A Phase 1 Open-label Trial to Evaluate the Pharmacokinetics and Safety Following a Single Dose of Emraclidine in Adult Participants With Mild, Moderate, and Severe Renal Impairment Compared With Adult Participants With Normal Renal Function
Overview
- Phase
- Phase 1
- Intervention
- Emraclidine
- Conditions
- Renal Impairment
- Sponsor
- AbbVie
- Enrollment
- 58
- Locations
- 4
- Primary Endpoint
- Maximum Observed Plasma Concentration (Cmax) of Emraclidine
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The primary purpose of this study is to assess the effect of renal impairment on the pharmacokinetics (PK) of emraclidine following administration of a single oral dose in participants with mild, moderate, and severe renal impairment relative to matched participants with normal renal function.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For All Participants
- •Body mass index of ≥18.0 to 42.0 kilograms per meter square (kg/m\^2), inclusive, and a total body weight ≥50 kilograms (kg) (110 pounds \[lbs\]).
- •Sexually active women of childbearing potential must agree to use at least an acceptable birth control method during the trial and for 7 days after the last dose of investigational medicinal product (IMP).
- •Additional Criteria for Participants With Normal Renal Function
- •Age that is within ±10 years of the median age for the renal impairment groups.
- •Body weight that is within ±15% of the median body weight for the renal impairment groups.
- •Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
- •Normal renal function: Estimated glomerular filtration rate (eGFR) ≥90 milliliter per minute (mL/min) determined using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function assessed at Baseline (Check-in/Day -1) should not deviate more than 30% from the Screening value.
- •Additional Criteria for Participants With Renal Impairment
- •Mild, moderate, or severe renal impairment based on eGFR determined using the 2021 CKD-EPI equation. Renal function assessed at Baseline (Check-in/Day -1) should not deviate more than 30% from the Screening value.
Exclusion Criteria
- •For All Participants
- •"Yes" responses for any of the following items on the C-SSRS (within the individual's lifetime):
- •Suicidal Ideation Item 3 (Active Suicidal Ideation with Any Methods \[Not Plan\] without Intent to Act)
- •Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan)
- •Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent)
- •Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior) "Yes" responses for any of the following items on the C-SSRS (within past 12 months):
- •Suicidal Ideation Item 1 (Wish to be Dead)
- •Suicidal Ideation Item 2 (Non-Specific Active Suicidal Thoughts) Any "yes" response on Suicidal Ideation Item 1 or Item 2 that was within the individual's lifetime but not within the past 12 months should be discussed with the medical monitor prior to inclusion of the participant in the trial.
- •Serious risk of suicide in the opinion of the investigator is also exclusionary.
- •History of moderate to severe substance or alcohol-use disorder (excluding nicotine or caffeine) as per DSM-5 criteria within 12 months prior to signing the informed consent form (ICF).
Arms & Interventions
Mild Renal Impairment
Participants will receive a single oral dose of 10 milligrams (mg) emraclidine on Day 1.
Intervention: Emraclidine
Moderate Renal Impairment
Participants will receive a single oral dose of 10 mg emraclidine on Day 1.
Intervention: Emraclidine
Severe Renal Impairment
Participants will receive a single oral dose of 10 mg emraclidine on Day 1.
Intervention: Emraclidine
Normal Renal Function
Participants will receive a single oral dose of 10 mg emraclidine on Day 1.
Intervention: Emraclidine
Outcomes
Primary Outcomes
Maximum Observed Plasma Concentration (Cmax) of Emraclidine
Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 5
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Emraclidine
Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 5
Area Under the Plasma Concentration-time Curve from Time Zero to t (AUC0-t) of Emraclidine
Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 5
Area Under the Unbound Plasma Concentration-time Curve from Time Zero to t (AUC0-t,u) of Emraclidine
Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 5
Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Emraclidine
Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 5
Area Under the Unbound Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf,u) of Emraclidine
Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 5
Secondary Outcomes
- Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)(Up to Day 15)
- Number of Participants With Clinically Significant Changes in Vital Signs(Up to Day 5)
- Number of Participants With Clinically Significant Change in Laboratory Assessments(Up to Day 5)
- Number of Participants With Clinically Significant Change in Physical and Neurological Examination Results(Up to Day 5)
- Changes in Columbia Suicide Severity Rating Scale (C-SSRS) Score(Up to Day 5)
- Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values(Up to Day 5)