Clinical trial NCT06937229: A Study to Evaluate the Long-term Efficacy and Safety of KarXT + KarX-EC for Agitation in Alzheimer's Disease (ADAGIO-3)
Official title: A Phase 3, Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-3)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease
Agitation
Keywords: Agitation
Alzheimer disease
KarXT
KarX-EC
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2025-04-22
Enrollment: 600
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the long-term efficacy and safety of combined formulation of xanomeline tartrate/trospium chloride in an immediate release (IR) capsule (KarXT) and xanomeline enteric capsules (KarX-EC) in participants with agitation associated with Alzheimer's Disease who completed the parent studies CN012-0023 or CN012-0024.


Eligibility criteria: Inclusion Criteria:

* Participants must have completed study CN012-0023 or CN012-0024 per protocol.
* Participants must have one identified caregiver who should have sufficient contact (approximately 10 hours a week or more).

Exclusion Criteria:

* Participants must not have clinically significant cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia), pulmonary, renal, hematologic, GI, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately Week 30
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately Week 30
measure: Number of Participants With TEAEs
timeFrame: Up to approximately Week 30
measure: Number of Participants With Serious AEs (SAEs)
timeFrame: Up to approximately Week 30
measure: Number of Participants With TEAEs Leading to Study Withdrawal
timeFrame: Up to approximately Week 30
measure: Number of Participants With TEAEs Leading to Death
timeFrame: Up to approximately Week 30
measure: Number of Participants with Adverse Events of Special Interest (AESI)
timeFrame: Up to approximately Week 30
measure: Change From Baseline in Barnes Akathisia Rating Scale (BARS)
timeFrame: Up to approximately Week 26
measure: Change From Baseline in Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Up to approximately Week 26
measure: Change From Baseline in Body Weight
timeFrame: Up to approximately Week 26
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Up to approximately Week 26
measure: Number of Participants With Clinically Significant Changes in Orthostatic Vital Sign: Heart Rate (HR)
timeFrame: Up to approximately Week 30
measure: Number of Participants With Clinically Significant Changes in Orthostatic Vital Sign: Blood Pressure (BP)
timeFrame: Up to approximately Week 30
measure: Number of Participants With Clinically Significant Changes in Laboratory Evaluations
timeFrame: Up to approximately Week 30
measure: Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG)
timeFrame: Up to approximately Week 26
measure: Number of Participants With Suicidal Ideations as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to approximately Week 30
measure: Number of Participants With Cognitive Impairment as Assessed by Mini-mental State Examination (MMSE)
timeFrame: Up to approximately Week 26
measure: Number of Participants With Cognitive Impairment as Assessed by 13-item Variation of ADAS-Cog Scale (ADAS-Cog-13)
timeFrame: Up to approximately Week 26
measure: Change From Baseline in the Severity of Benign Prostatic Hyperplasia as Assessed by International Prostate Symptom Score (IPSS)
timeFrame: Up to approximately Week 26
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Local Institution - 2609
state: Arizona
city: Scottsdale
country: United States
facility: Local Institution - 1619
state: Arizona
city: Canoga Park
country: United States
facility: Local Institution - 2620
state: California
city: Long Beach
country: United States
facility: Local Institution - 2625
state: California
city: Long Beach
country: United States
facility: Local Institution - 2607
state: California
city: Pasadena
country: United States
facility: Local Institution - 2613
state: California
city: San Diego
country: United States
facility: Local Institution - 2614
state: California
city: Walnut Creek
country: United States
facility: Local Institution - 1651
state: California
city: Hialeah
country: United States
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state: Florida
city: Miami
country: United States
facility: Local Institution - 1618
state: Florida
city: Miami
country: United States
facility: Local Institution - 1609
state: Florida
city: Miami
country: United States
facility: Local Institution - 1604
state: Florida
city: Orlando
country: United States
facility: Local Institution - 1635
state: Florida
city: Tampa
country: United States
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state: Florida
city: Worcester
country: United States
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state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 2618
state: Michigan
city: Troy
country: United States
facility: Local Institution - 1620
state: Michigan
city: Saint Paul
country: United States
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state: Minnesota
city: Las Vegas
country: United States
facility: Local Institution - 1649
state: Nevada
city: West Long Branch
country: United States
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state: New Jersey
city: Staten Island
country: United States
facility: Local Institution - 2619
state: New York
city: Monroe
country: United States
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state: North Carolina
city: Morehead City
country: United States
facility: Local Institution - 2608
state: North Carolina
city: Blue Ash
country: United States
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state: Ohio
city: Tulsa
country: United States
facility: Local Institution - 1640
state: Oklahoma
city: Columbia
country: United States
facility: Local Institution - 1653
state: South Carolina
city: Carrollton
country: United States
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state: Texas
city: Cypress
country: United States
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state: Texas
city: El Paso
country: United States
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state: Texas
city: Mesquite
country: United States
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state: Texas
city: San Antonio
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state: Texas
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country: United States
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state: Vermont
city: Seattle
country: United States
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state: Washington
city: Spokane
country: United States
facility: Local Institution - 1654
state: Washington
city: Brasília
country: Brazil
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state: Distrito Federal
city: Curitiba
country: Brazil
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state: Paraná
city: Curitiba
country: Brazil
facility: Local Institution - 1052
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city: Porto Alegre
country: Brazil
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city: Rio De Janeiro
country: Brazil
facility: Local Institution - 1050
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country: Brazil
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country: Croatia
facility: Local Institution - 1553
state: Grad Zagreb
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country: Croatia
facility: Local Institution - 1554
city: Split
country: Croatia
facility: Local Institution - 1551
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country: Croatia
facility: Local Institution - 1552
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country: Croatia
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country: Czechia
facility: Local Institution - 2103
state: Jihomoravský Kraj
city: Olomouc
country: Czechia
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state: Olomoucký Kraj
city: Prague
country: Czechia
facility: Local Institution - 2100
state: Praha 6
city: Praha
country: Czechia
facility: Local Institution - 2106
state: Praha 8
city: Chocen
country: Czechia
facility: Local Institution - 2101
city: Plzeň
country: Czechia
facility: Local Institution - 2104
city: Prague
country: Czechia
facility: Local Institution - 2102
city: Praha 10
country: Czechia
facility: Local Institution - 2105
city: Rychnov nad Kneznou
country: Czechia
facility: Local Institution - 2108
city: Toulouse
country: France
facility: Local Institution - 2150
state: Haute-Garonne
city: Villeurbanne
country: France
facility: Local Institution - 2151
state: Rhône
city: Lille
country: France
facility: Local Institution - 2153
city: Limoges
country: France
facility: Local Institution - 2156
city: Paris
country: France
facility: Local Institution - 2152
city: Strasbourg Cedex
country: France
facility: Local Institution - 2155
city: Erbach
country: Germany
facility: Local Institution - 2203
state: Hessen
city: Düsseldorf
country: Germany
facility: Local Institution - 2201
city: Halle /Saale
country: Germany
facility: Local Institution - 2205
city: Westerstede
country: Germany
facility: Local Institution - 2206
city: Patras
country: Greece
facility: Local Institution - 1200
state: Achaḯa
city: Athens
country: Greece
facility: Local Institution - 1205
state: Attiki
city: Athens
country: Greece
facility: Local Institution - 1202
state: Attiki
city: Athens
country: Greece
facility: Local Institution - 0027
city: Athens
country: Greece
facility: Local Institution - 1206
city: Athens
country: Greece
facility: Local Institution - 1203
city: Athens
country: Greece
facility: Local Institution - 1207
city: Ioannina
country: Greece
facility: Local Institution - 1201
city: Thessaloniki
country: Greece
facility: Local Institution - 1204
city: Győr
country: Hungary
facility: Local Institution - 2250
state: Győr-Moson-Sopron
city: Gyöngyös
country: Hungary
facility: Local Institution - 2254
state: Heves
city: Budapest
country: Hungary
facility: Local Institution - 2255
city: Budapest
country: Hungary
facility: Local Institution - 2251
city: Budapest
country: Hungary
facility: Local Institution - 2253
city: Debrecen
country: Hungary
facility: Local Institution - 2252
city: Rishon Le'Tzion
country: Israel
facility: Local Institution - 2304
state: Central
city: Petch Tikva
country: Israel
facility: Local Institution - 2302
state: IL
city: Jerusalem
country: Israel
facility: Local Institution - 2301
city: Netanya
country: Israel
facility: Local Institution - 2303
city: Ramat Gan
country: Israel
facility: Local Institution - 2300
city: Napoli
country: Italy
facility: Local Institution - 2351
state: Campania
city: Roma
country: Italy
facility: Local Institution - 2354
state: Lazio
city: Roma
country: Italy
facility: Local Institution - 2352
state: Lazio
city: Milano
country: Italy
facility: Local Institution - 2353
state: Lombardia
city: Pisa
country: Italy
facility: Local Institution - 2350
state: PI
city: Brescia
country: Italy
facility: Local Institution - 2356
city: Isernia
country: Italy
facility: Local Institution - 2355
city: Roma
country: Italy
facility: Local Institution - 2357
city: Hadano
country: Japan
facility: Local Institution - 1301
state: Kanagawa
city: Kawasaki
country: Japan
facility: Local Institution - 1307
state: Kanagawa
city: Sakai
country: Japan
facility: Local Institution - 1304
state: Osaka
city: Karatsu-shi
country: Japan
facility: Local Institution - 1300
state: Saga-Ken
city: Kanzaki-Gun Yoshinogari-Cho
country: Japan
facility: Local Institution - 1303
state: Saga
city: Bunkyo-ku
country: Japan
facility: Local Institution - 1305
state: Tokyo
city: Fukuoka
country: Japan
facility: Local Institution - 1302
city: Okayama
country: Japan
facility: Local Institution - 1306
city: Incheon
country: Korea, Republic of
facility: Local Institution - 2401
state: Incheon Gwang'yeogsi
city: Seoul
country: Korea, Republic of
facility: Local Institution - 2407
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 2403
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 2406
state: Seoul-teukbyeolsi [Seoul]
city: Deagu
country: Korea, Republic of
facility: Local Institution - 2400
state: Taegu-Kwangyǒkshi
city: Seoul
country: Korea, Republic of
facility: Local Institution - 2402
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Saltillo
country: Mexico
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state: Coahuila
city: Guadajalara
country: Mexico
facility: Local Institution - 1356
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 1350
state: Nuevo León
city: Mexico City
country: Mexico
facility: Local Institution - 1361
city: Mexico City
country: Mexico
facility: Local Institution - 1363
city: Mexico City
country: Mexico
facility: Local Institution - 1360
city: San Luis Potosi
country: Mexico
facility: Local Institution - 1362
city: Tlalnepantla de Baz
country: Mexico
facility: Local Institution - 1352
city: Bydgoszcz
country: Poland
facility: Local Institution - 2454
state: Kujawsko-pomorskie
city: Katowice
country: Poland
facility: Local Institution - 2455
city: Lublin
country: Poland
facility: Local Institution - 2451
city: Lublin
country: Poland
facility: Local Institution - 2452
city: Poznan
country: Poland
facility: Local Institution - 2450
city: Sochaczew
country: Poland
facility: Local Institution - 2453
city: Chorzów
country: Poland
facility: Local Institution - 2456
state: Śląskie
city: Coimbra
country: Portugal
facility: Local Institution - 1401
city: Guimaraes
country: Portugal
facility: Local Institution - 1402
city: Lisboa
country: Portugal
facility: Local Institution - 1404
city: Senhora da Hora
country: Portugal
facility: Local Institution - 1403
city: Torres Vedras
country: Portugal
facility: Local Institution - 1400
city: Bucharest
country: Romania
facility: Local Institution - 1459
state: București
city: Bucuresti
country: Romania
facility: Local Institution - 1450
state: București
city: Bucuresti
country: Romania
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state: București
city: Bucuresti
country: Romania
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state: București
city: Bucuresti
country: Romania
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state: București
city: Bucuresti
country: Romania
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state: București
city: Bucuresti
country: Romania
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state: București
city: Bucuresti
country: Romania
facility: Local Institution - 1458
state: București
city: Bucuresti
country: Romania
facility: Local Institution - 1451
city: Constanta
country: Romania
facility: Local Institution - 1461
city: Iasi
country: Romania
facility: Local Institution - 1457
city: Sanpetru /Brasov
country: Romania
facility: Local Institution - 1460
city: Sibiu
country: Romania
facility: Local Institution - 1462
city: Getxo
country: Spain
facility: Local Institution - 1510
state: Bizkaia
city: Elche (alicante)
country: Spain
facility: Local Institution - 1509
city: Madrid
country: Spain
facility: Local Institution - 1508
city: Madrid
country: Spain
facility: Local Institution - 1505
city: Malaga
country: Spain
facility: Local Institution - 0003
city: Malaga
country: Spain
facility: Local Institution - 1502
city: Pamplona
country: Spain
facility: Local Institution - 1507
city: Salamanca
country: Spain
facility: Local Institution - 1500
city: Sevilla
country: Spain
facility: Local Institution - 1503
city: Terrassa
country: Spain
facility: Local Institution - 1504
city: Valladolid
country: Spain
facility: Local Institution - 1506
city: Zaragoza
country: Spain
facility: Local Institution - 1501
city: London
country: United Kingdom
facility: Local Institution - 2501
state: Greater London
city: Chertsey
country: United Kingdom
facility: Local Institution - 2508
state: Surrey
city: Cambridge
country: United Kingdom
facility: Local Institution - 2502
city: London
country: United Kingdom
facility: Local Institution - 2500
city: Preston
country: United Kingdom
facility: Local Institution - 2505
city: Redruth
country: United Kingdom
facility: Local Institution - 2507
city: Sheffield
country: United Kingdom
facility: Local Institution - 2504
city: Stafford
country: United Kingdom
facility: Local Institution - 2509
city: Wolverhampton
country: United Kingdom
facility: Local Institution - 2503
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: