Cobenfy KarXT for Memory Loss

Overseen By Bradley C Lega, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: CYP2D6 inhibitors, CYP3A4 substrates, P-glycoprotein substrates, Antimuscarinic drugs

Disqualifiers: Pregnancy, Hepatic impairment, Renal impairment, others

Compensation: Varies

Number of Visits: 2

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effects of a drug called Cobenfy KarXT on memory by examining changes in brain activity related to memory processing. The study involves patients already scheduled for brain surgery to monitor seizures, allowing researchers to directly measure brain activity. Participants will take part in two sessions: one with the drug and another with a placebo (a harmless pill used for comparison). Researchers will compare brain activity and memory performance between the two sessions. This trial may suit epilepsy patients already undergoing surgery to monitor seizures. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot take certain drugs like strong inhibitors of CYP2D6, sensitive substrates of CYP3A4, narrow therapeutic index substrates of P-glycoprotein, drugs eliminated by active tubular secretion, or antimuscarinic drugs. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Cobenfy KarXT, a combination of two drugs, has been tested for safety in adults with schizophrenia. Most participants in these studies tolerated the drug well. However, individuals with liver issues experienced more side effects, so it is not recommended for those with liver problems.

Cobenfy KarXT has also been studied for another condition, providing some information about its safety. However, this trial focuses on its effects on memory, so safety details might differ. Always consult a doctor to determine if joining this trial is a suitable choice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about COBENFY KarXT for memory loss because it introduces a novel mechanism of action targeting specific brain receptors to potentially enhance memory function. Unlike current treatments, which often focus on neurotransmitter levels, COBENFY KarXT combines two active ingredients, xanomeline and trospium, to work synergistically. This combination aims to improve cognitive abilities with fewer side effects, offering a promising alternative for individuals experiencing memory loss.

What evidence suggests that this trial's treatments could be effective for memory loss?

Research has shown that Cobenfy KarXT, a combination of xanomeline and trospium chloride, may improve thinking and memory. In studies involving individuals with cognitive difficulties, KarXT led to noticeable improvements. Specifically, a study with people who have schizophrenia found that Cobenfy not only alleviated their main symptoms but also enhanced their thinking and memory. Across seven different studies, participants taking KarXT achieved better results than those on a placebo. This trial will compare the effects of Cobenfy KarXT with a placebo to evaluate its potential to support memory and brain function. ^{6 7 8 9 10}

Who Is on the Research Team?

Bradley C Lega, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with epilepsy, in good health apart from their condition. They must be candidates for intracranial electrode evaluation and not have severe liver or kidney issues, bladder problems, untreated glaucoma, or hypersensitivity to the study drugs. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

Able to read, understand, and provide written, dated informed consent prior to screening

In good general health, aside from a history of epilepsy, as ascertained by medical history, physical examination (PE), clinical laboratory evaluations, and ECG

I am between 18 and 75 years old.

Exclusion Criteria

History of hypersensitivity to COBENFY or trospium chloride (angioedema risks)

I have moderate to severe liver problems.

Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results according to the study physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either COBENFY KarXT or placebo and complete episodic memory task sessions

2 days

2 visits (in-person)

Follow-up

Participants are monitored for memory-related changes in brain electrical activity post-intervention

1-3 hours post each intervention

What Are the Treatments Tested in This Trial?

Interventions

• COBENFY KarXT

Trial Overview Researchers are testing Cobenfy KarXT's effects on memory by comparing it with a placebo in epileptic patients undergoing brain surgery. The drug's impact on brain activity and episodic memory processing will be measured during specific tasks.

How Is the Trial Designed?

Group I: COBENFY KarXT (50/20 mg) Experimental Treatment 1 Intervention

Subjects will receive a dose of COBENFY KarXT (50/20 mg). Approximately 2 hours minutes after administration, the participant will then complete an episodic memory task session. If the patient completed the sham session already, this session will take place minimum of 24 hours following the initial session, or at least four half-lives after the first session.

Group II: Placebo Placebo Group 1 Intervention

Subjects will receive a placebo. Approximately 2 hours minutes after administration, the participant will then complete an episodic memory task session. If the patient completed the COBENFY KarXT session already, this session will take place minimum of 24 hours following the initial session, or at least four half-lives after the first session.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Citations

1. nature.com nature.com/articles/s41398-022-02254-9

Effectiveness of KarXT (xanomeline-trospium) for cognitive ... These findings suggest that KarXT may have a separable and meaningful impact on cognition, particularly among patients with cognitive impairment.

2. bbrfoundation.org bbrfoundation.org/content/new-schizophrenia-drug-cobenfy-also-appears-reduce-cognitive-symptoms-patients-who

New Schizophrenia Drug Cobenfy Also Appears to Reduce ... A new study indicated that Cobenfy, a new drug for schizophrenia approved by the FDA in September 2024, may help reduce cognitive impairments in some patients.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41045433/

Efficacy and Safety of KarXT (Xanomeline-Trospium ... Seven trials including 1,316 participants (645 KarXT, 671 placebo) consistently showed that KarXT significantly reduced both positive and ...

4. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ps.20250013

Integrating Cobenfy Into Clinical Practice However, exploratory analyses from the 5-week clinical trials demonstrated significant improvements in cognition only among individuals with ...

5. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-ARISE-Trial-Evaluating-Cobenfy-xanomeline-and-trospium-chloride-as-an-Adjunctive-Treatment-to-Atypical-Antipsychotics-in-Adults-with-Schizophrenia/default.aspx

Cobenfy as an adjunctive treatment to atypical ... Although Cobenfy did not demonstrate a statistically significant improvement as an adjunctive treatment in this trial, the data are encouraging, ...

6. cobenfyhcp.com cobenfyhcp.com/safety/additional-data

Additional safety data for COBENFY in adults with schizophrenia COBENFY is contraindicated in patients with moderate or severe hepatic impairment. COBENFY is not recommended in patients with mild hepatic impairment.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/216158Orig1s000IntegratedR.pdf

216158Orig1s000 - accessdata.fda.gov Inappropriate affect and cognitive deficits are common. • Schizophrenia is associated with increased morbidity and mortality compared to the ...

8. cobenfy.com cobenfy.com/

COBENFY™ (xanomeline and trospium chloride) for ... Increased chance of side effects in people with liver problems (impairment). It is not recommended that people with mild liver problems take COBENFY. Your ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT07228338?aggFilters=status%3A%2Cphase%3A

NCT07228338 | Cholinergic Enhancement of Theta The goal of this study is to learn about the effects of Cobenfy KarXT (xanomeline and trospium chloride) on episodic memory processing, ...

10. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2818047

Efficacy and Safety of Xanomeline-Trospium Chloride in ... This randomized clinical trial evaluates the efficacy and safety of xanomeline-trospium chloride vs placebo in adults with schizophrenia.