Clinical trial NCT06126224: A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-2)
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Psychosis Associated With Alzheimer's Disease
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-11-13
Enrollment: 400
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of KarXT in male and female subjects who are aged 55 to 90 years and have mild to severe Alzheimer's Disease (AD) with moderate to severe psychosis related to AD.

The primary objective of the study is to evaluate the efficacy of KarXT compared with placebo in the treatment of subjects with psychosis associated with AD as measured by the Neuropsychiatric Inventory-Clinician (NPI-C): Hallucinations and Delusions (H+D) score.


Eligibility criteria: Key Inclusion Criteria:

1. Is a male or female aged 55 to 90 years, inclusive, at Screening.
2. Can understand the nature of the trial and protocol requirements and provide informed consent or assent before any study assessments are performed.
3. Meets clinical criteria for Possible AD or Probable AD.
4. Living at the same home or residential assisted-living facility for a minimum of 6 weeks before Screening.
5. Have an identified study partner who should have daily contact (approximately 10 hours a week or more).
6. History of psychotic symptoms (meeting International Psychogeriatric Association criteria) (Cummings 2020) for at least 2 months prior to Screening.
7. CGI-S scale with a score ≥ 4 at Screening and Baseline.
8. AD subjects are required to have NPI-C: Hallucinations and Delusions (H+D) score of ≥ 6 AND meet at least 1 of the following criteria at Screening and Baseline:

   1. Moderate to severe delusions, defined as NPI-C: Delusions domain score of ≥ 2 on 2 of the 8 items OR
   2. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on 2 of the 7 items
9. MMSE score of 8 to 22, inclusive, at Screening.

Key Exclusion Criteria:

1. Psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia.
2. History of major depressive episode with psychotic features during the 12 months prior to Screening.
3. History of bipolar disorder, schizophrenia, or schizoaffective disorder.
4. Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, cardiovascular, or oncologic disease or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results.
5. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator.
6. Prior exposure to KarXT.
7. History of hypersensitivity to KarXT excipients or trospium chloride.
8. Experienced any significant adverse events (AEs) due to trospium.
9. Participation in another clinical study in which the subject received an experimental or investigational drug within 3 months before Screening or has participated in more than 2 clinical studies in the 12 months prior to Screening.

Primary outcomes:
measure: Change from Baseline to End of Treatment in the Neuropsychiatric Inventory-Clinician: Hallucinations and Delusions (NPI-C: H+D) score
timeFrame: Baseline and End of Treatment (up to 14 weeks)
Secondary outcomes:
measure: Change from Baseline to End of Treatment in the Cohen-Mansfield Agitation Inventory (CMAI) score
timeFrame: Baseline and End of Treatment (up to 14 weeks)
measure: Change from Baseline to End of Treatment in the Clinical Global Impressions-Severity (CGI-S) scale
timeFrame: Baseline and End of Treatment (up to 14 weeks)
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Local Institution - 1116
state: Arizona
city: Phoenix
country: United States
facility: Local Institution - 1044
state: Arizona
city: Anaheim
country: United States
facility: Local Institution - 1104
state: California
city: Canoga Park
country: United States
facility: Local Institution - 1119
state: California
city: Encino
country: United States
facility: Local Institution - 1151
state: California
city: Lancaster
country: United States
facility: Local Institution - 1142
state: California
city: Los Alamitos
country: United States
facility: Local Institution - 1117
state: California
city: Sherman Oaks
country: United States
facility: Local Institution - 1103
state: California
city: Walnut Creek
country: United States
facility: Local Institution - 1007
state: California
city: Clermont
country: United States
facility: Local Institution - 1156
state: Florida
city: Cutler Bay
country: United States
facility: Local Institution - 1138
state: Florida
city: Delray Beach
country: United States
facility: Local Institution - 1162
state: Florida
city: Doral
country: United States
facility: Local Institution - 1164
state: Florida
city: Fort Myers
country: United States
facility: Local Institution - 1165
state: Florida
city: Hialeah
country: United States
facility: Local Institution - 1155
state: Florida
city: Hialeah
country: United States
facility: Local Institution - 1107
state: Florida
city: Hialeah
country: United States
facility: Local Institution - 1120
state: Florida
city: Hialeah
country: United States
facility: Local Institution - 1140
state: Florida
city: Homestead
country: United States
facility: Local Institution - 0150
state: Florida
city: Homestead
country: United States
facility: Local Institution - 1145
state: Florida
city: Largo
country: United States
facility: Local Institution - 1127
state: Florida
city: Maitland
country: United States
facility: Local Institution - 1039
state: Florida
city: Maitland
country: United States
facility: Local Institution - 1146
state: Florida
city: Miami Gardens
country: United States
facility: Local Institution - 1126
state: Florida
city: Miami Lakes
country: United States
facility: Local Institution - 1102
state: Florida
city: Miami
country: United States
facility: Local Institution - 1159
state: Florida
city: Miami
country: United States
facility: Local Institution - 1118
state: Florida
city: Miami
country: United States
facility: Local Institution - 1111
state: Florida
city: Miami
country: United States
facility: Local Institution - 1108
state: Florida
city: Miami
country: United States
facility: Local Institution - 1125
state: Florida
city: Miami
country: United States
facility: Local Institution - 1115
state: Florida
city: Miami
country: United States
facility: Local Institution - 1143
state: Florida
city: Miami
country: United States
facility: Local Institution - 1113
state: Florida
city: Miami
country: United States
facility: Local Institution - 1009
state: Florida
city: Miami
country: United States
facility: Local Institution - 1129
state: Florida
city: Miami
country: United States
facility: Local Institution - 1150
state: Florida
city: Miami
country: United States
facility: Local Institution - 1109
state: Florida
city: Miami
country: United States
facility: Local Institution - 1158
state: Florida
city: Miami
country: United States
facility: Local Institution - 1147
state: Florida
city: Miami
country: United States
facility: Local Institution - 1105
state: Florida
city: Miami
country: United States
facility: Local Institution - 1157
state: Florida
city: Okeechobee
country: United States
facility: Local Institution - 1101
state: Florida
city: Orlando
country: United States
facility: Local Institution - 1136
state: Florida
city: Orlando
country: United States
facility: Local Institution - 1112
state: Florida
city: Port Orange
country: United States
facility: Local Institution - 1137
state: Florida
city: Sweetwater
country: United States
facility: Local Institution - 1133
state: Florida
city: Tampa
country: United States
facility: Local Institution - 1041
state: Florida
city: Tampa
country: United States
facility: Local Institution - 1124
state: Florida
city: Tampa
country: United States
facility: Local Institution - 1123
state: Florida
city: Tampa
country: United States
facility: Local Institution - 1110
state: Florida
city: Viera
country: United States
facility: Local Institution - 1131
state: Florida
city: Decatur
country: United States
facility: Local Institution - 1161
state: Georgia
city: Elgin
country: United States
facility: Local Institution - 1148
state: Illinois
city: Marrero
country: United States
facility: Local Institution - 1114
state: Louisiana
city: Rochester Hills
country: United States
facility: Local Institution - 1139
state: Michigan
city: Flowood
country: United States
facility: Local Institution - 1132
state: Mississippi
city: Dayton
country: United States
facility: Local Institution - 1122
state: Ohio
city: Cypress
country: United States
facility: Local Institution - 1106
state: Texas
city: Houston
country: United States
facility: Local Institution - 1163
state: Texas
city: Katy
country: United States
facility: Local Institution - 1154
state: Texas
city: Stafford
country: United States
facility: Local Institution - 1134
state: Texas
city: Hasselt
country: Belgium
facility: Local Institution - 2801
state: Limburg
city: Leuven
country: Belgium
facility: Local Institution - 2802
state: Vlaams Brabant
city: Roeselare
country: Belgium
facility: Local Institution - 2803
state: West-Vlaanderen
city: Providencia
country: Chile
facility: Local Institution - 6002
state: Metropolitana
city: Antofagasta
country: Chile
facility: Local Institution - 6003
city: Las Condes
country: Chile
facility: Local Institution - 6001
city: Hefei
country: China
facility: Local Institution - 7007
state: Anhui
city: Beijing
country: China
facility: Local Institution - 7004
state: Beijing
city: Beijing
country: China
facility: Local Institution - 7005
state: Beijing
city: Chongqing
country: China
facility: Local Institution - 7015
state: Chongqing
city: Guangzhou
country: China
facility: Local Institution - 7008
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 7016
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 7009
state: Guangdong
city: Shenzhen
country: China
facility: Local Institution - 7003
state: Guangdong
city: Nanjing
country: China
facility: Local Institution - 7013
state: Jiangsu
city: Nanchang
country: China
facility: Local Institution - 7012
state: Jiangxi
city: Shanghai
country: China
facility: Local Institution - 7001
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 7011
state: Shanghai
city: Chengdu
country: China
facility: Local Institution - 7002
state: Sichuan
city: Tianjin
country: China
facility: Local Institution - 7019
state: Tianjin
city: Hangzhou
country: China
facility: Local Institution - 7017
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 7010
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 7006
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 7020
state: Zhejiang
city: Wenzhou
country: China
facility: Local Institution - 7018
state: Zhejiang
city: Athina
country: Greece
facility: Local Institution - 4805
state: Attiki
city: Athina
country: Greece
facility: Local Institution - 4803
state: Attiki
city: Chaidari, Athens
country: Greece
facility: Local Institution - 4802
state: Attiki
city: Marousi
country: Greece
facility: Local Institution - 4806
state: Attiki
city: Heraklion
country: Greece
facility: Local Institution - 4801
city: Pécs
country: Hungary
facility: Local Institution - 4601
state: Baranya
city: Budapest
country: Hungary
facility: Local Institution - 4602
city: Miskolc
country: Hungary
facility: Local Institution - 4603
city: Buk-gu
country: Korea, Republic of
facility: Local Institution - 7208
state: Daegu Gwang'yeogsi
city: Seongnam-si
country: Korea, Republic of
facility: Local Institution - 7207
state: Gyeonggido
city: Incheon
country: Korea, Republic of
facility: Local Institution - 7205
state: Incheon Gwang'yeogsi
city: Seongnam-si
country: Korea, Republic of
facility: Local Institution - 7202
city: Seoul
country: Korea, Republic of
facility: Local Institution - 7206
city: Seoul
country: Korea, Republic of
facility: Local Institution - 7203
city: Seoul
country: Korea, Republic of
facility: Local Institution - 7201
city: Saltillo Centro
country: Mexico
facility: Local Institution - 1502
state: Coahuila
city: Monterrey
country: Mexico
facility: Local Institution - 1503
state: Nuevo LEON
city: Monterrey
country: Mexico
facility: Local Institution - 1505
state: Nuevo LEON
city: Culiacan
country: Mexico
facility: Local Institution - 1501
state: Sinaloa
city: Mexico
country: Mexico
facility: Local Institution - 1506
city: Pueblo Libre
country: Peru
facility: Local Institution - 6103
state: Lima
city: Lublin
country: Poland
facility: Local Institution - 4206
state: Lubelskie
city: Lodz
country: Poland
facility: Local Institution - 4207
state: Lódzkie
city: Katowice
country: Poland
facility: Local Institution - 4208
state: Slaskie
city: Bydgoszcz
country: Poland
facility: Local Institution - 4204
city: Katowice
country: Poland
facility: Local Institution - 4205
city: Lodz
country: Poland
facility: Local Institution - 4202
city: Ścinawa
country: Poland
facility: Local Institution - 4201
city: Atakum
country: Turkey
facility: Local Institution - 4702
state: Samsun
city: Eskisehir
country: Turkey
facility: Local Institution - 4701
city: Istanbul
country: Turkey
facility: Local Institution - 4704
city: Izmir
country: Turkey
facility: Local Institution - 4705
city: Izmir
country: Turkey
facility: Local Institution - 4703
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: