A rollover study for subjects that complete Kar-012, to assess Long-term Safety and Tolerability of KarXT in combination with specified atypical antipsychotics in Subjects with Inadequately Controlled Symptoms of Schizophrenia
- Conditions
- SchizophreniaMedDRA version: 20.0Level: PTClassification code 10039626Term: SchizophreniaSystem Organ Class: 10037175 - Psychiatric disordersTherapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2022-001666-35-BG
- Lead Sponsor
- Karuna Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 280
Individuals must meet all the following criteria to be included in the study:
1. Subject is aged 18 to 60 years, at the time of randomization (Visit 3 of Study KAR-012)
2. Subject has successfully completed the treatment period (through Visit 8) of Study KAR-012
3. Subject has been compliant with the procedures in Study KAR-012 (in the Investigator's judgement)
4. Subject has been compliant with their background antipsychotic drug 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.
5. Subject is capable of providing signed eICF before any study assessments will be performed. If local regulations do not allow eICF, then paper ICFs are permitted
6. Subject resides in a stable living situation, in the opinion of the Investigator
7. 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 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.
8. Women of childbearing potential (WOCP), or men whose sexual partners are WOCP, 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 WOCP 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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. 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
2. 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
3. Female subject is pregnant
4. 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 their ability to adhere to the protocol visit schedule or study requirements
5. Risk of violent or destructive behavior as per Investigator’s judgement.
6. Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the study
7. History or high risk of urinary retention, gastric retention, or narrow angle glaucoma as evaluated by the Investigator
8. Subject is taking, or plans to take while in the study, any prohibited
concomitant medication as outlined in APPENDIX 4
9. 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 (PSA) >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.
Subjects already enrolled in the study who do not have available PSA
values from Study KAR-012 for baseline value use in Study KAR-013, will have these assessments at their next clinic visit planned after
reconsenting to determine current eligibility.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the long-term safety and tolerability of adjunctive KarXT in subjects with schizophrenia;Secondary Objective: • Provide additional long-term safety data for monotherapy KarXT in subjects with schizophrenia<br>• Compare the clinical effects (safety and efficacy) of monotherapy KarXT vs adjunctive KarXT after a randomized withdrawal of the background antipsychotic after 6 months of adjunctive therapy in subjects who are stable treatment responders<br>• To evaluate cognition with the Cambridge Neuropsychological Test Automated Battery (CANTAB) in schizophrenia subjects with cognitive dysfunction<br>• To assess steady-state plasma concentrations of xanomeline and trospium during treatment<br>• To evaluate prolactin levels after administration of KarXT;Primary end point(s): • Incidence of treatment-emergent adverse events (TEAEs);Timepoint(s) of evaluation of this end point: The duration of 52 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Incidence of serious TEAEs<br>• Incidence of TEAEs leading to discontinuation of study drug;Timepoint(s) of evaluation of this end point: The duration of 52 weeks