Clinical trial NCT06729970: A Study to Evaluate the Effects of Lithium and Valproic Acid on the Pharmacokinetics of KarXT and Effects of KarXT on the Pharmacokinetics of Lithium and Valproic Acid in Healthy Participants
Official title: A Phase 1, 4-part, Open-label, Fixed-sequence Study to Evaluate the Effects of Lithium and Valproic Acid on the Single-dose Pharmacokinetics of KarXT and Effects of KarXT on the Single-dose Pharmacokinetics of Lithium and Valproic Acid in Healthy Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: KarXT
Lithium
Valproic acid
Drug-Drug Interaction study
Healthy Volunteers
BMS-986510
Pharmacokinetics
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-12-12
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel A \& B cohorts and then Parallel C \& D cohorts.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effects of lithium and valproic acid on the single-dose pharmacokinetics (PK) of KarXT and the effect of KarXT on the single-dose PK of lithium and valproic acid in healthy participants.


Eligibility criteria: Inclusion Criteria:

* Healthy male and female \[individual not of childbearing potential (INOCBP)\] participants as determined by no clinically significant deviation from normal in medical history, physical examination, 12-lead ECG, vital signs, and clinical laboratory determinations.
* BMI of 18.0 to 32.0 kg/m2, inclusive.

Exclusion Criteria:

* History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, GI, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results. Note: Any grade of hepatic impairment (Child-Pugh Grade A or higher) is excluded.
* Parts B and D only: History of pancreatitis.
* Any significant acute or chronic medical illness, in the opinion of the investigator.
* History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma or known history of prostate hypertrophy or nocturia.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 and Day 14-16
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))
timeFrame: Day 1-3 and Day 14-16
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
timeFrame: Day 1-3 and Day 14-16
Secondary outcomes:
measure: Number of participants with Adverse Events (AEs)
timeFrame: Up to 28 days post discontinuation of dosing
measure: Number of participants with Severe AEs (SAEs)
timeFrame: Up to 28 days post discontinuation of dosing
measure: Number of participants with physical examination abnormalities
timeFrame: Up to 2 days post discontinuation of dosing
measure: Number of participants with vital sign abnormalities
timeFrame: Up to 2 days post discontinuation of dosing
measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities
timeFrame: Up to 2 days post discontinuation of dosing
measure: Number of participants with clinical laboratory abnormalities
timeFrame: Up to 2 days post discontinuation of dosing
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to 2 days post discontinuation of dosing
measure: Number of participants with AEs of Special Interest (AESIs)
timeFrame: Up to 28 days post discontinuation of dosing
Other outcomes:
Locations:
city: Los Alamitos
country: United States
facility: CenExel Collaborative Neuroscience Research, LLC - Los Alamitos
state: California
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: