Clinical trial NCT06605950: A Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of Xanomeline With Trospium Chloride Versus KarXT in Healthy Adult and Elderly Participants of Japanese Ethnicity and to Assess the Effect of Omeprazole on the PK of Xanomeline With Trospium Chloride in Healthy Adult Participants
Official title: A 2-Part, Phase 1, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of Dual-burst Release of Xanomeline With Immediate-Release Trospium Chloride Versus KarXT in Healthy Adult and Elderly Participants of Japanese Ethnicity (Part 1) and an Open-label Study to Assess the Effect of Omeprazole on the Pharmacokinetics of Dual-burst Release of Xanomeline With Immediate-Release Trospium Chloride in Healthy Adult Participants (Part 2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Japanese
Elderly
Adult
Healthy
Pharmacokinetics
BMS-986510
BMS-986519
KarXT
Omeprazole
Drug interaction
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-09-20
Enrollment: 78
Sex: ALL
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of multiple doses of KarXT + KarX-EC capsules versus KarXT capsules in healthy adult and elderly participants of Japanese ethnicity and to assess the effect of multiple doses of omeprazole on the exposure of xanomeline and trospium administered as KarXT + KarX-EC capsules in healthy adult participants.


Eligibility criteria: Inclusion Criteria

* Inclusion Criteria for Healthy Adult Japanese Participants (Group A):.
* Healthy adult participants must be 19 to 55 years of age, inclusive.

  i) Both participant's biological parents are of ethnic Japanese ancestry. Participants must be first generation Japanese.

ii) Must have a body mass index (BMI) of 18.0 to 32.0 kg/m2 (inclusive), at the time of signing the ICF.

iii) Must have an estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min/1.73m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at the screening visit. One repeat measurement is allowed.

* Inclusion Criteria for Healthy Elderly Japanese Participants (Groups B and C):.
* Healthy elderly participants must be 56 to 90 years of age, inclusive.

  i) Both participant's biological parents are of ethnic Japanese ancestry. Participants must be first generation Japanese.

ii) Must have a BMI ≥ 18.0 and ≤ 35.0 kg/m2 (inclusive), at the time of signing the ICF.

iii) Must have an eGFR of \> 60 mL/min/1.73m2 by the CKD-EPI equation at the screening visit. One repeat measurement is allowed.

* Inclusion Criteria for Healthy Adult Participants (Groups D):.
* Healthy adult participants must be 19 to 55 years of age, inclusive.

  i) Participants with any ethnicity can be included.

ii) Must have a BMI of 18.0 to 32.0 kg/m2 (inclusive), at the time of signing the ICF.

iii) Must have an eGFR of ≥ 90 mL/min/1.73m2 by the CKD-EPI equation at the screening visit. One repeat measurement is allowed.

Exclusion Criteria

- Exclusion Criteria for All Participants (Groups A, B, C, and D):.

i) Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.

ii) History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.

iii) Participant has a history of syncope and/or symptomatic orthostatic hypotension in the year prior to Day 1.

iv) History of cancer that has not been in full remission for \>5 years (except basal cell skin cancer or squamous cell skin cancer with history of curative treatment and no recurrence for \> 1 year prior to the screening visit).

* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Number of participants with Adverse Events (AEs)
timeFrame: Up to 28 days post last dose
measure: Number of participants with Serioues AEs (SAEs)
timeFrame: Up to 28 days post last dose
measure: Number of participants with vital sign abnormalities
timeFrame: Up to 28 days post last dose
measure: Body weight
timeFrame: Up to 28 days post last dose
measure: Number of participants with 12-lead electrocardiogram abnormalities
timeFrame: Up to 28 days post last dose
measure: Number of participants with physical examination abnormalities
timeFrame: Up to 28 days post last dose
measure: Number of participants with clinical laboratory assessment abnormalities
timeFrame: Up to 28 days post last dose
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: On Day 30
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to Day 29
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: Up to Day 29
measure: Area under the concentration-time curve in 1 dosing interval (AUC(TAU))
timeFrame: Up to Day 29
measure: Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24))
timeFrame: Up to Day 29
measure: Apparent total body clearance (CLT/F)
timeFrame: Up to Day 29
measure: Apparent volume of distribution (Vz/F)
timeFrame: Up to Day 29
measure: Terminal elimination half-life (T-HALF)
timeFrame: Up to Day 29
Secondary outcomes:
measure: Cmax
timeFrame: Up to Day 29
measure: Tmax
timeFrame: Up to Day 29
measure: AUC(0-24)
timeFrame: Up to Day 29
measure: AUC(TAU)
timeFrame: Up to Day 29
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))
timeFrame: Up to Day 29
measure: CLT/F
timeFrame: Up to Day 29
measure: Vz/F
timeFrame: Up to Day 29
measure: T-HALF
timeFrame: Up to Day 29
measure: Number of participants with AEs
timeFrame: Up to 28 days post last dose
measure: Number of participants with SAEs
timeFrame: Up to 28 days post last dose
measure: Number of participants with vital sign abnormalities
timeFrame: Up to 28 days post last dose
measure: Body weight
timeFrame: Up to 28 days post last dose
measure: Number of participants with 12-lead electrocardiogram abnormalities
timeFrame: Up to 28 days post last dose
measure: Number of participants with physical examination abnormalities
timeFrame: Up to 28 days post last dose
measure: Number of participants with clinical laboratory assessment abnormalities
timeFrame: Up to 28 days post last dose
measure: C-SSRS
timeFrame: On Day 30
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Cenexel ACT (Anaheim Clinical Trials)
state: California
city: Anaheim
country: United States
facility: Local Institution - 0002
state: California
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: