Clinical trial NCT05940402: A Study to Evaluate Pharmacokinetic and Safety Trial of Emraclidine in Participants With Renal Impairment Compared With Participants With Normal Renal Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2023-07-11
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

1. 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).
2. 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.
3. 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.
   * Stable disease, defined as no clinically significant changes in disease status as documented by most recent eGFR assessment (within at least 3 months before Screening).
   * Stable concomitant medications for the management of individual participant's medical history; on a case-by-case basis, with input from the sponsor, participants receiving fluctuating concomitant medication/treatment may be considered if the underlying disease is under control.

Key Exclusion Criteria:

1. 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).
   * Receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or booster within 7 days of planned dosing.

   In addition, participants who plan to receive SARS-CoV-2 vaccination or booster while participating in the trial or for a minimum of 7 days (to cover at least 5 half-lives of IMP) after the last dose of investigational medicinal product (IMP) will be excluded.

   - Have recently been diagnosed with symptomatic coronavirus disease-2019 (COVID-19) or test positive (i.e., using polymerase chain reaction \[PCR\] or rapid antigen test) for SARS-CoV-2 within 15 days prior to signing the ICF.
2. Additional Criteria for Participants With Normal Renal Function

   - Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for surgically excised non-melanomatous skin cancers or in situ cervical cancer, at the discretion of the investigator), hematological, immunological, neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
3. Additional Criteria for Participants With Renal Impairment

   * Evidence of disease that is not explained by current/known medical history, i.e., organ dysfunction (including malignancies) or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with renal impairment and other underlying conditions.
   * Participants who have received an organ transplant or are currently waiting for an organ transplant and are listed on the national transplant list.
   * Participants who require dialysis
   * Participants with nephrotic syndrome.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Emraclidine
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 5
measure: Maximum Observed Unbound Plasma Concentration (Cmax,u) of Emraclidine
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 5
measure: Area Under the Plasma Concentration-time Curve from Time Zero to t (AUC0-t) of Emraclidine
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 5
measure: Area Under the Unbound Plasma Concentration-time Curve from Time Zero to t (AUC0-t,u) of Emraclidine
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 5
measure: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Emraclidine
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 5
measure: Area Under the Unbound Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf,u) of Emraclidine
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 5
Secondary outcomes:
measure: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 15
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values
timeFrame: Up to Day 5
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Up to Day 5
measure: Number of Participants With Clinically Significant Change in Laboratory Assessments
timeFrame: Up to Day 5
measure: Number of Participants With Clinically Significant Change in Physical and Neurological Examination Results
timeFrame: Up to Day 5
measure: Changes in Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Up to Day 5
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Tustin, California
state: California
city: Miami
country: United States
facility: Miami, Florida
state: Florida
city: Miami
country: United States
facility: Miami, Florida
state: Florida
city: Orlando
country: United States
facility: Orlando, Florida
state: Florida
city: Knoxville
country: United States
facility: Knoxville, Tennessee
state: Tennessee
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: