Trial Outcomes & Findings for An Open-label Study to Assess the Long-term Safety, Tolerability, Effectiveness, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia (NCT NCT05643170)

NCT ID: NCT05643170

Last Updated: 2024-06-12

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

4 participants

Primary outcome timeframe

From first dose to 28 days post last dose (up to approximately 113 days)

Results posted on

2024-06-12

Participant Flow

Participant milestones

Participant milestones
Measure	KarXT Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Overall Study STARTED	4
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	KarXT Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Overall Study Withdrew from study treatment due to study termination	3
Overall Study Adverse event (AE) that lead to treatment discontinuation	1

Baseline Characteristics

An Open-label Study to Assess the Long-term Safety, Tolerability, Effectiveness, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KarXT n=4 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose to 28 days post last dose (up to approximately 113 days)

Population: All treated participants

Outcome measures

Outcome measures
Measure	KarXT n=4 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation	1 Participants

PRIMARY outcome

Timeframe: At visit 1, 3, 5 (Baseline, week 4, 8), and early termination visit (study day 85)

Population: Modified Intent-to-Treat (mITT) population (All patients who are enrolled and received KarXT through week 8) with available IAQ scores at each timepoint.

The Investigator's Assessment Questionnaire (IAQ) evaluates all health concerns associated with antipsychotic use in patients with schizophrenia or schizoaffective disorder. The IAQ total score is defined as the sum of 10 items (positive symptoms, negative symptoms, somnolence, weight gain, signs and symptoms of prolactin elevation, akathisia, EPS, cognition, energy, and mood) for a total max score of 50; each item is rated on a 5-point Likert scale (1 = Much better, 2 = Slightly better, 3 = About the same, 4 = Slightly worse, and 5 = Much worse) where higher score indicate increased health concerns.

Outcome measures

Outcome measures
Measure	KarXT n=2 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Investigator Assessment Questionnaire (IAQ) Scores Visit 1 (Baseline)	30.00 Score on a scale Standard Deviation 0.000
Investigator Assessment Questionnaire (IAQ) Scores Visit 3 (Week 4)	29.50 Score on a scale Standard Deviation 4.950
Investigator Assessment Questionnaire (IAQ) Scores Visit 5 (Week 8)	32.50 Score on a scale Standard Deviation 2.121
Investigator Assessment Questionnaire (IAQ) Scores Early Termination Visit	31.00 Score on a scale Standard Deviation 1.414

PRIMARY outcome

Timeframe: At visit 1, 2, 3, 5 (baseline, week 2, 4, 8)

Population: Modified Intent-to-Treat (mITT) population (All patients who are enrolled and received KarXT through week 8) with available CGI-S scores at each timepoint.

The Clinical Global Impression - Severity (CGI-S) is a rating scale completed independently by a clinician that is used to measure illness and symptom severity in subjects with mental disorders. It is used to rate the severity of a subject's illness at the time of assessment. The modified CGI-S asks the clinician 1 question: "Considering your total clinical experience, how mentally ill is the subject at this time?" The clinician's answer is rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill subjects.

Outcome measures

Outcome measures
Measure	KarXT n=2 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Clinical Global Impression - Severity of Illness (CGI-S) Scores Visit 1 (Baseline)	3.00 Score on a scale Standard Deviation 0.000
Clinical Global Impression - Severity of Illness (CGI-S) Scores Visit 2 (Week 2)	3.00 Score on a scale Standard Deviation 0.000
Clinical Global Impression - Severity of Illness (CGI-S) Scores Visit 3 (Week 4)	3.00 Score on a scale Standard Deviation 0.000
Clinical Global Impression - Severity of Illness (CGI-S) Scores Visit 5 (Week 8)	3.50 Score on a scale Standard Deviation 0.707

SECONDARY outcome

Timeframe: From first dose to 28 days post last dose (up to approximately 113 days)

Population: All treated participants

An SAE is any untoward medical occurrence that, in the view of either the investigator or Sponsor that: * Results in death. * Is life-threatening. * Results in inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity. * Is a congenital anomaly/birth defect. * Other important medical events

Outcome measures

Outcome measures
Measure	KarXT n=4 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
The Number of Participants With Serious Treatment-Emergent Adverse Events (TESAEs)	1 Participants

SECONDARY outcome

Timeframe: From first dose to 28 days post last dose (up to approximately 113 days)

Population: All treated participants

An Adverse Event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at Screening, worsens during the study, regardless of the suspected cause of the event. AESIs include orthostasis and liver function test (LFT) elevations (inclusive of drug induced liver injury \[DILI\]. Orthostasis will be defined as the patient being symptomatic with at least one of the following differences in orthostatic vitals between sitting position and standing after 2 minutes: * A decrease of systolic BP of 20 mmHg or more. * A decrease in diastolic BP of 10 mmHg or more. * An increase in HR of 30 bpm or more.

Outcome measures

Outcome measures
Measure	KarXT n=4 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
The Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESI)	1 Participants

SECONDARY outcome

Timeframe: At visit 2, 3, 5 (Weeks 2, 4, 8)

Population: Modified Intent-to-Treat (mITT) population (All patients who are enrolled and received KarXT through week 8) with available CGI-I scores at each timepoint.

The Clinical Global Impression - Improvement (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Clinicians are asked: "Compared to the patient's condition at baseline, this patient's \[average\] condition has...?", and they rate as: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.

Outcome measures

Outcome measures
Measure	KarXT n=2 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Clinical Global Impression - Improvement (CGI-I) Score Visit 2 (Week 2)	3.50 Score on a scale Standard Deviation 0.707
Clinical Global Impression - Improvement (CGI-I) Score Visit 3 (Week 4)	4.50 Score on a scale Standard Deviation 0.707
Clinical Global Impression - Improvement (CGI-I) Score Visit 5 (Week 8)	4.50 Score on a scale Standard Deviation 0.707

SECONDARY outcome

Timeframe: Visit 5 (Week 8)

Population: Modified Intent-to-Treat (mITT) population (All patients who are enrolled and received KarXT through week 8) with available MSQ scores at each timepoint.

The Medication Satisfaction Questionnaire (MSQ) is a single-item questionnaire that evaluates satisfaction with antipsychotic medication in schizophrenia patients rated on a 7-point scale (1 = Extremely dissatisfied, 2=Very dissatisfied, 3=Somewhat dissatisfied, 4=Neither satisfied nor dissatisfied, 5=Somewhat satisfied, 6 = Very satisfied, 7 = Extremely satisfied).

Outcome measures

Outcome measures
Measure	KarXT n=2 Participants Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Medication Satisfaction Questionnaire (MSQ) Score	6.00 Score on a scale Standard Deviation 0.000

Adverse Events

KarXT

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	KarXT n=4 participants at risk Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Psychiatric disorders Schizophrenia	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)

Other adverse events

Other adverse events
Measure	KarXT n=4 participants at risk Participants started on a lead-in dose of KarXT 50/20 mg (xanomeline 50 mg/trospium chloride 20 mg), twice daily (BID) Day 1 to Day 7. Followed by the following titration schedule: * Week 1 (Days 1 to 7) - KarXT 50/20 mg, BID. * Week 2 (Days 8 to 14) - KarXT 100/20 mg (xanomeline 100 mg/trospium chloride 20 mg), BID or remain on 50/20 mg, BID. * Week 3 (Days 15 to 21) - KarXT 125/30 mg (xanomeline 125 mg/trospium chloride 30 mg), BID or 100/20 mg, BID. * Weeks 4 to 156 (Days 22 to 1092) - Flexible dosing based on tolerability and clinical response to KarXT 50/20 mg, KarXT 100/20 mg, and KarXT 125/30 mg, BID.
Nervous system disorders Dizziness	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Nervous system disorders Akathisia	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Vascular disorders Orthostatic hypotension	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Psychiatric disorders Abnormal dreams	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Psychiatric disorders Anxiety	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Psychiatric disorders Major depression	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Injury, poisoning and procedural complications Post procedural hypothyroidism	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Gastrointestinal disorders Nausea	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
General disorders Asthenia	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Investigations Red blood cells urine positive	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)
Investigations Blood creatine phosphokinase increased	25.0% 1/4 • From first dose to 28 days post last dose (up to approximately 113 days)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60