Small Molecule · KarXT

Xanomeline/trospium chloride (Cobenfy)

ApprovedKaruna Therapeutics

Oral fixed-dose combination of xanomeline, an M1/M4-preferring muscarinic acetylcholine receptor agonist, and trospium chloride, a peripherally restricted muscarinic antagonist included to offset the peripheral cholinergic side effects of xanomeline (nausea, vomiting, diarrhea, sweating, salivation) without blunting its central activity — trospium is a quaternary ammonium that does not meaningfully cross the blood-brain barrier. Developed by Karuna Therapeutics as KarXT and approved by the FDA on 2024-09-26 as COBENFY (NDA 216158) for schizophrenia in adults: the first antipsychotic acting on muscarinic rather than dopamine D2 receptors, and the first new mechanism of action for schizophrenia in decades. Xanomeline itself is Eli Lilly's LY-246708, which showed antipsychotic-like activity in the 1990s but was abandoned as monotherapy for cholinergic tolerability; Karuna's contribution was the trospium pairing. Bristol Myers Squibb acquired Karuna for $14.0 billion (closed 2024-03-18). Approved in China 2025-12-23 via licensee Zai Lab. Beyond approved adult schizophrenia, the franchise is in Phase 3 for adjunctive schizophrenia (ARISE missed its primary endpoint April 2025), adolescent schizophrenia, relapse prevention, Japan and China registration studies, Alzheimer's disease psychosis (ADEPT program), bipolar I mania, Alzheimer's agitation and cognition, and autism irritability, with a long-acting injectable formulation in Phase 1.

Also known as: KarXT, Cobenfy, xanomeline-trospium, xanomeline and trospium chloride, xanomeline, LY-246708, 131986-45-3, trospium chloride, 10405-02-4, KarX-EC

Data current as of

Key facts

Modality
Small molecule
DEA schedule
Unscheduled
Mechanism
M4 agonist
Highest phase
Approved
Lead indication
Schizophrenia
Developer
Karuna Therapeutics
Trials
19 tracked · 8 recruiting · 1721 sites
Next catalyst
early 2027 — Topline data (Alzheimer's disease psychosis)

Mechanism of action#

Dual-component muscarinic strategy with no direct dopamine D2 blockade. Xanomeline is a muscarinic acetylcholine receptor agonist; per the FDA label its antipsychotic efficacy 'could be due to its agonist activity at M1 and M4 muscarinic acetylcholine receptors in the central nervous system', with the mechanism otherwise not fully established. M4 activation on striatal cholinergic interneurons and M1 activation in cortical/hippocampal circuits are the hypothesized routes to indirect modulation of dopaminergic and glutamatergic signaling. Because muscarinic agonism in the periphery produces nausea, vomiting, diarrhea, sweating and salivation — the tolerability failure mode of xanomeline monotherapy in Eli Lilly's 1990s programs — the combination adds trospium chloride, a quaternary-ammonium pan-muscarinic antagonist that does not meaningfully cross the blood-brain barrier and therefore antagonizes muscarinic receptors primarily in peripheral tissues, offsetting the agonist's peripheral cholinergic effects without blunting central exposure. This architecture (central muscarinic agonist + peripherally restricted antagonist) defined the class that MapLight's ML-007C-MA now follows. In the pivotal EMERGENT trials the combination reduced PANSS total score by 9.6 points (EMERGENT-2) and 8.4 points (EMERGENT-3) versus placebo at week 5 without the weight gain, extrapyramidal symptoms or prolactin elevation characteristic of D2 antagonists.

TargetActionAffinity
M4primaryCHRM4Agonist—ⓘ
M1CHRM1Agonist—ⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
COBENFY oral capsule (xanomeline/trospium chloride 50/20, 100/20, 125/30 mg BID)
Capsules of xanomeline (as tartrate) / trospium chloride: 50 mg/20 mg, 100 mg/20 mg, 125 mg/30 mg. Start 50/20 twice daily for at least 2 days, increase to 100/20 twice daily for at least 5 days, then optionally to 125/30 twice daily based on response and tolerability. Must be taken at least 1 hour before or 2 hours after a meal; capsules must not be opened.
OralTwice dailyt½ 5 h · Tmax 2 h

Development timeline#

2020202220242026TodayPhase 218 Sept 2018 — phase change — EMERGENT-1 (NCT03697252, KAR-004) started: Phase 2, randomized, double-blind, placebo-controlled, 182 hospitalized adults with acute schizophrenia; primary endpoint change in PANSS total at week 5. Positive: -11.6 points vs placebo (published NEJM 2021-02-25). Xanomeline itself had earlier Lilly-era clinical history in the 1990s; this history starts with the KarXT combination.Phase 330 Jun 2027 — upcoming — Topline from ADEPT-4, the second acute-efficacy Phase 3 of Cobenfy in Alzheimer's disease psychosis (NPI-C H+D primary endpoint): among readouts beginning early 2027 and spread across the year.30 Jun 2027 — upcoming — Topline from ADEPT-1, the Phase 3 relapse-prevention (randomized-withdrawal) study of Cobenfy in Alzheimer's disease psychosis: among readouts beginning early 2027 and spread across the year, with a potential interim analysis later in 2026.31 Mar 2027 — upcoming — Topline results from ADEPT-2, the first acute-efficacy Phase 3 of Cobenfy in Alzheimer's disease psychosis (primary endpoint: change in NPI-C Hallucinations and Delusions score), now expected among readouts beginning early 2027.3 Dec 2025 — phase change — ADEPT-2 continuation announcement: BMS identified 'irregularities due to clinical trial execution at a small number of study sites', excluded those sites' patient data from the primary analysis, had an independent party assess the collected data, and per the Data Monitoring Committee's recommendation continued the trial with additional enrollment (BMS remaining blinded). ADEPT-1/-2/-4 readouts guided to end-2026 at that time; on 2026-07-30 (Q2 2026 earnings) guidance moved again to topline readouts beginning early 2027, spread across the year. Phase and status unchanged — recorded because the enrollment extension and readout slips are material program events with no fitting event_type code.20 Mar 2023 — readout (met) — EMERGENT-3 (Phase 3) topline positive: KarXT met the primary endpoint with an 8.4-point reduction in PANSS total score vs placebo at week 5, the third consecutive positive registrational trial.23 Aug 2022 — phase change — ADEPT-1 (NCT05511363, CN012-0026) started per ClinicalTrials.gov: the ADP program opened directly in Phase 3 with a randomized-withdrawal relapse-prevention design (open-label KarXT, then randomization to continue or withdraw; primary endpoint time from randomization to relapse over 38 weeks). Started under Karuna Therapeutics, pre-acquisition.8 Aug 2022 — readout (met) — EMERGENT-2 (Phase 3) topline positive: KarXT met the primary endpoint with a statistically significant 9.6-point reduction in PANSS total score vs placebo at week 5 (p<0.0001), and met key secondary endpoints on PANSS positive, negative and Marder negative-factor subscales.8 Nov 2021 — Licensing deal — Karuna licenses KarXT Greater China rights to Zai Lab ($35M upfront)25 Feb 2021 — readout (met) — EMERGENT-1 (Phase 2) published in NEJM: xanomeline-trospium reduced PANSS total score by 11.6 points more than placebo at week 5 (p<0.001) in 182 hospitalized adults with acute schizophrenia, without D2-antagonist-typical adverse events.16 Dec 2020 — phase change — EMERGENT-2 (NCT04659161, KAR-007) started: first Phase 3, 252 acutely psychotic hospitalized adults, PANSS total at week 5. Topline positive 2022-08-08 (-9.6 points vs placebo, p<0.0001); published in The Lancet 2024-01-13. EMERGENT-3 (NCT04738123) followed in April 2021 and read out positive 2023-03-20 (-8.4 points).Filed (NDA)18 Mar 2024 — Acquisition — Bristol Myers Squibb completes its $14.0 billion acquisition of Karuna Therapeutics29 Nov 2023 — PDUFA date set — FDA accepts the KarXT NDA and sets a PDUFA date of September 26, 202430 Sept 2023 — phase change — Karuna submitted the NDA for KarXT for schizophrenia in adults in September 2023 (exact day not disclosed in the acceptance release; dated month-end as an upper bound). FDA accepted the NDA on 2023-11-29 and set a PDUFA action date of 2024-09-26. Supported by EMERGENT-1/-2/-3 (efficacy) and EMERGENT-4/-5 (long-term safety).30 Sept 2023 — NDA/BLA filed — Karuna submits the KarXT NDA for schizophrenia to the FDAApproved23 Dec 2025 — NMPA approval (China) — China's NMPA approves COBENFY for schizophrenia in adults (via Zai Lab)22 Apr 2025 — readout (missed) — ARISE (Phase 3, adjunctive to atypical antipsychotics) MISSED its primary endpoint: Cobenfy added to an atypical antipsychotic reduced PANSS total score by 2.0 points vs placebo+antipsychotic at week 6, not statistically significant (p=0.11).26 Sept 2024 — phase change — FDA approved COBENFY (xanomeline and trospium chloride) capsules, NDA 216158, for the treatment of schizophrenia in adults, on the PDUFA date. First-in-class muscarinic antipsychotic; openFDA records the original approval as a TYPE 1 (new molecular entity) submission by Bristol-Myers Squibb.26 Sept 2024 — FDA approval — FDA approves COBENFY (xanomeline and trospium chloride) for schizophrenia in adults
Phase change Readout Event UpcomingHover a marker for details.
Phase 3Dec 2020 – Jun 2027
  1. UpcomingTopline from ADEPT-4, the second acute-efficacy Phase 3 of Cobenfy in Alzheimer's disease psychosis (NPI-C H+D primary endpoint): among readouts beginning early 2027 and spread across the year.Alzheimer's disease psychosis↗
  2. UpcomingTopline from ADEPT-1, the Phase 3 relapse-prevention (randomized-withdrawal) study of Cobenfy in Alzheimer's disease psychosis: among readouts beginning early 2027 and spread across the year, with a potential interim analysis later in 2026.Alzheimer's disease psychosis↗
  3. UpcomingTopline results from ADEPT-2, the first acute-efficacy Phase 3 of Cobenfy in Alzheimer's disease psychosis (primary endpoint: change in NPI-C Hallucinations and Delusions score), now expected among readouts beginning early 2027.Alzheimer's disease psychosis↗
  4. ADEPT-2 continuation announcement: BMS identified 'irregularities due to clinical trial execution at a small number of study sites', excluded those sites' patient data from the primary analysis, had an independent party assess the collected data, and per the Data Monitoring Committee's recommendation continued the trial with additional enrollment (BMS remaining blinded). ADEPT-1/-2/-4 readouts guided to end-2026 at that time; on 2026-07-30 (Q2 2026 earnings) guidance moved again to topline readouts beginning early 2027, spread across the year. Phase and status unchanged — recorded because the enrollment extension and readout slips are material program events with no fitting event_type code.Alzheimer's disease psychosis↗
  5. metEMERGENT-3 (Phase 3) topline positive: KarXT met the primary endpoint with an 8.4-point reduction in PANSS total score vs placebo at week 5, the third consecutive positive registrational trial.Schizophrenia↗
  6. ADEPT-1 (NCT05511363, CN012-0026) started per ClinicalTrials.gov: the ADP program opened directly in Phase 3 with a randomized-withdrawal relapse-prevention design (open-label KarXT, then randomization to continue or withdraw; primary endpoint time from randomization to relapse over 38 weeks). Started under Karuna Therapeutics, pre-acquisition.Alzheimer's disease psychosis
  7. metEMERGENT-2 (Phase 3) topline positive: KarXT met the primary endpoint with a statistically significant 9.6-point reduction in PANSS total score vs placebo at week 5 (p<0.0001), and met key secondary endpoints on PANSS positive, negative and Marder negative-factor subscales.Schizophrenia↗
  8. Licensing dealKaruna licenses KarXT Greater China rights to Zai Lab ($35M upfront)↗
  9. metEMERGENT-1 (Phase 2) published in NEJM: xanomeline-trospium reduced PANSS total score by 11.6 points more than placebo at week 5 (p<0.001) in 182 hospitalized adults with acute schizophrenia, without D2-antagonist-typical adverse events.Schizophrenia↗
  10. EMERGENT-2 (NCT04659161, KAR-007) started: first Phase 3, 252 acutely psychotic hospitalized adults, PANSS total at week 5. Topline positive 2022-08-08 (-9.6 points vs placebo, p<0.0001); published in The Lancet 2024-01-13. EMERGENT-3 (NCT04738123) followed in April 2021 and read out positive 2023-03-20 (-8.4 points).Schizophrenia
ApprovedSept 2024 – Dec 2025
  1. NMPA approval (China)China's NMPA approves COBENFY for schizophrenia in adults (via Zai Lab)Schizophrenia↗
  2. missedARISE (Phase 3, adjunctive to atypical antipsychotics) MISSED its primary endpoint: Cobenfy added to an atypical antipsychotic reduced PANSS total score by 2.0 points vs placebo+antipsychotic at week 6, not statistically significant (p=0.11).Schizophrenia↗
  3. FDA approved COBENFY (xanomeline and trospium chloride) capsules, NDA 216158, for the treatment of schizophrenia in adults, on the PDUFA date. First-in-class muscarinic antipsychotic; openFDA records the original approval as a TYPE 1 (new molecular entity) submission by Bristol-Myers Squibb.Schizophrenia↗
  4. FDA approvalFDA approves COBENFY (xanomeline and trospium chloride) for schizophrenia in adultsSchizophrenia↗
Filed (NDA)Sept 2023 – Mar 2024
  1. AcquisitionBristol Myers Squibb completes its $14.0 billion acquisition of Karuna Therapeutics↗
  2. PDUFA date setFDA accepts the KarXT NDA and sets a PDUFA date of September 26, 2024Schizophrenia↗
  3. Karuna submitted the NDA for KarXT for schizophrenia in adults in September 2023 (exact day not disclosed in the acceptance release; dated month-end as an upper bound). FDA accepted the NDA on 2023-11-29 and set a PDUFA action date of 2024-09-26. Supported by EMERGENT-1/-2/-3 (efficacy) and EMERGENT-4/-5 (long-term safety).Schizophrenia↗
  4. NDA/BLA filedKaruna submits the KarXT NDA for schizophrenia to the FDASchizophrenia↗
Phase 2Sept 2018
  1. EMERGENT-1 (NCT03697252, KAR-004) started: Phase 2, randomized, double-blind, placebo-controlled, 182 hospitalized adults with acute schizophrenia; primary endpoint change in PANSS total at week 5. Positive: -11.6 points vs placebo (published NEJM 2021-02-25). Xanomeline itself had earlier Lilly-era clinical history in the 1990s; this history starts with the KarXT combination.Schizophrenia

Xanomeline/trospium chloride (Cobenfy) for Schizophrenia#

ApprovedApprovedSchizophrenia indication →

Xanomeline/trospium chloride (KarXT) for schizophrenia — the lead and approved indication. FDA-approved as COBENFY on 2024-09-26 (NDA 216158) for schizophrenia in adults: the first antipsychotic acting through muscarinic receptors rather than dopamine D2 blockade, and the first new mechanism of action for schizophrenia in decades. Approval rested on the EMERGENT program: EMERGENT-1 (Phase 2, PANSS -11.6 vs placebo), EMERGENT-2 and EMERGENT-3 (Phase 3, PANSS -9.6 and -8.4 at week 5, both p<0.0001) plus the EMERGENT-4/-5 long-term safety studies. Approved in China 2025-12-23 via licensee Zai Lab; a UK MHRA application via the International Recognition Procedure is planned with a 2026 launch. Within-schizophrenia lifecycle: the ADJUNCTIVE thrust (Cobenfy added to atypical antipsychotics in inadequately controlled patients) MISSED its primary endpoint in the Phase 3 ARISE trial on 2025-04-22 (PANSS -2.0 vs placebo, p=0.11; BMS said preliminary analyses suggested benefit in patients on non-risperidone backgrounds and that it would discuss the data with the FDA — no adjunctive filing has followed). Ongoing: EMERGENT TEEN (adolescents 13-17, Phase 3), a relapse-prevention randomized-withdrawal Phase 3, Japan and China registration studies, a Phase 1 long-acting injectable, and Phase 4 urological-safety and lactation studies. Cobenfy revenue was $63M in Q2 2026 (+81% y/y).

Readouts

  • 2025-04-22ReportedTopline datamissedNCT05145413

    ARISE (Phase 3, adjunctive to atypical antipsychotics) MISSED its primary endpoint: Cobenfy added to an atypical antipsychotic reduced PANSS total score by 2.0 points vs placebo+antipsychotic at week 6, not statistically significant (p=0.11). ↗

  • 2023-03-20ReportedTopline datametNCT04738123

    EMERGENT-3 (Phase 3) topline positive: KarXT met the primary endpoint with an 8.4-point reduction in PANSS total score vs placebo at week 5, the third consecutive positive registrational trial. ↗

  • 2022-08-08ReportedTopline datametNCT04659161

    EMERGENT-2 (Phase 3) topline positive: KarXT met the primary endpoint with a statistically significant 9.6-point reduction in PANSS total score vs placebo at week 5 (p<0.0001), and met key secondary endpoints on PANSS positive, negative and Marder negative-factor subscales. ↗

  • 2021-02-25ReportedFull resultsmetNCT03697252

    EMERGENT-1 (Phase 2) published in NEJM: xanomeline-trospium reduced PANSS total score by 11.6 points more than placebo at week 5 (p<0.001) in 182 hospitalized adults with acute schizophrenia, without D2-antagonist-typical adverse events. ↗

Xanomeline/trospium chloride (Cobenfy) for Alzheimer's disease psychosis#

Phase 3RecruitingAlzheimer's disease psychosis indication →

Xanomeline/trospium chloride (Cobenfy/KarXT) for psychosis associated with Alzheimer's disease (ADP) — the ADEPT Phase 3 program, the franchise's largest post-approval bet. There is no FDA-approved treatment for ADP, and off-label D2 antipsychotics carry a boxed warning for increased mortality in elderly dementia patients. Five trials: ADEPT-1 (NCT05511363, randomized-withdrawal relapse prevention, primary endpoint time to relapse over 38 weeks, started 2022-08-23), ADEPT-2 (NCT06126224, acute efficacy, primary endpoint change in NPI-C Hallucinations+Delusions score, started 2023-08-28), ADEPT-3 (NCT05980949, open-label long-term safety extension), ADEPT-4 (NCT06585787, second acute efficacy study, started 2024-09-26), and ADEPT-5 (NCT06947941, KarXT + KarX-EC, started 2026-03-25). The program has slipped twice. On 2025-12-03 BMS disclosed 'irregularities due to clinical trial execution at a small number of study sites' in ADEPT-2: it excluded those sites' data from the primary analysis, brought in an independent assessor, and — on the Data Monitoring Committee's recommendation, remaining blinded — continued the study with additional enrollment, guiding ADEPT-1/-2/-4 readouts to end-2026. On the Q2 2026 earnings (2026-07-30) BMS pushed again, citing enrollment pace in ADEPT-2/-4 and slower-than-projected relapse accrual in ADEPT-1: topline readouts are now anticipated to begin in early 2027 and be spread across the year, with a potential ADEPT-1 interim analysis later in 2026. No efficacy data from any ADEPT trial has been reported; all five trials are recruiting as of 2026-08-12.

Readouts

  • 2027DelayedTopline dataNCT06585787

    Topline from ADEPT-4, the second acute-efficacy Phase 3 of Cobenfy in Alzheimer's disease psychosis (NPI-C H+D primary endpoint): among readouts beginning early 2027 and spread across the year. ↗

  • 2027 (potential interim analysis late 2026)DelayedTopline dataNCT05511363

    Topline from ADEPT-1, the Phase 3 relapse-prevention (randomized-withdrawal) study of Cobenfy in Alzheimer's disease psychosis: among readouts beginning early 2027 and spread across the year, with a potential interim analysis later in 2026. ↗

  • early 2027DelayedTopline dataNCT06126224

    Topline results from ADEPT-2, the first acute-efficacy Phase 3 of Cobenfy in Alzheimer's disease psychosis (primary endpoint: change in NPI-C Hallucinations and Delusions score), now expected among readouts beginning early 2027. ↗

Clinical trials#

NCT07686263CN012-0006Phase 3Activen=472

A Phase 3 Double-blind, Placebo-controlled Randomized Withdrawal Maintenance (Relapse Prevention) Trial of KarXT in Participants With Schizophrenia

Started Sept 2026· Primary completion Mar 2029

NCT06947941CN012-0034Phase 3Recruitingn=325

ADEPT-5: A Phase 3, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of KarXT + KarX-EC for Psychosis Associated With Alzheimer's Disease

Started Mar 2026· Primary completion Feb 2028· 22 sites across 5 countries

United KingdomUnited StatesCanadaJapan

NCT07288567CN012-0020Phase 3Recruitingn=166

EMERGENT TEEN: A Phase 3, Randomized, Double-blind, Placebo-controlled Study of KarXT for Schizophrenia in Adolescents (13 to 17 Years of Age)

Started Jan 2026· Primary completion Dec 2029· 41 sites across 5 countries

United StatesRomaniaJapanArgentina

NCT07061288CN012-0016Phase 1Recruitingn=116

An Open-label, Phase 1, Dose-Finding Study of a Long-Acting Injectable KarXT Formulation in Participants With Schizophrenia

Started Sept 2025· Primary completion Jun 2027· 8 sites across 1 country

United States

NCT06882785CN012-0019Phase 3Recruitingn=250

A Phase 3, Randomized, Two-part Study (5-week Double-blind, Placebo-controlled + 52-week Open-label Extension) of KarXT in Acutely Psychotic Japanese Adults With Schizophrenia

Started Jun 2025· Primary completion Sept 2028· 56 sites across 1 country

Japan

Show all 19 trials

NCT06572449CN012-0048Phase 3Completedn=173

A Phase 3 Study to Assess Safety and Effectiveness of a Slower Titration and Food Effect of KarXT in Adults With Schizophrenia

Started Oct 2024· Primary completion Mar 2025· 6 sites across 1 country

United States

NCT06585787CN012-0056Phase 3Recruitingn=406

ADEPT-4: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Safety and Efficacy of KarXT for Psychosis Associated With Alzheimer's Disease

Started Sept 2024· Primary completion Nov 2026· 289 sites across 25 countries

United StatesJapanChinaSouth Korea

NCT06126224CN012-0027Phase 3Recruitingn=500

ADEPT-2: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Safety and Efficacy of KarXT for Psychosis Associated With Alzheimer's Disease

Started Aug 2023· Primary completion Dec 2026· 154 sites across 14 countries

United StatesChinaUnited KingdomPoland

NCT05980949CN012-0028Phase 3Recruitingn=1000

ADEPT-3: Open-Label Extension Study of the Long-Term Safety and Tolerability of KarXT in Subjects With Psychosis Associated With Alzheimer's Disease

Started Jul 2023· Primary completion Sept 2027· 428 sites across 31 countries

United StatesChinaJapanItaly

NCT05919823CN012-0063Phase 3Completedn=202

A Phase 3 Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adults With DSM-5 Schizophrenia (double-blind part + 12-week open-label extension)

Started May 2023· Primary completion Sept 2024· 28 sites across 1 country

China

NCT05643170KAR-014Phase 3Discontinuedn=4

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

Started Nov 2022· Primary completion Mar 2023· 5 sites across 1 country

United States

NCT05511363CN012-0026Phase 3Recruitingn=410

ADEPT-1: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Relapse Prevention Study of KarXT for Psychosis Associated With Alzheimer's Disease

Started Aug 2022· Primary completion Oct 2026· 116 sites across 11 countries

United StatesSerbiaItalySpain

NCT05304767CN012-0009Phase 3Completedn=290

An Open-label Extension Study to Assess the Long-term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Started Mar 2022· Primary completion Mar 2026· 175 sites across 9 countries

