and pulse rate 
evaluation should be followed: 
 
After the subject is supine for approximately 5 minutes, BP and pulse rate will be measured and 
the subject will then be instructed to rise to a standing position. BP and pulse rate will be again 
measured 1 minute after standing. 
 
Potentially clinically significant orthostatic findings include:  
 
 SBP drop of 20 mmHg or more 
 DBP drop of 15 mmHg or more 
 Pulse rate increase of 20 bpm or more and/or  
 Emergence of clinical symptoms (e.g., dizziness) after standing. 
 
 
6.2.6. 
Clinical Laboratory Tests 
Clinical laboratory evaluations will be performed and recorded on Day 1 (Baseline) for those 
subjects that enroll in this study greater than one week following completion of the previous 
blinded study.  In addition, clinical laboratory evaluations will be performed for all subjects at 
the Week 2 visit, Month 1 visit, Month 3 visit, Month 6 visit, Month 9 visit, Month 12 visit and 
every 6 month visit thereafter, and if a subject withdraws or is terminated from the study, at an 
End-of-Study visit.  
Clinical Chemistry Serum Tests 
 Sodium, Potassium, Chloride, Phosphorus , Calcium, Carbon dioxide, Blood urea 
nitrogen, Creatinine, Uric acid 
 Alanine Aminotransferase, Aspartate Aminotransferase, Gamma-Glutamyl 
Transpeptidase, Alkaline Phosphatase, Total Bilirubin, Lactate Dehydrogenase 

ACADIA Pharmaceuticals Inc. 
 
Page 28 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 Albumin, Total Protein 
 Creatine Kinase/Creatine Phosphokinase 
Hematology Tests 
 Complete blood count including 
o White Blood Cell Count 
o Complete Differential (Relative and Absolute) 
o Hematocrit, Hemoglobin, Red Blood Cells, Platelets 
 Reticulocyte Count 
Urinalysis 
 Blood, Red Blood Cells, White Blood Cells, Protein, Glucose, Ketones, Specific Gravity, 
pH 
Pregnancy Testing 
 Serum pregnancy testing will be performed on Day 1 (Baseline) for those women 
of childbearing potential that enroll in this study greater than one week following 
completion of the previous blinded study.  In addition, serum pregnancy testing 
for all women of childbearing potential will occur at the Month 3 visit, Month 6 
visit, Month 9 visit, Month 12 visit and every 6 month visit thereafter and, if a 
subject withdraws or is terminated from the study, at an End-of-Study Visit. 
 
6.2.6.1. 
Sample Collection and Bioanalytical Processing 
Venous blood samples for clinical laboratory tests will be collected via venipuncture into 
appropriate blood collection vacuum tubes. A central laboratory will analyze all clinical 
laboratory test samples. Blood samples for clinical laboratory tests should be collected and 
processed according to the SOP of the central laboratory. 
 
Blood samples for pharmacokinetic (PK) analysis will be sent to the central laboratory for 
storage and will be forwarded to 
for PK analysis.  Detailed collection and handling 
instructions will be provided in the study laboratory manual.  The date of PK blood collection 
must be recorded in the subject’s CRF. Each label will state the study number, subject number, 
analyte (plasma), and study day of sample. 
 
6.2.6.2. 
Clinically Important Abnormalities 
The following general procedure will be used to determine whether the investigational drug has 
clinically important effects on evaluated parameters: 
 
 Each subject with values of potential clinical importance should receive appropriate 
medical evaluation. To accomplish this, the Investigator and the Medical Monitor will 
each review every subject’s complete laboratory, vital signs and ECG data, all AE 
records, and any other pertinent sections of the CRF. All correspondence related to each 
subject will be documented. 
 

ACADIA Pharmaceuticals Inc. 
 
Page 29 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
Abnormal laboratory test values should be reviewed and interpreted by the Principal Investigator 
or medically qualified Sub-Investigator.  Laboratory test result reports should be signed and 
dated by the reviewing physician(s) for confirmation. Any significant laboratory abnormalities 
that are either serious or unexpected should be promptly reported to the Medical Monitor. The 
diagnosis associated with any clinically significant laboratory abnormality will be recorded as an 
AE on the CRF. If feasible, the AE should be recorded as the underlying abnormality or 
diagnosis (e.g., renal insufficiency) as opposed to the observed deviation in the laboratory result 
(e.g., elevated creatinine). Additional tests and other evaluations required to establish the 
significance or etiology of an abnormal result, or to monitor the course of an AE, may be 
obtained when clinically indicated and with prior approval of the Medical Monitor. In particular, 
if an abnormal result is observed that is not resolved by the final study visit, repeated tests should 
be performed with prior approval until resolution of the abnormality. 
 
6.2.7. 
Adverse Events 
Adverse events will be recorded for all subjects during the Week 2 visit, Month 1 visit, Month 3 
visit, Month 6 visit, Month 9 visit, Month 12 visit and every 6 month visit thereafter, and if a 
subject withdraws or is terminated from the study, at an End-of-Study visit.  
 
Occurrence of AEs after the informed consent is signed and prior to the first administration of 
investigational drug in this study will be recorded as part of the Updated Medical History taken 
on Day 1 (Baseline). Once the first dose of investigational drug is taken on Day 1 any subsequent 
AEs are to be recorded on the CRF page for AEs. 
 
All AEs must be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained or is judged by the investigator to be no longer clinically significant, or until 
the subject is lost to follow-up.  The investigator is responsible for ensuring that follow-up 
includes any supplemental investigations necessary to elucidate as completely as practical the 
nature and/or causality of the AE.  This may include additionally laboratory tests or 
investigations histopathological examinations or consultation with other health care 
professionals. 
 
Investigators are not obliged to actively seek AE information from former study participants.  
However, if the investigator learns of an SAE at any time after a subject has been discharged 
from the study and the event may reasonably be considered related to the use of the study drug, 
the investigator should promptly telephone the Medical Monitor. 
 
6.2.7.1. 
Definitions 
An AE is any untoward medical occurrence or unintended change from the subject’s pre-
treatment condition, including inter-current illness, that occurs during the course of a clinical 
trial after treatment has started, whether considered related to study treatment or not. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product.  
 

ACADIA Pharmaceuticals Inc. 
 
Page 30 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
When possible, AEs should be described by diagnosis and not by symptoms (e.g., “cold” or 
“seasonal allergies” instead of “runny nose”). 
 
The description of each AE should use the following definitions. 
 
Severity 
 
The severity of each AE will be graded on a 3-point scale and reported in detail as indicated on 
the CRF: 
 
 Mild:  easily tolerated, causing minimal discomfort, and not interfering with normal 
everyday activities. 
 Moderate:  sufficiently discomforting to interfere with normal everyday activities. 
 Severe:  incapacitating and/or preventing normal everyday activities. 
 
Relationship to Investigational Drug 
 
The relationship of investigational drug to each AE will be determined by the Investigator by 
using the following definitions: 
 
 Not related:  The event was clearly related to other factors, such as the subject’s clinical 
state, therapeutic interventions, or concomitant medications administered to the subject. 
 Unlikely:  The event was most likely produced by other factors, such as the subject’s 
clinical state, therapeutic interventions, or concomitant medications administered to the 
subject; and did not follow a known response pattern to the investigational drug. 
 Possible:  The event followed a reasonable temporal sequence from the time of 
investigational drug administration; and/or followed a known response pattern to the 
investigational drug; but could have been produced by other factors, such as the subject’s 
clinical state, therapeutic interventions, or concomitant medications administered to the 
subject. 
 Probable:  The event followed a reasonable temporal sequence from the time of 
investigational drug administration; and followed a known response pattern to the 
investigational drug; and could not be reasonably explained by other factors, such as the 
subject’s clinical state, therapeutic interventions, or concomitant medications 
administered to the subject. 
 Highly Probable:  The event followed a reasonable temporal sequence from the time of 
investigational drug administration; and followed a known response pattern to the 
investigational drug; and could not be reasonably explained by other factors, such as the 
subject’s clinical state, therapeutic interventions, or concomitant medications 
administered to the subject; and either occurred immediately following investigational 
drug administration or improved on stopping the investigational drug or reappeared on 
repeat exposure. 
 
Duration 
 
The duration of the AE should be recorded using the following criteria: 

ACADIA Pharmaceuticals Inc. 
Page 31 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 

Start: Date of the first episode of the AE or date of significant sustained worsening in
severity

Stop: Date when AE either ceased permanently or changed in severity
Frequency 
The duration of the AE should be recorded using the following criteria: 

Single:
Experienced once, without recurrence 

Recurrent:
More than one discrete episode with the same severity 
Action Taken with Investigational Drug 

None:
No change in study drug 

Interrupted:
Investigational drug temporarily stopped 

Discontinued: 
Investigational drug discontinued permanently
Therapy 

None:
No new treatment instituted 

Medication:
New treatment initiated as a direct result of AE 

Other:
Other action required 
Outcome 

Ongoing:
AE has not yet stopped 

Resolved, no sequelae:
Subject has fully recovered 
Resolved, with sequelae:
The AE has stopped, but the subject has a residual 
effect directly related to the AE

Death:
The subject died as a result of the AE 

At Death, ongoing:
AE ongoing at time of subject death 
Seriousness 

Not serious:

Serious:
Does not meet the criteria described in Section 6.2.7.2 
Meets the criteria described  in Section 6.2.7.2 
6.2.7.2. 
Serious Adverse Events 
A SAE is any AE that results in any of the following outcomes: 

Results in death

Is life-threatening (i.e., the subject was at risk of death at the time of the event; it does not
refer to an event which hypothetically might have caused death if it were more severe)

Requires inpatient hospitalization or prolongation of existing hospitalization

ACADIA Pharmaceuticals Inc. 
 
Page 32 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 Results in persistent or significant disability/incapacity  
 Is a congenital anomaly or birth defect 
 Is an important medical event that may not be immediately life-threatening or result in 
death or hospitalization but based on appropriate medical judgment may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the outcomes 
listed above. Examples of such events are intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse. 
 
Investigator Reporting Requirements 
All SAEs, whether or not there is a suspected relationship to investigational drug, must be 
reported immediately to 
 (see table below for contact 
details.) In addition, if the Investigator learns of an SAE occurring after a subject withdraws or is 
terminated from the study, but within 30 days after the last administration of the investigational 
drug, he/she should immediately report the event to 
 (see 
contact details below.) 
 
 
Country 
Fax Number 
Phone Number 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
 
 
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The Investigator will complete and submit a SAE Form within 24 hours of discovery for all 
SAEs. The Investigator is obligated to provide information as requested by the clinical monitor 

ACADIA Pharmaceuticals Inc. 
 
Page 33 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
in addition to the information listed on the Serious Adverse Event Form. In general, this will 
include a description of the AE in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible.  
 
In emergency situations, the Investigator should contact the Medical Monitor at 
 
  
 
The reporting of SAEs by ACADIA to the Regulatory Authorities is a regulatory requirement. 
Each Regulatory Authority has established a timetable for reporting SAEs based upon 
established criteria. It is the responsibility of the Investigator to report SAEs to
 
within 24 hours of discovery, to allow for the processing of such 
reports to meet regulatory timelines. 
 
Do not delay in the reporting of any SAE in order to obtain additional information. Any 
additional information, if collected, can be reported to the clinical monitor as a follow-up to the 
initial report. SAEs will be reported using the SAE forms provided as part of the subject’s CRF. 
Please remember to provide the subject identification number, subject initials and other 
appropriate terminology and ensure the narrative is comprehensive and includes a chronological 
description and assessment of the event. 
 
The process for reporting an SAE including those that are considered a consequence of 
investigational drug, of overdose, or associated with pregnancy is as follows: 
 
• Complete an SAE form; 
• Complete the narrative which should be comprehensive and include a chronological 
description and assessment of the event; 
• Complete the fax cover sheet and fax the SAE form to
 
• Ensure the SAE is documented in the source documents and that an AE page is created in the 
subject’s eCRF; 
 
For life-threatening or fatal events, the Investigator (or designee) must call the Medical 
Monitor immediately. All SAEs must be reported within 24 hours of discovery by fax to 
.  If it is not possible to fax the SAE form within the 24-hour 
timeframe, the SAE may be reported by telephone.  All contact details are provided in the 
Investigator Site File/Regulatory Binder. 
 
It is the Investigator’s responsibility to notify the responsible IRB/EC regarding new and 
significant safety information, including expedited safety reports. The Investigator will be 
responsible for forwarding any additional information to the IRB/EC in accordance with specific 
agreements and/or local requirements. 
 
Subjects in this study will be followed for any SAEs and/or unexpected events by the 
Investigator until the abnormal parameter or symptom has resolved or stabilized. These events 

ACADIA Pharmaceuticals Inc. 
Page 34 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
should continue to be reported within 24 hours of discovery, particularly life-threatening or fatal 
events, and the Investigator should continue to provide reports to the IRB/EC, as required. In the 
event of any SAE (other than death), the subject will be instructed to contact the Investigator (or 
designee) using the telephone number provided in the subject information sheet. All subjects 
experiencing an SAE will be seen by the Investigator or designee as soon as is feasible following 
the report of the SAE. 
6.2.8. 
Overdose of Investigational Medicinal Product 
An overdose is a deliberate or inadvertent administration of a treatment at a dose higher than 
specified in the protocol.  It must be reported irrespective of outcome even if toxic effects were 
not observed.  
Any events that are the consequence of investigational drug overdose and which meet the criteria 
for a SAE (Section 6.2.7.2) should be reported via the SAE forms. Any case of overdose must be 
treated according to the current medical practice and followed until resolution or until the 
subject’s condition is considered stable. 
6.2.9. 
Pregnancy 
Any subject who becomes pregnant (with or without AEs) should be reported on the Clinical 
Trial Pregnancy form. This form should be sent to 
 (see 
contact details in Section 6.2.7.2). Any subject who becomes pregnant during the study must 
be withdrawn from treatment and will be followed until delivery or termination of pregnancy. 
Any events that are the consequence of pregnancy and which meet the criteria for serious 
(Section 6.2.7.2) should also be reported via the SAE forms provided and according to the 
directions in Section 6.2.7.2. 
6.2.10. Emergency Treatment 
During and following a subject’s participation in the trial, the Investigator/institution should 
ensure that adequate medical care is provided to a subject for any AEs, including clinically 
significant laboratory values, related to the trial. The Investigator/institution should inform a 
subject when medical care is needed for intercurrent illness(es) of which the Investigator 
becomes aware.  
7.
CLINICAL EVALUATIONS
7.1 
Scale for Assessment of Positive Symptoms (SAPS) 
This scale will be administered to all subjects during Study Month 1 Visit 4. The SAPS 
(Andreasen, 1984) was designed to measure positive psychotic symptoms, especially in 
schizophrenia.  Positive symptoms include delusions, hallucinations, abnormalities in language 
and behavior, and disordered thought processes. Two of the SAPS subscales, Hallucinations and 
Delusions, will be used in this trial (see Appendix 3). The selection of these domains is based 

ACADIA Pharmaceuticals Inc. 
Page 35 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
principally on their relevance to the specific symptomatology of the PDP population, their utility, 
as demonstrated in a previous study of pimavanserin in PDP subjects (ACP-103-006) for 
assessing the severity (reflective of frequency and duration) of these symptoms, and their high 
inter-rater reliability.  
At study sites located outside the United States, qualified raters will be trained and certified to 
administer the SAPS.  At U.S. sites, a centralized rating service, 
will conduct the 
SAPS assessment at the Month 1 Visit 4 only.  The centralized rating service is being used to 
control for possible bias in face-to-face ratings, and to obtain a “blinded” rating of subject 
symptom severity and change.  A remote blinded rater (i.e., mental health evaluator) from the 
centralized service will conduct the SAPS using videoconference technology.  The remote rater 
will be blind to the study design, entrance criteria, visit number, and treatment assignment.  The 
videoconferencing technology used to connect the subject with the remote rater will be Polycom 
videoconferencing equipment connected over an IP VPN (Virtual Private Connection). There 
will be no connection or access to or from any other device, including the Public Internet.  These 
combined technologies ensure that the remote assessment is conducted in privacy and allows the 
remote rater to assess all aspects of the SAPS. 
Subjects whose SAPS ratings are being conducted by 
will be asked to give informed 
consent to have their assessments recorded.  The recordings will be used for training and/or 
quality control purposes by
  The recordings can only be listened to and/or viewed 
by the employees or consultants of 
  No other person will have access to the 
recordings, to the extent permitted by law.  Subject names or other identifying information will 
not be used in training records or publications.  A unique code number that is assigned to the 
subjects will identify their recordings.  The recordings will be maintained in a locked area with 
limited access.  The recordings will be erased no later than one (1) year after the study ends.  
Subjects can still participate in the study even if they choose not to have their assessments 
recorded. 
7.2 
Unified Parkinson’s Disease Rating Scale (UPDRS) 
Motor function will be evaluated by completing Parts II and III of the UPDRS assessment.  
Note:  the UPDRS assessments are to be conducted in the “on” state.  This will ensure that noise 
associated with a subject’s “on/off” status does not confound interpretations of the motor 
function data. 
The UPDRS is a comprehensive battery of motor and behavioral indices derived from the 
Columbia Scale (Fahn et al., 1987; Appendix 4), providing explicit rating criteria that have 
undergone considerable testing for reliability.  Parts II and III will be administered to all subjects 
at the Week 2 visit, Month 1 visit, Month 3 visit, Month 6 visit, Month 9 visit, Month 12 visit 
and  every 6 month visit thereafter, and if a subject withdraws or is terminated from the study, at 
an End-of-Study visit.  

ACADIA Pharmaceuticals Inc. 
Page 36 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
7.3 
Clinical Global Impression Scale (CGI) 
The CGI allows the Investigator to determine, in a global sense, how severely psychotic these 
subjects are in the context of other PD subjects using the CGI-S and how much improvement is 
seen using the CGI-I. This instrument is a reliable scale that allows the Investigator to ignore 
baseline dementia, personality traits, and a “reasonable” degree of anxiety that usually 
accompanies clinical motor fluctuations and other peculiar aspects of PD. The CGI scale appears 
in Appendix 5. 
These scales (CGI-S and CGI-I) will be administered to all subjects at the Week 2 visit, Month 1 
visit, Month 3 visit, Month 6 visit, Month 9 visit, Month 12 visit and every 6 month visit 
thereafter, and if a subject withdraws or is terminated from the study, at an End-of-Study visit. 
7.4 
Caregiver Burden Scale 
The Caregiver Burden Scale (Appendix 2) will be administered to the subject’s attending 
caregiver at the Week 2 visit, Month 1 visit, Month 3 visit, Month 6 visit, Month 9 visit, Month 
12 visit and every 6 month visit thereafter, and if a subject withdraws or is terminated from the 
study, at an End-of-Study visit.  This self-administered 22-item questionnaire is commonly used 
in caregivers of the dementia patient population, most specifically in caregivers of subjects with 
Alzheimer’s disease.  Nonetheless, it has been reported to have high reliability in PD (Aarsland 
et al., 1999).  
7.5 
RUD Lite 
Data related to the health economics and burden of illness of PDP are sparse.  In fact, there are 
no instruments specifically developed to capture this information in the PDP patient population.  
The Resource Utilization in Dementia (RUD) instrument was originally developed for use in 
patients with dementia to capture the use of resources by patients during the course of a clinical 
trial (Wimo et al., 1998).  The assessment of both formal and informal resource use of the patient 
and primary caregiver makes it possible to calculate costs from a societal perspective.  The RUD 
and RUD Lite have been used in several completed and ongoing clinical trials of investigational 
drugs, and are the most widely used instruments for the collection of resource use data in 
dementia (Appendix 6). 
The RUD Lite is an adaptation of the full RUD and is designed to decrease the time burden 
associated with completing multiple assessments during the typical clinical study visit.  For the 
purposes of this study, the RUD Lite instrument has been further adapted to make it compatible 
with the PDP patient population.  It is administered as a structured interview with the primary 
caregiver or other person with knowledge about the patient situation.  The validity and reliability 
of the RUD instrument has been investigated in the residential care setting as well as community 
care setting (Wimo & Nordberg, 2007; Wimo et al., 2003a,b).  Its application in other diseases, 
including PDP, has not been studied; however, it has good face validity and is readily adaptable 
for use in other chronic disorders in older age-groups involving a substantial component of 
informal care. 

ACADIA Pharmaceuticals Inc. 
Page 37 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
The RUD Lite assessment contains a Baseline version and a Follow Up Version. Table 1: 
Schedule of Events and Assessments describes which version should be used at the specified 
study visits. 
8.
ASSESSMENT OF PHARMACOKINETICS
Blood samples will be collected at the Week 2 visit, Month 1 visit, Month 3 visit, Month 6 visit, 
Month 9 visit, Month 12 visit and every 6 month visit thereafter, and if a subject withdraws or is 
terminated from the study, at an End-of-Study visit prior to administration of investigational drug 
on those days. Details of the time of administration of the prior day’s dose together with the time 
of sample collection will aid the interpretation of the concentration data. Section 6.2.6.1 includes 
additional information regarding PK sample collection and bioanalytical processing. 
Pharmacokinetic data will be summarized descriptively. If appropriate, data will be further 
stratified by age, gender, and/or other demographic variables. As appropriate, graphic summaries 
of the PK data will be prepared. 
9.
DATA RECORDING, RETENTION, AND MONITORING
9.1 
Case Report Forms 
An electronic CRF will be provided for each subject and will be used to record all the protocol-
required information to be reported on each subject. The Investigator will maintain a log of the 
source documents from which the information on the CRF will be derived. This will include 
identification of any data agreed with ACADIA to be recorded directly in the CRFs, i.e. where 
the CRF will be considered the source of the information. The participants of the study will not 
be identified by name on the CRF or any other study documents to be collected by ACADIA 
and/or designee, but will be identified by a Subject Identification Number and initials. 
All clinical information requested in this protocol will be recorded on the CRFs provided by 
ACADIA and/or designee using legible entries via computer.  All corrections will be captured 
electronically in the audit trail in addition to the date/time stamp and the user id.  
All CRFs must be reviewed and verified for accuracy by the Investigator and signed off. A copy 
(or original) of the CRF will be kept at the Investigator’s site at the completion of the study. 
9.2 
Availability and Retention of Records 
The Investigator and institution must permit authorized representatives of ACADIA and/or 
designee (including monitors and auditors), and the regulatory agency(s) (including inspectors), 
and the IRB direct access to source documents (such as original medical records). Direct access 
includes permission to examine, analyze, verify, and reproduce any records and reports that are 
needed for the evaluation of the study. The Investigator must ensure the reliability and 
availability of source documents from which the information on the CRF was derived. 

ACADIA Pharmaceuticals Inc. 
 
Page 38 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
Investigators are required to maintain all essential study documentation as per ICH Good 
Clinical Practice (GCP). This includes, but is not limited to, copies of signed, dated and 
completed CRFs, documentation of CRF corrections, signed ICFs, subject-related source 
documentation, and adequate records for the receipt and disposition of all investigational drug. 
Investigators should maintain all essential study documentation, for a period of at least two years 
following the last approval of marketing application in an ICH region (U.S., Europe and Japan), 
or until at least two years after the drug investigational program is discontinued, unless a longer 
period is required by applicable law or regulation. Only ACADIA can notify an Investigator 
when any records may be discarded. Investigators should contact ACADIA before destroying 
any files. 
 
9.3 
Quality Control and Quality Assurance 
ACADIA and/or designee representatives and regulatory authority inspectors are responsible for 
contacting and visiting the Investigator for the purpose of inspecting the facilities and, upon 
request, inspecting the various records of the trial (e.g., CRFs and other pertinent data) provided 
that subject confidentiality is respected. 
 
The ACADIA and/or designee monitor is responsible for inspecting the CRFs at regular intervals 
throughout the study to verify adherence to the protocol; completeness, accuracy, and 
consistency of the data; and adherence to local regulations on the conduct of clinical research. 
The monitor should have access to subject medical records and other study-related records 
needed to verify the entries on the CRFs. 
 
The Investigator agrees to cooperate with the monitor to ensure that any problems detected in the 
course of these monitoring visits are resolved. 
 
In accordance with ICH Guidance on GCP and ACADIA’s audit plans, this study may be 
selected for audit. Inspection of site facilities (e.g., pharmacy, drug storage areas, laboratories, 
etc.) and review of study-related records will occur in order to evaluate the trial conduct and 
compliance with the protocol, ICH Guidance on GCP, and applicable regulatory requirements. 
 
9.4 
Subject Confidentiality 
The Investigator must ensure that each subject’s anonymity is maintained as described below. On 
the CRFs or other documents submitted to ACADIA and/or designee, subjects must be identified 
by their initials and a Subject Identification Number only. Documents that are not for submission 
to ACADIA and/or designee (e.g., signed ICFs) should be kept in strict confidence by the 
Investigator in compliance with Federal regulations or other applicable laws or ICH Guidance on 
GCP. 
 
ACADIA and/or designee representatives, regulatory authority inspectors and IRB 
representatives who obtain direct access to source documents should also respect subject 
confidentiality, taking all reasonable precautions in accordance with applicable regulatory 
requirements to maintain the confidentiality of subjects’ identities. 

ACADIA Pharmaceuticals Inc. 
 
Page 39 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
10. 
STATISTICAL PLAN  
Statistical methods will be documented in detail in a Statistical Analysis Plan to be reviewed and 
approved by ACADIA before any planned database locks. 
10.1 
General Statistical Methods  
All analyses will be performed using SAS V8 (SAS Institute, Inc., Cary, North Carolina). 
Validation and quality control of the tables, listings and figures containing the results of the 
statistical analysis of the data from this study will follow appropriate SOPs. 
10.2 
Study Subjects 
10.2.1. Analysis Population(s) 
The safety population will consist of all subjects who were enrolled in this study and received at 
least one treatment application. The safety population will be used for all safety analyses. 
10.2.2. Subject Accountability and Subject Disposition  
Study enrollment by center will be summarized by the number and percentage of subjects who 
completed the study and those who withdrew early will be presented. A breakdown of the 
corresponding reasons for early withdrawal from study will be provided. 
11. 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
Demographic variables include: age, sex, race, and weight.  Other baseline characteristics 
include medical history.     
12. 
SAFETY ANALYSIS 
12.1 
Adverse Events 
All AEs will be coded using the MedDRA coding dictionary. Events will be classified by body 
system and preferred term. All AEs for each subject including the same event on several 
occasions will be listed, giving both preferred term and the original term. Subject incidence rates 
of treatment-emergent AEs will be displayed by system organ class. AEs will also be 
summarized by severity and relationship to study drug. Subject incidence rates of serious AEs 
(including deaths) will also be displayed.   
 
12.1.1. Clinical Laboratory Values 
Serum clinical chemistry, hematology and urinalysis results will be classified as normal or 
abnormal.  
 
12.1.2. Vital Signs   
Summary statistics of absolute values and percent change from Day 1 (Baseline)  will be 
provided for BP (DBP and SBP), pulse rate, and RR. All values outside a predefined normal 
range will be flagged in the individual subject data listings. 
 

ACADIA Pharmaceuticals Inc. 
 
Page 40 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
12.1.3. Electrocardiogram 
A 12-lead ECG will be recorded at Day 1 (Baseline) for those subjects that enroll greater than 
one week following completion of the previous study.  All subjects will have an ECG at every 
study visit.  Subjects who terminate early will also have an ECG at the End-of-Study visit.  
 
12.1.4. Physical Examinations 
Subjects who enroll in the study greater than one week following completion of the previous 
study will undergo a full physical examination at Day 1 (Baseline). All subjects in the study will 
undergo an updated physical examination at every study visit.  A full physical examination will 
be conducted for all subjects who withdraw or are terminated from the study at an End-of-Study 
visit.  Physical examination data will be included in data listings and reviewed for any clinically 
significant abnormalities. 
 
12.1.5. Pharmacokinetic Analysis 
Pharmacokinetic data will be summarized descriptively.  If appropriate, data will be further 
stratified by age, gender, and/or other demographic variables.  As appropriate, graphic 
summaries of the PK data will be prepared. 
 
12.2 
Efficacy Analysis 
No formal statistical analysis is currently planned for the clinical rating scales (SAPS, UPDRS, 
CGI-I, CGI-S and Caregiver Burden Scale) recorded in this study; however, results for the safety 
population will be summarized with descriptive statistics at each study visit.    
  
13. 
REGULATORY COMPLIANCE 
13.1 
Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol, the Declaration of Helsinki, ICH 
principles of Good Clinical Practice, and other applicable regulatory requirements. 
 
13.2 
Regulatory Approval 
The Investigator at each site is responsible for obtaining IRB or EC approval for the final 
protocol, sponsor-approved ICF, and any advertisements to recruit subjects. Written approval of 
these documents must be obtained from the committee before any subject is enrolled at a center. 
 
The Investigator is also responsible for the following interactions with the IRB or EC: 
 
 Obtaining IRB or EC approval, as appropriate, for any protocol amendments and ICF 
revisions before implementing the changes; 
 Providing the IRB or EC with any required information before or during the study; 

ACADIA Pharmaceuticals Inc. 
 
Page 41 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 Submitting progress reports to the IRB or EC, as required, during the conduct of the 
study; 
 Requesting re-review and approval of the study, as needed; 
 Providing copies of all IRB or EC re-approvals and relevant communication to ACADIA 
and/or designee; 
 Notifying the IRB or EC of all serious and unexpected AEs related to the investigational 
drug reported by ACADIA and/or designee, as required. 
 
13.3 
Subject Informed Consent 
Prior to any study-related activities, an IRB- or EC-approved ICF (and HIPAA authorization 
where applicable) must be signed and dated by the subject and the caregiver. The Informed 
Consent must at a minimum include the elements of consent described in the ICH guidance on 
GCP and the U.S. Code of Federal Regulations 21CFR§50.25. 
 
The Investigator’s draft Informed Consent must be reviewed and approved by ACADIA and/or 
designee prior to IRB or EC submission The Investigator’s IRB or EC will review and approve 
the study protocol, ICF, HIPAA authorization and any other study document (s) according to 
local regulations. After approval by the IRB or EC committee, the following documentation will 
be sent to ACADIA or designee before the study commences: 
 
 Confirmation of IRB or EC approval of the protocol 
 Confirmation of IRB or EC approval of the ICF 
 Confirmation of IRB or EC approval of the HIPAA authorization 
 
In addition to the written ICF, it is the responsibility of the Investigator to ensure that each 
subject under consideration for inclusion into the study be given a verbal explanation of the 
nature, purpose, risks and requirements of the trial. Subjects must be given an adequate 
opportunity to ask the Investigator questions about any aspects of the trial. Once the subject has 
read the ICF, discussed it with the Investigator, and has agreed to participate, he/she will be 
asked to sign the informed consent (and HIPAA authorization, where applicable). The original, 
signed Informed Consent Form (ICF) and HIPAA authorization will remain at the site and copies 
will be given to the subject. 
 
The subject’s consent is confirmed by the dated signature of the subject and by the dated 
signature of the person conducting the informed consent discussions.   
 
The subject’s caregiver will also be asked to consent to participate in the study.  The Investigator 
will use similar procedures to ensure that the caregiver understands the nature, purpose, risks and 
requirements of the trial.  Caregivers must be given an adequate opportunity to ask the 
Investigator questions about any aspects of the trial prior to signing the ICF. 
 
13.4 
Subject Compensation for Adverse Effects on Health 
ACADIA will adhere to any applicable local regulations regarding Clinical Trial Compensation 
Guidelines to subjects whose health is adversely affected by taking part in the study. 

ACADIA Pharmaceuticals Inc. 
 
Page 42 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 
13.5 
Protocol Amendments and Study Termination 
Protocol amendments must be made only with the prior approval of ACADIA and documented 
approval/favorable opinion of the IRB or EC of an amendment, except where necessary to 
protect the safety, rights, or welfare of subjects. Agreement from the Investigator must be 
obtained for all protocol amendments and amendments to the Informed Consent document. The 
IRB or EC must be informed of all amendments and give approval for any amendments likely to 
affect the safety of the subjects or the conduct of the trial. The Investigator must send a copy of 
the approval letter from the IRB or EC to ACADIA and/or designee.  
 
Both ACADIA and the Investigator reserve the right to terminate the study, according to the 
study contract. The Investigator should notify the IRB or EC in writing of the trial’s completion 
or early termination and send a copy of the notification to ACADIA and/or designee.  
 
13.6 
Finance, Insurance and Indemnity 
Arrangements for finance, insurance and indemnity are delineated in the Clinical Study 
Agreement and/or other separate agreements with the Investigator and/or Institution, as 
applicable. 
 
13.7 
Publication 
All publication rights are delineated in the Clinical Study Agreement and/or other separate 
agreements with the Investigator and/or Institution, as applicable. 
 

ACADIA Pharmaceuticals Inc. 
 
Page 43 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
 
14. 
DECLARATION OF INVESTIGATOR 
I confirm that I have read the above protocol. I understand it, and I will work according to the 
moral, ethical, and scientific principles governing clinical research as set out in the principles of 
GCP as described in 21 CFR parts 50, 54, 56, and 312 and according to applicable local 
requirements. 
 
Investigator 
 
 
Date:_____________  Signature: ____________________________________________ 
 
 
Printed Name: ___________________________________ 
 

ACADIA Pharmaceuticals Inc. 
Page 44 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
15.
REFERENCES
Aarsland D, Larsen JP, Lim NG, Janvin C, Karlsen K, Tandberg E, Cummings JL (1999). 
Range of neuropsychiatric disturbances in patients with Parkinson's disease. J Neurol 
Neurosurg Psychiatry; 67(4): 492-496 
Andreason, N., Scale for the Positive Assessment of Positive Symptoms. Iowa City, 
IA, University of Iowa, 1984. 
Chou, KL and Fernandez, HH (2006). Combating psychosis in Parkinson's disease 
patients: the use of antipsychotic drugs. Expert Opin Investig Drugs; 15(4): 339-349. 
Factor, S. A., Feustel, P. J., Friedman, J. H., Comella, C. L., Goetz, C. G., Kurlan, R., Parsa, 
M., Pfeiffer, R., (2003). Longitudinal outcome of Parkinson's disease patients with psychosis. 
Neurology; 60(11): 1756-1761. 
Fahn S, Elton RL, and Members of the UPDRS Development Committee (1987). Unified 
Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, Lieberman A, eds: Recent 
developments in Parkinson's disease. Florham Park, NJ: Macmillan Health Care Information; pp 
153–163. 
Fenelon G, Mahieux F, Huon R, Ziegler M (2000). Hallucinations in Parkinson's 
disease: prevalence, phenomenology and risk factors. Brain; 123: 733-745. 
Guy, W., ECDEU Assessment Manual for Psychopharmacology – Revised 
(DHEW Publ No ADM 76-338). Rockville MD, U.S. Department of Health, Education, 
and Welfare Public Health Service, Alcohol, Drug Abuse, and Mental Health 
Administration, NIMH Psychopharmacology Research Branch, Division of Extramural 
Research Programs, 1976, p. 218-222. 
Marsh, L. Psychosis in Parkinson's disease. Primary Psychiatry, 2005, 12(7). 
Naidu Y, Schapira AHV, Martinez-Martin P et al, International validation of the first 
comprehensive unified motor symptoms scale (NMSS) for Parkinson’s disease (PD). Mov. 
Disord. 21 (Suppl. 15), P1031 S613 (2006). 
Ondo, W., Tintner, R., Voung, K.D., Lai, D., Ringholz, G. Double-blind, placebo-controlled, 
unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in 
Parkinson’s Disease. Mov Disord, 2005, 20(8):958-63. 
Rabey, JM, Prokhorov T, Miniovitz A, Dobronevsky E, Klein C.  Effect of quetiapine in 
psychotic Parkinson’s disease patients:a double-blind labeled study of 3 months’ duration. Mov 
Disord, 2007, 22(3):313-8. 

ACADIA Pharmaceuticals Inc. 
Page 45 
Protocol Amendment #6 ACP-103-015 
June 30, 2010 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. 
Wang, P. S., Schneeweiss, S., Avorn, J., Fischer, M. A., Mogun, H., Solomon, D. H., 
Brookhart, M. A., Risk of death in elderly users of conventional vs. atypical 
antipsychotic medications. N Engl J Med, 2005, 353(22): p. 2335-41. 
Weiner, D. M., Vanover, K. E., Brann, M. R., Meltzer, H. Y., Davis, R. E., 
Psychosis of Parkinson's disease: serotonin 2A receptor inverse agonists as 
potential therapeutics. Curr Opin Investig Drugs, 2003, 4(7): p. 815-9. 
Weintraub, D., and Stern, M.B., Psychiatric Complications in Parkinson Disease. 
Am J Geriat Psych, 2005, 13: 844-851. 
Wimo A, Wetterholm AL, Mastey V, Winblad B.  Evaluation of the resource utilization and 
caregiver time in anti-dementia drug trials – a quantitative battery. In: Wimo A, Karlsson G, 
Jonsson B, Winblad B (eds). The Health Economics of Dementia, 1998. Wiley’s, London, UK. 
Wimo A and Nordberg G (2007). Validity and reliability of assessments of time: Comparisons of 
direct observations and estimates of time by the use of the resource utilization in dementia 
(RUD)-instrument. Arch of Gerontology and Geriatrics; 44: 71-81. 
Wimo A, Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wetterholm AL, Mastey 
V, Haglund A, Zhang R, Miceli R, Chin W, Subbiah P (2003a). An economic evaluation of 
donepezil in mild to moderate Alzheimer’s disease: Results of a 1-year, double-blind, 
randomized trial. Dement Geriatr Cogn Disord; 15: 44-54. 
Wimo A, Winblad B, Stoffler A, Wirth Y, Mobius HJ (2003b). Resource utilization and cost 
analysis of memantine in patients with moderate to severe Alzheimer’s disease. 
Pharmacoeconomics; 21(5): 327-340. 
Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feeling of 
burden.  Gerontologist 1980; 20:649-55. 

ACADIA Pharmaceuticals Inc. 
 
Page 46 
Protocol Amendment #6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
16. 
APPENDICES 
Page 
 
APPENDIX
 
 1:  PROHIBITED AND RESTRICTED CONCOMITANT MEDICATIONS ...................................... 47
APPENDIX
 
 2: CAREGIVER BURDEN SCALE ....................................................................................................... 48
APPENDIX
 
 3: SCALE FOR THE ASSESSMENT OF POSITIVE SYMPTOMS (SAPS) ....................................... 49
APPENDIX
 
 4: UNIFIED PARKINSON’S DISEASE RATING SCALE (UPDRS) .................................................. 62
APPENDIX
 
 5: CLINICAL GLOBAL IMPRESSION (CGI) SCALES ...................................................................... 72
APPENDIX
 
 6: RESOURCE UTILIZATION IN DEMENTIA (RUD LITE) ............................................................. 73
 

ACADIA Pharmaceuticals Inc. 
 
Page 47 
Protocol Amendment # 6 ACP-103-015 
 
June 30, 2010 
 
 
 
Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc.  
 
APPENDIX 1:  PROHIBITED AND RESTRICTED CONCOMITANT MEDICATIONS 
 
The following is an outline of the restrictions on concomitant medications. Any questions 
regarding prohibited and restricted concomitant medications should be discussed with the 
 Medical Monitor. 
 
1. Antipsychotics are prohibited during the first month of the study, including clozapine, 
quetiapine, risperidone, olanzapine, ziprasidone. Addition of any antipsychotic after the 
first month of the study must be discussed with the Medical Monitor. 
 
2. The following medications are prohibited and must have been discontinued no less than 
30 days prior to Study Day 1:  mianserin, mirtazepine, nefazodone, cyproheptadine, 
fluvoxamine, other investigational agents. 
 
3. Centrally-acting anticholinergic medications are prohibited and must have been 
discontinued no less than 2 weeks prior to Study Day 1. These include, and are not 
limited to, benztropine, biperiden, and trihexylphenidyl.  Anticholinergic agents that act 
predominantly on the peripheral nervous system such as tolteradine or oxybutynin, are 
allowed. 
 
4. Use of acetylcholinesterase inhibitors is allowed. 
 
5. Medications that can prolong QT interval are prohibited. These include, and are not 
limited to the following:- 
• Antiarrhythmic drugs including quinidine, procainamide, disopyramide, ajmaline, 
encainide, flecainide, propafenone, amiodarone, sotalol, d-sotalol, bretylium, 
ibutilide, dofetilide, amakalant, semantilide 
• Anticonvulsants including felbamate, fosphenytoin 
• Antidepressants including amitriptyline, nortriptyline, imipramine, desipramine, 
clomipramine, maprotiline, doxepin 
• Antihistamines including diphenhydramine 
• Antimicrobial and antimalarial drugs including erythromycin, clarithromycin, 
ketoconazole, pentamidine, quinine, chloroquine, halofantrine 
• Antipsychotics including thioridazine, chlorpromazine, haloperidol, pimozide, 
ziprasidone, mesoridazine 
• Others including methadone, cocaine 
 
6. Use of amantadine, which may cause QT prolongation, should be discussed with the 
medical monitor.