A study to see how well KarXT is tolerated and how well tolerated it is when taken for long time in participants with psychosis associated with Alzheimer’s disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karuna Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

9 May 2024 → ongoing

Decision date (initial)

2024-07-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Karuna Therapeutics, Inc.

External identifiers

EU CT number

2023-504151-27-00

ClinicalTrials.gov

NCT05980949

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To assess the long-term safety and tolerability of KarXT in subjects with psychosis associated with AD

Conditions and MedDRA coding

Psychosis associated with Alzheimer’s Disease

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Must have completed study KAR-031, KAR-032, CN0120056 or CN0120056
2. 2. Subject was aged 55 to 90 years, inclusive, at the time of enrollment into the parent KAR-031, KAR-032 study or CN0120056 study
3. 3. 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
4. 4. At entry into this study, or any time during the study, if a subject needs to relocate from home or residential assisted-living facility to a nursing home facility, the Sponsor/Medical Monitor must approve the subject’s participation in the study.
5. 5. Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified or proxy caregiver (who spends approximately 10 hours/week with the subject) that is willing to: a. Attend all visits and report on subject’s status b. Oversee subject compliance with medication and study procedures c. Participate in the study assessments and provide IC to participate in the study
6. 6. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP. Sperm donation is not allowed for 30 days after the final dose of the IMP. A female subject is considered to be a WOCBP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). For the definition and list of highly effective methods of contraception, see full protocol/Appendix 1

Exclusion criteria 23

1. 1. 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
2. 10. Personal or family history of symptoms of long QT syndrome as evaluated by the Investigator
3. 11. HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or LFT results
4. 12. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator
5. 13. For males only, any one of the following: a. History of bladder stones; b. History of recurrent urinary tract infections; c. Serum prostate specific antigen (PSA) >10 ng/mL at Screening (Visit 1); d. An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1, 3, 5, or 6; e. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9
6. 14. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
7. 15. Risk of suicidal ideation and behavior during the study as determined by the Investigator’s clinical assessment and/ or C-SSRS at Visit 19 in study KAR-031 or Visit 12 in study KAR-032 or Visit 12 in study CN0120056 as confirmed by the following: a. Answers “Yes” on items 3, 4 or 5 (C-SSRS – ideation) ; b. Answers “Yes” to any of the 5 items (C-SSRS behavior)
8. 16. Urine toxicology screen is positive for substances other than cannabis or benzodiazepines (both cannabis and short- or medium-acting benzodiazepines are allowed in limited quantities during the study) unless approval has been given by the Medical Monitor
9. 17. Unable to taper and discontinue a concomitant medication that would preclude participation in this study
10. 2. 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
11. 3. History of major depressive episode with psychotic features during the 12 months prior to Screening (Visit 1)
12. 4. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder
13. 5. Significant or severe renal impairment based on a screening cutoff for estimated glomerular filtration rate (eGFR) of < 50 mL/min/1.73 m2
14. 6. History of ischemic stroke within 12 months prior to Screening (Visit 1) or any evidence of hemorrhagic stroke
15. 7. History of CAA, epilepsy, CNS neoplasm, unstable thyroid function, or unexplained syncope
16. 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
17. 9. Myocardial infarction within the 6 months prior to Screening (Visit 1)
18. 18. Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), lithium, tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam) a. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening (Visit 1) may be permitted b. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1)
19. 19. Positive test for COVID-19 within 2 weeks before or at Screening (Visit 1); antigen or polymerase chain reaction (PCR) local testing can be done at the discretion of the Investigator
20. 20. Experienced any significant AEs due to trospium, including a known hypersensitivity to trospium
21. 21. Any clinically significant abnormalities, including any finding(s) from the ECG, laboratory tests, physical examination, or vital signs, at the EOT visit of Study KAR-031 (Visit 19), study KAR-032 (Visit 12), or Study CN0120056 (Visit 12) that the Investigator, in consultation with the Medical Monitor, are considered to jeopardize the safety of the subject
22. 22. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements
23. 23. Subjects participating in another investigational drug or device study or planning on participating in another clinical study during the duration of KAR-033.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of TEAEs

Secondary endpoints 1

1. Incidence of serious TEAEs Incidence of TEAEs leading to discontinuation of IMP

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karuna Therapeutics Inc.

Sponsor organisation

Karuna Therapeutics Inc.

Address

Route 206, Province Line Road Province Line Road

City

Princeton

Postcode

08543

Country

United States

Scientific contact point

Organisation

Karuna Therapeutics Inc.

Contact name

GSM-CT

Public contact point

Organisation

Karuna Therapeutics Inc.

Contact name

GSM-CT

Third parties 13

Locations

14 EU/EEA countries · 86 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 2 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 441 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

27 submissions — initial application plus substantial / non-substantial modifications