SchizophreniaPhase 3PENNANTNCT05643170
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
A Phase 3 study testing Xanomeline and Trospium Chloride Capsules in people with Schizophrenia, run by Karuna Therapeutics, Inc., a Bristol Myers Squibb company at 5 sites in United States.
Trial summary
This is a Phase 3b, 3-year, open-label, multi-center study in which patients with DSM-5 diagnosis of schizophrenia whose current medication(s) is not well tolerated and/or clinical symptoms are not well controlled will be switched to receive KarXT. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Xanomeline and Trospium Chloride Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 5 sitesUnited States
- Study dates
- 8 Nov 2022to 8 Mar 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is aged 18 to 65 years, inclusive, at screening.
- Patient can provide informed consent.
- A signed informed consent form (ICF) must be provided before any study assessments are performed.
- Patient must be fluent (oral and written) in the language of the ICF to consent.
- Patient has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM 5 (American Psychiatric Association, 2013) criteria and has been in the continuous care of the clinician or practice for at least 6 months prior to entering the study.
- The patient is dissatisfied with the side effects or general tolerability of their current antipsychotic medication, and for this reason, desires to change medications. Or, the patient is dissatisfied with the overall effectiveness or benefit of their current antipsychotic medication, and for this reason, desires to change medications.
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- The patient has not required psychiatric hospitalization, acute crisis intervention, or other increase in their level of care due to symptom exacerbation within 4 weeks of screening, and in the opinion of the investigator, is psychiatrically stable to be managed in an outpatient setting.
- The patient has a CGI-S score of ≤4 (moderately severe or less) at screening and baseline visits.
- For at least 30 days prior to screening, the patient must have been prescribed and have taken an oral antipsychotic medication daily at a dose and frequency consistent with the drug label.
- Patient has an identified, reliable caregiver/informant that is willing (by informed consent) and able to respond to the ZBI 22 caregiver burden scale at specified visits. If the patient has been the patient of the investigator for ≥6 months and, in the opinion of the investigator, the patient is self-sufficient, then a caregiver/informant may not be necessary.
- Patient resides in a stable living situation and is anticipated to remain in a stable living situation for the duration of the study, in the opinion of the investigator.
- If a woman of childbearing potential (WOCBP) or a man whose sexual partner(s) is a WOCBP, the patient must be willing and able to adhere to the contraception guidelines as defined in Section 12.1 Appendix 1.
Who cannot join
- Any primary DSM-5 disorder diagnosis other than schizophrenia within 12 months before screening. Exclusionary disorders include, but are not limited to, bipolar I or II disorder and schizoaffective disorder. Symptoms of mild mood dysphoria or anxiety are allowed, as long as these symptoms are not the primary focus of treatment.
- The patient has a history of or presence of a clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, is likely to jeopardize the safety of the patient or the validity of the study results.
- Patient has a history of or is at high risk of urinary retention, gastric retention, or narrow angle glaucoma.
- Patient has a history of irritable bowel syndrome (with or without constipation) or constipation requiring treatment for more than 30 days within the last 6 months.
- Clinically significant abnormal finding on the physical examination, medical history, electrocardiogram (ECG), or clinical laboratory results at screening.
- Patient is pregnant, lactating, or less than 3 months postpartum.
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- Patient has tested positive for coronavirus disease 2019 (COVID-19) within 2 weeks of screening and/or baseline or patients who have prolonged symptoms of past infection, long COVID, that, in the opinion of the investigator, may interfere with the interpretation of safety during the study.
- Patient with extreme concerns relating to global pandemics, such as COVID-19, that precludes study participation.
- Patient is currently or recently (within 4 weeks of screening) involuntary hospitalization or incarceration.
- Patient participated in another clinical study in which they received an experimental or investigational drug agent within 30 days prior to screening.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Advanced Discovery Research, LLC
Atlanta, Georgia, 30318
Mid Ohio Behavioral Health
Columbus, Ohio, 43205
Seven Counties Services, Inc.
Louisville, Kentucky, 40203
OnSite Clinical Solutions, LLC
Rock Hill, South Carolina, 29732
Integrated Clinical Research
St. George, Utah, 84770
About this study
Official title: A Multi-center, Open-label Study to Assess the Effectiveness, Long-term Safety, Tolerability, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia
This is a Phase 3b, 3-year, open-label, multi-center study in which patients with DSM-5 diagnosis of schizophrenia whose current medication(s) is not well tolerated and/or clinical symptoms are not well controlled will be switched to receive KarXT.
The primary objectives of the study are to assess the long-term safety and tolerability of KarXT and assess effectiveness, persistence, and durability of effect of KarXT through the Investigator Assessment Questionnaire (IAQ) and Clinical Global Impression - Severity of Illness (CGI-S) scale in patients with a diagnosis of schizophrenia.
The secondary objectives are to further assess the effectiveness using the Clinical Global Impression, Global Improvement (CGI-I), long-term safety and tolerability of KarXT, and evaluation of scores from multiple additional patient scales and assessments throughout the study.
- Conditions
- Schizophrenia
- Being tested
- Xanomeline and Trospium Chloride Capsules
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xanomeline and Trospium Chloride CapsulesDrug
KarXT 50 mg/20 mg BID KarXT 100mg/20 mg BID KarXT 125mg/30 mg BID
| Study group | Role | What they receive |
|---|---|---|
| KarXT | Experimental | Not described Receives: Drug: Xanomeline and Trospium Chloride Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation
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.
Measured: From first dose to 28 days post last dose (up to approximately 113 days)
Investigator Assessment Questionnaire (IAQ) Scores
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.
Measured: At visit 1, 3, 5 (Baseline, week 4, 8), and early termination visit (study day 85)
Clinical Global Impression - Severity of Illness (CGI-S) Scores
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.
Measured: At visit 1, 2, 3, 5 (baseline, week 2, 4, 8)
Secondary outcomes (4)
The Number of Participants With Serious Treatment-Emergent Adverse Events (TESAEs)
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
Measured: From first dose to 28 days post last dose (up to approximately 113 days)
The Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESI)
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.
Measured: From first dose to 28 days post last dose (up to approximately 113 days)
Clinical Global Impression - Improvement (CGI-I) Score
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.
Measured: At visit 2, 3, 5 (Weeks 2, 4, 8)
Medication Satisfaction Questionnaire (MSQ) Score
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).
Measured: Visit 5 (Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2022
- Study start8 Nov 2022
- Primary completion1 Mar 2023
- Study completion8 Mar 2023
Why it stopped: Company's business decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karuna Therapeutics, Inc., a Bristol Myers Squibb company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05643170
- Sponsor's protocol ID
- KAR-014
- Acronym
- PENNANT
- Status last verified
- Jul 2023
- First submitted
- 22 Nov 2022
- Last updated
- 12 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Open-label Study to Assess the Effectiveness, Long-term Safety, Tolerability, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia
- ClinicalTrials.gov ID
- NCT05643170
- Acronym / sponsor ID
- PENNANT / KAR-014
- Conditions
- Schizophrenia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company's business decision.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Karuna Therapeutics, Inc., a Bristol Myers Squibb companyIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2022 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- 8 Mar 2023 (actual)
- First posted
- 8 Dec 2022 (actual)
- Results
- Posted 12 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3b, 3-year, open-label, multi-center study in which patients with DSM-5 diagnosis of schizophrenia whose current medication(s) is not well tolerated and/or clinical symptoms are not well controlled will be switched to receive KarXT.
The primary objectives of the study are to assess the long-term safety and tolerability of KarXT and assess effectiveness, persistence, and durability of effect of KarXT through the Investigator Assessment Questionnaire (IAQ) and Clinical Global Impression - Severity of Illness (CGI-S) scale in patients with a diagnosis of schizophrenia.
The secondary objectives are to further assess the effectiveness using the Clinical Global Impression, Global Improvement (CGI-I), long-term safety and tolerability of KarXT, and evaluation of scores from multiple additional patient scales and assessments throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KarXT | Experimental | Drug: Xanomeline and Trospium Chloride Capsules |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patient is aged 18 to 65 years, inclusive, at screening.
- Patient can provide informed consent.
- Patient has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM 5 (American Psychiatric Association, 2013) criteria and has been in the continuous care of the clinician or practice for at least 6 months prior to entering the study.
- The patient is dissatisfied with the side effects or general tolerability of their current antipsychotic medication, and for this reason, desires to change medications. Or, the patient is dissatisfied with the overall effectiveness or benefit of their current antipsychotic medication, and for this reason, desires to change medications.
- The patient has not required psychiatric hospitalization, acute crisis intervention, or other increase in their level of care due to symptom exacerbation within 4 weeks of screening, and in the opinion of the investigator, is psychiatrically stable to be managed in an outpatient setting.
Key exclusion criteria (10 listed)
- Any primary DSM-5 disorder diagnosis other than schizophrenia within 12 months before screening. Exclusionary disorders include, but are not limited to, bipolar I or II disorder and schizoaffective disorder. Symptoms of mild mood dysphoria or anxiety are allowed, as long as these symptoms are not the primary focus of treatment.
- The patient has a history of or presence of a clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, is likely to jeopardize the safety of the patient or the validity of the study results.
- Patient has a history of or is at high risk of urinary retention, gastric retention, or narrow angle glaucoma.
- Patient has a history of irritable bowel syndrome (with or without constipation) or constipation requiring treatment for more than 30 days within the last 6 months.
- Clinically significant abnormal finding on the physical examination, medical history, electrocardiogram (ECG), or clinical laboratory results at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Xanomeline and Trospium Chloride CapsulesKarXT 50 mg/20 mg BID KarXT 100mg/20 mg BID KarXT 125mg/30 mg BID | Drug | KarXT |
Primary outcome
The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation
Time frame: From first dose to 28 days post last dose (up to approximately 113 days)
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.
Investigator Assessment Questionnaire (IAQ) Scores
Time frame: At visit 1, 3, 5 (Baseline, week 4, 8), and early termination visit (study day 85)
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.
Clinical Global Impression - Severity of Illness (CGI-S) Scores
Time frame: At visit 1, 2, 3, 5 (baseline, week 2, 4, 8)
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.
4 secondary outcomes
The Number of Participants With Serious Treatment-Emergent Adverse Events (TESAEs)
Time frame: From first dose to 28 days post last dose (up to approximately 113 days)
The Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESI)
Time frame: From first dose to 28 days post last dose (up to approximately 113 days)
Clinical Global Impression - Improvement (CGI-I) Score
Time frame: At visit 2, 3, 5 (Weeks 2, 4, 8)
Medication Satisfaction Questionnaire (MSQ) Score
Time frame: Visit 5 (Week 8)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Xanomeline and Trospium Chloride Capsules in people with Schizophrenia, run by Karuna Therapeutics, Inc., a Bristol Myers Squibb company at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation (time frame: From first dose to 28 days post last dose (up to approximately 113 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2024.