United StatesBulgariaIndiaSerbia

NCT05145413CN012-0008Phase 3Completedn=396

ARISE: A Phase 3 Study to Evaluate the Safety and Efficacy of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Started Nov 2021· Primary completion Mar 2025· 166 sites across 8 countries

United StatesBulgariaIndiaSerbia

NCT04820309CN012-0007Phase 3Completedn=566

EMERGENT-5: An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in De Novo Subjects With DSM-5 Schizophrenia

Started Jun 2021· Primary completion May 2024· 117 sites across 2 countries

United StatesPuerto Rico

NCT04738123KAR-009Phase 3Completedn=256

EMERGENT-3: A Phase 3 Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia

Started Apr 2021· Primary completion Nov 2022· 32 sites across 2 countries

United StatesUkraine

NCT04659174KAR-008Phase 3Completedn=152

EMERGENT-4: An Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Subjects With DSM-5 Schizophrenia

Started Feb 2021· Primary completion Oct 2023· 44 sites across 2 countries

United StatesUkraine

NCT04659161KAR-007Phase 3Completedn=252

EMERGENT-2: A Phase 3 Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia

Started Dec 2020· Primary completion May 2022· 22 sites across 1 country

United States

NCT03697252KAR-004Phase 2Completedn=182

EMERGENT-1: A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia

Started Sept 2018· Primary completion Sept 2019· 12 sites across 1 country

United States

Conference coverage#

KarXT appears in 11 CNS Pulse conference abstracts:

+ 3 more.

