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 tartrate
Product Code: ACP-103
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Pimavanserin tartrate
CAS Number: 706782-28-7
Current Sponso
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 an appropriate Health Insurance Portability and Accountability Act (HIPAA) authorization form or subject privacy form, if appropriate. - from the subject, if the subject is deemed competent to provide informed consent - from the subject’s legally authorized representative with the subject’s assent, if the subject is deemed not competent to provide informed consent - from the subject’s partner/caregiver during the conduct of the study 2. Male or female, 50 years of age or older 3. Has a diagnosis of probable AD according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) guidelines 4. Meets criteria for agitation according to the International Psychogeriatric Association (IPA) guidelines 5. Has an MRI or CT scan (brain imaging) taken during or subsequent to diagnosis of AD, or during the screening period (prior to Baseline) 6. Has a Mini-Mental State Examination (MMSE) score of 5 to 26 (inclusive) at Screening 7. Has agitation/aggression defined as Neuropsychiatric Inventory (NPI)-agitation/aggression subscore of =4 at both the Screening and Baseline visits with: - severity score of =2, and - frequency score of =2 8. Lives at home or in an assisted living facility. Subjects must have been at their current location for at least 3 weeks prior to Screening and plan to remain at the same location for the duration of the trial. 9. Has a designated study partner/caregiver (e.g., relative, housemate, close personal friend, or professional caregiver) that is in contact with the subject at least 3 times a week on three separate days. The study partner/caregiver must: - 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 PI as sufficiently informed to report accurately on these areas of the subject’s behavioral and functional status. 10. 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. 11. Both subject and study partner/caregiver are willing and able to participate in all scheduled evaluations and complete all required tests 12. If taking antidepressants, has been on a stable dose for at least 4 weeks prior to the Baseline visit and should be expected to remain on a stable dose throughout the trial 13. If taking cholinesterase inhibitors and/or memantine, has been on a stable dose for at least 12 weeks prior to the Baseline visit and should be expected to remain on a stable dose throughout the trial 14. 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, for at least one month prior to randomization, during the study, and one month following completion of the study. Females of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine 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 76 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 230
Exclusion criteria
Exclusion criteria: 1. The agitation/aggression is attributable to concomitant medications, environmental conditions, substance abuse, or active medical or psychiatric condition 2. Has a history of major depressive disorder, recurrent, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) diagnosis and has had a major depressive active episode (within the past year) according to the DSM-5 criteria 3. Treatment with an antipsychotic medication within 2 weeks of Baseline visit or 5 half-lives, whichever is longer 4. Has brain abnormalities seen on an MRI or CT scan (brain imaging) taken during or subsequent to diagnosis of AD, that can be attributed to diseases or processes other than AD, including but not limited to: - multiple lacunar infarcts or evidence of a single prior infarct >1 cm3; - intracranial mass lesion (including but not limited to meningioma [>1 cm3 with evidence of peritumoral edema]); or - glioma, vascular malformation, or macrohemorrhage. 5. Subject or study partner/caregiver has medical condition (e.g., hearing, vision impairments) that would impair the ability to perform the study assessments 6. Using any of the medications prohibited or otherwise restricted (see Protocol Section 5.7, Appendix B, and Appendix C) 7. Subject has had a myocardial infarction within the last 6 months prior to Screening 8. Subject has a known history or symptoms of long QT syndrome 9. Subject has a QRS interval 460 msec at screening OR subject has a QRS interval =120 msec and QTcF is >480 msec at screening 10. Has clinically significant laboratory abnormalities that in the judgment of the Investigator would jeopardize the safe participation of the subject in the study 11. Has a history of a significant psychotic disorder prior to or concomitant with the diagnosis of Alzheimer’s disease including, but not limited to, schizophrenia or bipolar disorder 12. Current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, renal, hematologic, or other medical disorder, including cancer or malignancies that in the judgment of the Investigator would jeopardize the safe participation of the subject in the study 13. Subject is 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 14. Has participated in or is participating in a clinical trial of any investigational drug, device, or intervention, and within 4 weeks (or five half-lives, whichever is longer) of the Baseline visit 15. Subject with sensitivity to pimavanserin or its excipients 16. Subject has previously participated in a clinical study with pimavanserin 17. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of pimavanserin treatment compared with placebo in reducing the severity of agitation and aggression after 12 weeks of treatment.;Secondary Objective: To evaluate the efficacy of pimavanserin compared with placebo on caregiver burden;Primary end point(s): Change from Baseline to Week 12 in Neuropsychiatric Inventory-Clinician rating scale (NPI-C) combined agitation and aggression score.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from Baseline to Week 12 in NPI total caregiver distress score;Timepoint(s) of evaluation of this end point: Week 12 | — |
Countries
Argentina, Chile, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactAD Clinical Trial Information
ACADIA Pharmaceuticals Inc.
Outcome results
None listed