Long-term Safety and Tolerability Assessment of Adjunctive Trospium Chloride and Xanomeline Tartrate in Patients with Inadequately Controlled Schizophrenia Symptoms
- Trial ID
- 2024-510773-20-00
- Protocol
- KAR-013
- Sponsor
- Karuna Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the long-term **safety** and tolerability of adjunctive KarXT in subjects with schizophrenia. This is clinically relevant as it aims to ensure that the treatment is safe for prolonged use in managing inadequately controlled symptoms of schizophrenia, a chronic and severe mental disorder.
Secondary objectives include:
- Providing additional long-term safety data for monotherapy KarXT in subjects with schizophrenia.
- Comparing the clinical effects, including safety and efficacy, of monotherapy KarXT versus adjunctive KarXT after a randomized withdrawal of the background antipsychotic following six months of adjunctive therapy in subjects who are stable treatment responders.
- Evaluating cognition using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in schizophrenia subjects with cognitive dysfunction.
- Assessing steady-state plasma concentrations of xanomeline and trospium during treatment.
- Evaluating prolactin levels after administration of KarXT.
Participants
The clinical trial involves a total of **222 participants** diagnosed with **schizophrenia**. The study population includes both male and female subjects, aged between **18 to 65 years**. Participants were selected based on their successful completion of a prior study (Study KAR-012) and compliance with its procedures, as well as their ability to provide informed consent. The trial includes individuals residing in stable living situations and those who have identified a reliable informant or caregiver to assist with study activities. Participants are required to continue their background antipsychotic drug (APD) regimen from the previous study. The trial population is considered vulnerable, and lifestyle considerations such as the use of effective contraception methods are mandated for women of childbearing potential and their partners. The study aims to assess the long-term safety and tolerability of adjunctive KarXT in this specific population.
Plans and Procedures
The clinical trial is designed to evaluate the long-term safety and tolerability of **KarXT**, a combination of **trospium chloride** and **xanomeline tartrate**, in individuals with inadequately controlled symptoms of **schizophrenia**. This is an open-label extension study, following the completion of a prior trial (Study KAR-012). The trial is structured as a Phase 3 study, focusing on safety and tolerability, and is not classified as a low-intervention trial. Participants will be administered the investigational product in **capsule** form, taken **orally**, with a maximum daily dose of up to 310 mg, depending on the specific formulation used. The maximum treatment period is set at 52 weeks.
The trial will commence with a screening visit to confirm eligibility, based on criteria such as age (18 to 65 years), successful completion of the previous study, and compliance with prior study procedures. Participants must also reside in a stable living situation and have a reliable informant or caregiver to assist with study activities. Following the screening, participants will undergo regular follow-up visits to monitor the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs, as well as any TEAEs leading to discontinuation of the study drug. The primary endpoint is the incidence of TEAEs, while secondary endpoints include the incidence of serious TEAEs and TEAEs leading to discontinuation.
The expected duration of participant involvement is up to 52 weeks, with the study estimated to conclude by April 2026. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or non-compliance with study protocols. Participants are required to use effective contraception methods during the study and for at least 30 days after the last dose of the study drug. The study aims to provide valuable data on the long-term safety profile of KarXT in the target population, contributing to the understanding of its potential therapeutic benefits in managing schizophrenia symptoms.
Treatment
The clinical trial involves the administration of **KarXT**, an experimental medication formulated as a **capsule**. The active substances in KarXT are **trospium chloride** and **xanomeline tartrate**, both of which are of chemical origin. The medication is produced by Karuna Therapeutics Inc. and is administered orally. The trial includes multiple dosing regimens with varying maximum daily doses and total doses over the treatment period. The maximum daily dose for one regimen is 310 mg, with a total dose of 112,840 mg over a 52-week period. Another regimen involves a maximum daily dose of 240 mg, with a total dose of 87,360 mg over the same period. Additional regimens include a maximum daily dose of 140 mg with a total dose of 50,960 mg, and a maximum daily dose of 190 mg with a total dose of 69,160 mg, all administered over 52 weeks.
In this study, KarXT is used as an adjunctive treatment for subjects with inadequately controlled symptoms of **schizophrenia**. The trial aims to assess the long-term safety and tolerability of KarXT. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The pharmaceutical form of the medication remains consistent across all regimens, and no pediatric formulations are involved in this trial. The trial does not involve any orphan drug designations.
Efficacy
The efficacy of the clinical trial involving KarXT, a combination of **trospium chloride** and **xanomeline tartrate**, will be assessed primarily through the incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints include the incidence of serious TEAEs and the incidence of TEAEs leading to discontinuation of the study drug. These endpoints are designed to evaluate the long-term safety and tolerability of adjunctive KarXT in subjects with inadequately controlled symptoms of schizophrenia. The trial is structured as an open-label extension study, allowing for the continuous monitoring of safety parameters over a maximum treatment period of 52 weeks. Data collection will focus on adverse events reported by participants throughout the study duration, ensuring a comprehensive assessment of the drug's safety profile.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject is aged 18 to 65 years (inclusive), at the time of randomization (Visit 3 of Study KAR-012)
- Subject has successfully completed the treatment period (through Visit 8) of Study KAR-012
- Subject has been compliant with the procedures in Study KAR-012 (in the Investigator's judgment)
- Subject has been compliant with their background APD in Study KAR-012 in the opinion of the Investigator and based on subject and informant reporting. Note: Subjects are required to remain on the same appropriate approved APD as in Study KAR-012 and should stay on that same dose throughout the study
- Subject is capable of providing signed ICF before any study assessments will be performed. Subject must be fluent in the language of the ICF to consent
- Subject resides in a stable living situation, in the opinion of the Investigator
- Subject has identified a reliable informant/caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant does not have to be someone responsible for the subject’s physical or psychiatric well-being. As needed, the informant can complete the study visits assessments via phone (as .per local regulations). In Bulgaria, the informant needs to be physically present at all study visits where the Investigator determines that his/her input would be beneficial
- 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 study drug. Sperm donation is not allowed for 30 days after the final dose of the study drug. 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)
Exclusion Criteria
- Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or C-SSRS at Visit 8 in Study KAR-012, as confirmed by the following: a. Subject answers "Yes" to "suicidal ideation" Item 4 (active suicidal ideation with some intent to act, without a specific plan) or Item 5 (active suicidal ideation with a specific plan and intent) on the C-SSRS b. Non-suicidal self-injurious behavior is not exclusionary
- Any clinically significant abnormalities, including any finding(s) from the ECG, or laboratory test at Visit 6, and physical examination, vital signs, at the EOT visit of Study KAR-012 (Visit 8) that the Investigator, in consultation with the Medical Monitor, are considered to jeopardize the safety of the subject
- Female subject is pregnant
- 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 study requirements
- Risk of violent or destructive behavior as per Investigator's judgment
- Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the study
- History or high risk of urinary retention, gastric retention, or narrow angle glaucoma as evaluated by the Investigator
- Subject is taking, or plans to take while in the study, any prohibited concomitant medication as outlined in APPENDIX 4
- For all male subjects only, any one of the following: a. History of bladder stones b. History of recurrent urinary tract infections c. Serum prostate specific antigen >10 ng/mL d. An International Prostate Symptom Score (IPSS) of 5 (almost always) on either item 1, 3, 5, or 6 e. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9 Note: IPSS will be required only for male subjects ≥ 45 years of age. An additional prostate-specific antigen (PSA) result prior to enrollment in study KAR-013 is not required; PSA results captured from the KAR-012 study will suffice.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 07 Mar 2022 | 50 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KarXT | Test | CAPSULE | ORAL | 190 | 52 | PRD11105607 |
KarXT | Test | CAPSULE | ORAL | 310 | 52 | PRD11105609 |
KarXT | Test | CAPSULE | ORAL | 240 | 52 | PRD11105608 |
KarXT | Test | CAPSULE | ORAL | 140 | 52 | PRD11105606 |