A Phase 3, Randomized, Double-Blind, Placebo-Controlled Relapse Prevention Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated with Alzheimer's Disease (ADEPT-1)
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Trombosis y Anticoagulantes, Linfoma
CENTRO INVESTIGADOR
H.U. de La Princesa
INVESTIGADOR PRINCIPAL
Alba Vieira Campos
FECHA DE APERTURA
Diciembre, 2022
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
1. Is a male or female aged 55 to 90 years, inclusive, at Screening (Visit 1).
10. MMSE score of 6 to 24, inclusive, at Screening (Visit 1). For the rest of the inclusion criteria, please refer to the study protocol.
2. Can understand the nature of the study and protocol requirements and provide a signed informed consent (IC) form before any study assessments are performed. If the subject is deemed not competent to provide IC, both the following requirements for consent must be met. a. The subject's legally acceptable representative (LAR) must provide IC. b. The subject must provide informed assent .
3. Meets clinical criteria for the following disorders: a. Possible or probable AD (APPENDIX 1).
4. Has a Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset of dementia to rule out other central nervous system (CNS) disease that could account for the ementia syndrome, e.g., major stroke, neoplasm, subdural hematoma. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening.
5. Living at the same location for a minimum of six weeks before Screening (Visit 1) with the intention of living at the same location throughout the study.
6. Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified caregiver study partner who, in the investigators judgment, has frequent and sufficient contact with the subject (ie, 10 hours per week) on a regular basis to reliably provide accurate information regarding the participants cognitive, behavioral, and functional status, and is willing to: a. Attend all visits and report on subject's status. The caregiver may delegate a responsible substitute, familiar with the subject, to accompany the subject to Visits 3, 4, 6, and/or 8 ONLY as these visits do not include caregiver scales. b. Oversee subject compliance with medication and study procedures. c. Participate in the study assessments and provide IC to participate in the study.
7. History of psychotic symptoms (meeting International Psychogeriatric Association [IPA] criteria [1]) for at least 2 months prior to Screening (Visit 1). (Subjects may or may not have symptoms of agitation).
8. CGI-S scale with a score 4 (moderate) at Screening (Visit 1) and baseline (Visit 2). CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include allucinations and delusions.
9. AD subjects are required to meet at least one of the following criteria at Screening (Visit 1) and baseline (Visit 2): a. Moderate to severe delusions, defined as NPI-C: Delusions domain score of 2 on two of the eight items OR b. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of 2 on two of the seven items.
10. MMSE score of 6 to 24, inclusive, at Screening (Visit 1). For the rest of the inclusion criteria, please refer to the study protocol.
2. Can understand the nature of the study and protocol requirements and provide a signed informed consent (IC) form before any study assessments are performed. If the subject is deemed not competent to provide IC, both the following requirements for consent must be met. a. The subject's legally acceptable representative (LAR) must provide IC. b. The subject must provide informed assent .
3. Meets clinical criteria for the following disorders: a. Possible or probable AD (APPENDIX 1).
4. Has a Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset of dementia to rule out other central nervous system (CNS) disease that could account for the ementia syndrome, e.g., major stroke, neoplasm, subdural hematoma. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening.
5. Living at the same location for a minimum of six weeks before Screening (Visit 1) with the intention of living at the same location throughout the study.
6. Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified caregiver study partner who, in the investigators judgment, has frequent and sufficient contact with the subject (ie, 10 hours per week) on a regular basis to reliably provide accurate information regarding the participants cognitive, behavioral, and functional status, and is willing to: a. Attend all visits and report on subject's status. The caregiver may delegate a responsible substitute, familiar with the subject, to accompany the subject to Visits 3, 4, 6, and/or 8 ONLY as these visits do not include caregiver scales. b. Oversee subject compliance with medication and study procedures. c. Participate in the study assessments and provide IC to participate in the study.
7. History of psychotic symptoms (meeting International Psychogeriatric Association [IPA] criteria [1]) for at least 2 months prior to Screening (Visit 1). (Subjects may or may not have symptoms of agitation).
8. CGI-S scale with a score 4 (moderate) at Screening (Visit 1) and baseline (Visit 2). CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include allucinations and delusions.
9. AD subjects are required to meet at least one of the following criteria at Screening (Visit 1) and baseline (Visit 2): a. Moderate to severe delusions, defined as NPI-C: Delusions domain score of 2 on two of the eight items OR b. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of 2 on two of the seven items.
CRITERIOS DE EXCLUSIÓN
1. Psychotic symptoms that are primarily attributable to a condition other than the AD causing dementia e.g., schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features.
10. Personal or family history of symptoms of long QT syndrome. For the rest of the exclusion criteria, please refer to the study protocol.
2. History of major depressive episode with psychotic features during the 12 months prior to Screening (Visit 1).
3. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder.
4. Significant or severe medical conditions including pulmonary, hepatic*, renal, hematologic, (eg, obstructive disorders, including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis), endocrine, immunologic, dermatologic, neurologic, cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia),**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. *Participants with any grade of hepatic impairment will be excluded from the study., inclusive of those with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 times of the upper limit of normal (ULN) or total bilirubin > 2 × ULN, or classified as having mild [Child-Pugh Class A], moderate [Child-Pugh Class B], or severe [Child-Pugh Class C] grades of hepatic impairment. **History of unstable hypertension or tachycardia as evidenced by: a. Blood pressure of 160/100 mmHg at screening. b. Heart rate of 100 bpm at screening (confirmed by repeat measurement at the investigators discretion).
5. Significant or severe renal impairment based on a screening cutoff for estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73 m2.
6. History of ischemic stroke within 12 months prior to Screening (Visit 1) or any evidence of hemorrhagic stroke.
7. History of cerebral amyloid angiopathy (CAA), epilepsy, central nervous system (CNS) neoplasm, unstable thyroid function, or unexplained syncope.
8. Any of the following: a. New York Heart Association (NYHA) Class 2 or greater congestive heart failure b. Grade 2 or greater angina pectoris c. History of sustained ventricular tachycardia d. History of ventricular fibrillation e. History of torsade de pointes f. History of implantable cardiac defibrillator.
9. Myocardial infarction within the 6 months prior to Screening (Visit 1).
10. Personal or family history of symptoms of long QT syndrome. For the rest of the exclusion criteria, please refer to the study protocol.
2. History of major depressive episode with psychotic features during the 12 months prior to Screening (Visit 1).
3. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder.
4. Significant or severe medical conditions including pulmonary, hepatic*, renal, hematologic, (eg, obstructive disorders, including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis), endocrine, immunologic, dermatologic, neurologic, cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia),**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. *Participants with any grade of hepatic impairment will be excluded from the study., inclusive of those with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 times of the upper limit of normal (ULN) or total bilirubin > 2 × ULN, or classified as having mild [Child-Pugh Class A], moderate [Child-Pugh Class B], or severe [Child-Pugh Class C] grades of hepatic impairment. **History of unstable hypertension or tachycardia as evidenced by: a. Blood pressure of 160/100 mmHg at screening. b. Heart rate of 100 bpm at screening (confirmed by repeat measurement at the investigators discretion).
5. Significant or severe renal impairment based on a screening cutoff for estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73 m2.
6. History of ischemic stroke within 12 months prior to Screening (Visit 1) or any evidence of hemorrhagic stroke.
7. History of cerebral amyloid angiopathy (CAA), epilepsy, central nervous system (CNS) neoplasm, unstable thyroid function, or unexplained syncope.
8. Any of the following: a. New York Heart Association (NYHA) Class 2 or greater congestive heart failure b. Grade 2 or greater angina pectoris c. History of sustained ventricular tachycardia d. History of ventricular fibrillation e. History of torsade de pointes f. History of implantable cardiac defibrillator.
9. Myocardial infarction within the 6 months prior to Screening (Visit 1).
DESCRIPCIÓN
To evaluate relapse prevention in participants with psychosis associated with AD treated with KarXT compared to placebo
PALABRAS CLAVE
antagonistas de la vitamin k, vitamin k antagonist
