Agitation and Aggression in Alzheimer's Disease MedDRA version: 19.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Nuplazid
Product Name: Pimavanserin
Product Code: ACP-103
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Pimav
Sponsors
ACADIA Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to understand and provide signed informed consent, and must be able to sign and date a request for medical records and/or privacy form, if applicable, according to local regulations. • from the subject, if the subject is deemed competent to provide informed consent • from the subject’s legally authorized representative (LAR) with the subject’s assent, if the subject is deemed not competent to provide informed consent 2. Lives at home or in an assisted living facility 3. Has a designated study partner/caregiver (e.g., relative, housemate, close personal friend, or professional caregiver) who is in contact with the subject at least 3 times a week on 3 separate days. The study partner/caregiver should: • be willing and able to accompany the subject to all clinic visits, • be capable of routinely monitoring and reporting study drug use, • be regarded by the Investigator as sufficiently informed to report accurately on the subject’s behavioral and functional status. 4. The subject’s study partner/caregiver provides written agreement that they understand the study, including the role of the study partner/caregiver and will participate in the study 5. Both subject and study partner/caregiver are fluent in and able to read the local language in which study assessments are administered at the clinical site 6. Both subject and study partner/caregiver are willing and able to participate in all scheduled evaluations and complete all required tests 7. Must complete the Week 12 visit in Study ACP-103-032 while continuing to take his/her assigned dose of blinded study drug 8. If female, must be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) or must agree to use a clinically acceptable method of contraception (e.g., oral, intrauterine device [IUD; diaphragm], injectable, transdermal or implantable contraception) or abstinence during the study, and 1 month following completion of the study. Females of childbearing potential must have a negative urine human chorionic gonadotropin (hCG) pregnancy test at Baseline. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 108 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 324
Exclusion criteria
Exclusion criteria: 1. Is participating in another clinical trial (other than Study ACP-103-032) of any investigational drug, device, or intervention 2. The Investigator determines that enrollment in the study would be detrimental to a subject’s well-being 3. The Investigator becomes aware of an impending and unexpected change in the subject’s living situation (e.g., change in caregiver, change in facility, moving from home to facility, moving from one family member or caregiver’s home to another) that s/he judges may cause a major disruption in the subject’s behaviour 4. Subject or study partner/caregiver has an uncorrected medical condition (e.g., hearing, vision impairments) that would impair the ability to perform the study assessments. 5. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study 6. Subject was significantly non-compliant in Study ACP-103-032 7. Subject has had a QRS interval 460 msec at baseline OR subject has had a QRS interval =120 msec and QTcF is >480 msec at Baseline 8. Has clinically significant laboratory abnormalities that in the judgment of the Investigator would jeopardize the safe participation of the subject in the study 9. Subject has become bedridden or has any significant medical condition that is unstable and that would either: • place the subject at undue risk from study drug or undergoing study procedures; or • interfere with the interpretation of safety or efficacy evaluations performed during the course of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of pimavanserin after 52 weeks of treatment in subjects with probable AD who have symptoms of agitation and aggression.; Secondary Objective: To evaluate the persistence of the effects of pimavanserin treatment on: • Agitation and aggression • Caregiver burden • The clinician’s global assessment of treatment benefit • Other neuropsychiatric symptoms • Cognition • Functional status • Sleep and daytime wakefulness ; Primary end point(s): • Incidence and severity of AEs, serious AEs (SAEs), and withdrawals due to AEs • Changes from Baseline in vital sign measurements, weight, clinical laboratory assessments, physical examinations, and electrocardiograms (ECGs) ; Timepoint(s) of evaluation of this end point: • Adverse events during ACP-103-033 will be recorded through the follow-up safety assessment approximately 30 days after the last dose of open-label study drug. • Physical and neurological examinations will be conducted at Baseline (Visit 1) and Weeks 12 and 52 (i.e., Visits 5 and 10 [EOS/ET]). • Vital signs and weight will be performed at Baseline (Visit 1) and at all scheduled visits. • A 12-lead ECG (single recording) will be performed at Baseline (Visit 1) and at Weeks 4, 12, 28, and 52 (i.e., Visits 3, 5, 7, and 10 [EOS/ET]). • Samples for safety laboratory evaluations will be collected at Baseline (Visit 1) and Weeks 4, 12, 28, and 52 (i.e., Visits 3, 5, 7, and 10 [EOS/ET]). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from Baseline in Cohen-Mansfield Agitation Inventory (CMAI) total score • Change from Baseline in Zarit Burden Interview (ZBI) total score • modified Alzheimer’s Disease Cooperative Study - Clinical Global Impression of Change (mADCS-CGIC) agitation score • Change from Baseline in Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C) combined agitation and aggression domain scores • Change from Baseline in NPI-C total score • Change from Baseline in NPI-C individual domain scores • Change from Baseline in Mini-Mental State Examination (MMSE) score • Change from Baseline in Karolinska Sleepiness Scale (KSS) score • Change from Baseline in CMAI factor scores • Change from Baseline in Alzheimer’s Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) score ; Timepoint(s) of evaluation of this end point: • The CMAI, ZBI and mADCS-CGIC will be performed at Baseline (Day 1) and at all scheduled clinic visits. • The complete NPI-C (i.e., all domains) will be performed at Baseline, Weeks 12, 28, and 52 (i.e., Visits 1, 5, 7, and 10 [EOS/ET]). The agitation and aggression domains of the NPI-C alone will be performed at Weeks 2, 4, and 8 (i.e., Visits 2, 3, and 4). • The MMSE will be administered at Baseline (Visit 1) and at Weeks 4, 8, 12, 20, 28, 36, 44, and 52 (i.e., Visits 3, 4, 5, 6, 7, 8, 9 and 10 [EOS/ET]). • The ADCS-ADL and KSS will be administered at Baseline (Visit 1) and at Weeks 12, 28, and 52 (i.e., Visits 5, 7, and 10 [EOS/ET]). | — |
Countries
Argentina, Chile, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactAD Clinical Trial Information
ACADIA Pharmaceuticals Inc.
Outcome results
None listed