Sources#

  1. Brannan SK, et al. Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia (EMERGENT-1). N Engl J Med. 2021;384(8):717-726 — New England Journal of Medicine / PubMed
  2. Bristol Myers Squibb Announces Continuation of ADEPT-2 Phase 3 Study in Psychosis Associated with Alzheimer's Disease (2025-12-03; site-conduct irregularities, data exclusion, additional enrollment, readouts guided to end-2026) — Bristol Myers Squibb
  3. Bristol Myers Squibb Announces Topline Results from Phase 3 ARISE Trial of Cobenfy as an Adjunctive Treatment to Atypical Antipsychotics in Adults with Schizophrenia (2025-04-22; primary endpoint not met, PANSS -2.0, p=0.11) — Bristol Myers Squibb
  4. Bristol Myers Squibb Completes Acquisition of Karuna Therapeutics, Strengthening Neuroscience Portfolio (2024-03-18; $330/share, $14.0B) — Bristol Myers Squibb
  5. Bristol Myers Squibb Reports Second Quarter Financial Results for 2026 (2026-07-30; Cobenfy revenue $63M, +81%) — Bristol Myers Squibb
  6. COBENFY (xanomeline and trospium chloride) capsules — FDA prescribing information (SPL, E.R. Squibb & Sons; mechanism 12.1, PK 12.3, dosage 2.2) — DailyMed (U.S. National Library of Medicine)
  7. Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-2 Trial of KarXT in Schizophrenia (2022-08-08; PANSS -9.6 vs placebo, p<0.0001) — Karuna Therapeutics
  8. Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-3 Trial of KarXT in Schizophrenia (2023-03-20; PANSS -8.4 vs placebo) — Karuna Therapeutics
  9. Karuna Therapeutics Announces U.S. FDA Accepts New Drug Application for KarXT for the Treatment of Schizophrenia (2023-11-29; PDUFA 2024-09-26; NDA submitted September 2023) — Karuna Therapeutics (via BioSpace)
  10. NCT03697252 (KAR-004) — EMERGENT-1, Phase 2, KarXT in hospitalized adults with schizophrenia — ClinicalTrials.gov (U.S. National Library of Medicine)
Show all 31 sources
  1. NCT04659161 (KAR-007) — EMERGENT-2, Phase 3, KarXT in acutely psychotic hospitalized adults — ClinicalTrials.gov (U.S. National Library of Medicine)
  2. NCT04659174 (KAR-008) — EMERGENT-4, open-label long-term safety extension — ClinicalTrials.gov (U.S. National Library of Medicine)
  3. NCT04738123 (KAR-009) — EMERGENT-3, Phase 3, KarXT in acutely psychotic hospitalized adults — ClinicalTrials.gov (U.S. National Library of Medicine)
  4. NCT04820309 (CN012-0007) — EMERGENT-5, open-label long-term safety in de novo subjects — ClinicalTrials.gov (U.S. National Library of Medicine)
  5. NCT05145413 (CN012-0008) — ARISE, Phase 3 adjunctive KarXT in inadequately controlled schizophrenia — ClinicalTrials.gov (U.S. National Library of Medicine)
  6. NCT05304767 (CN012-0009) — ARISE open-label extension (adjunctive KarXT long-term safety) — ClinicalTrials.gov (U.S. National Library of Medicine)
  7. NCT05511363 (CN012-0026) — ADEPT-1, Phase 3 randomized-withdrawal relapse-prevention study of KarXT in ADP (primary endpoint: time to relapse over 38 weeks) — ClinicalTrials.gov (U.S. National Library of Medicine)
  8. NCT05643170 (KAR-014) — open-label durability study, TERMINATED after 4 participants ('Company's business decision') — ClinicalTrials.gov (U.S. National Library of Medicine)
  9. NCT05919823 (CN012-0063) — Phase 3 KarXT in acutely psychotic hospitalized Chinese adults (supported the NMPA approval) — ClinicalTrials.gov (U.S. National Library of Medicine)
  10. NCT05980949 (CN012-0028) — ADEPT-3, open-label long-term safety and tolerability extension of KarXT in ADP — ClinicalTrials.gov (U.S. National Library of Medicine)
  11. NCT06126224 (CN012-0027) — ADEPT-2, Phase 3 acute-efficacy study of KarXT in ADP (primary endpoint: change in NPI-C Hallucinations and Delusions score) — ClinicalTrials.gov (U.S. National Library of Medicine)
  12. NCT06572449 (CN012-0048) — Phase 3 slower-titration and food-effect study of KarXT — ClinicalTrials.gov (U.S. National Library of Medicine)
  13. NCT06585787 (CN012-0056) — ADEPT-4, Phase 3 acute-efficacy study of KarXT in ADP (registered under condition 'Alzheimer Disease'; ADP asserted by the official title) — ClinicalTrials.gov (U.S. National Library of Medicine)
  14. NCT06882785 (CN012-0019) — Phase 3 KarXT in acutely psychotic Japanese adults (5-week DB + 52-week OLE) — ClinicalTrials.gov (U.S. National Library of Medicine)
  15. NCT06947941 (CN012-0034) — ADEPT-5, Phase 3 study of KarXT + KarX-EC in ADP (started 2026-03-25) — ClinicalTrials.gov (U.S. National Library of Medicine)
  16. NCT07061288 (CN012-0016) — Phase 1 dose-finding study of a long-acting injectable KarXT formulation — ClinicalTrials.gov (U.S. National Library of Medicine)
  17. NCT07288567 (CN012-0020) — EMERGENT TEEN, Phase 3 KarXT in adolescents 13-17 with schizophrenia — ClinicalTrials.gov (U.S. National Library of Medicine)
  18. NCT07686263 (CN012-0006) — Phase 3 randomized-withdrawal relapse-prevention trial of KarXT — ClinicalTrials.gov (U.S. National Library of Medicine)
  19. U.S. FDA Approves Bristol Myers Squibb's COBENFY (xanomeline and trospium chloride), a First-In-Class Muscarinic Agonist for the Treatment of Schizophrenia in Adults (2024-09-26) — Bristol Myers Squibb
  20. Zai Lab and Karuna Therapeutics Announce Strategic Collaboration for Development, Manufacturing, and Commercialization of KarXT in Greater China (2021-11-09; $35M upfront) — Zai Lab / Karuna Therapeutics (via GlobeNewswire)
  21. Zai Lab Announces Approval of COBENFY (xanomeline and trospium chloride) in China, a First-in-Class Therapy for Schizophrenia (NMPA approval 2025-12-23) — Zai Lab Limited