Schizophrenia
Conditions
Keywords
Schizophrenia, ABBV-1231
Brief summary
Schizophrenia is a common and severe psychiatric illness characterized by extreme disturbances of cognition and thought, affecting language, perception and sense of self. This study will assess adverse events, change in disease activity, and how oral emraclidine moves through the body in adult participants with schizophrenia Emraclidine is an investigational drug being developed for the treatment of schizophrenia. Participants are placed in one of two parts, Part A or Part B, where each group will receive a different treatment. Participants will receive either oral emraclidine or placebo. Approximately 268 participants will be enrolled across roughly 32 sites in the United States. Participants in Part A will be assigned to oral emraclidine or placebo administered for 14 days or up to 21 days depending on cohort. Cohorts without titration include a 14-day treatment period at target dose. Cohorts with titration are comprised of a titration period of up to 7 days and a 14-day treatment period at the cohort target dose. Participants in Part B will receive oral emraclidine or placebo. Participants will be followed for 30 days after the last dose of the study drug. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGEmraclidine
Oral Tablets
DRUGPlacebo
Oral Tablets
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* BMI within 18 to 40 kg/m2 (inclusive of both values), and body weight \> 50 kg (110 lbs). * (Part A only): Positive and Negative Syndrome Scale (PANSS) total score \< 80 at Screening and at Baseline * (Part B only): Participant experiencing an acute exacerbation of psychotic symptoms with onset less than 2 months prior to Screening * (Part B only): Participant must have a PANSS total score from 80 to 120, inclusive, at Screening and at Baseline * (Part B only): Participant MUST have a score of ≥ 4 (moderate or greater) for ≥ 2 of the following PANSS Positive Scale items at Screening and at Baseline * (Part B only): Participant must have a Clinical Global Impression of Severity (CGIS) score ≥ 4 (at least moderately ill) at Screening and Baseline
Exclusion criteria
* Any primary DSM-5 disorder other than schizophrenia (current nicotine use disorder and caffeine use disorder are allowed) within 12 months before Screening. * History of clozapine exposure. * History of treatment resistance to schizophrenia medications, defined as failure to respond to 2 or more adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the last 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) | Up to approximately 74 days | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. |
| Part A Only-Maximum Observed Plasma Concentration (Cmax) of Emraclidine | Up to approximately 24 days | Cmax of Emraclidine |
| Part A Only-Time to Cmax (Tmax) of Emraclidine | Up to approximately 24 days | Tmax of Emraclidine |
| Part A Only-Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) of Emraclidine | Up to approximately 24 days | AUCt of Emraclidine |
| Part A Only-Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Emraclidine | Up to approximately 24 days | AUCtau of Emraclidine |
| Part A Only- Minimum plasma concentration (Cmin) of Emraclidine | Up to approximately 21 days | Cmin of Emraclidine |
| Part A Only-Average plasma concentration (Cavg) of Emraclidine | Up to approximately 21 days | Cavg of Emraclidine |
| Part A Only- Terminal Phase Elimination Half-Life (t1/2) of Emraclidine | Up to approximately 21 days | Terminal phase elimination half-life of Emraclidine |
| Part A Only-Terminal elimination rate constant (λz) of Emraclidine | Up to approximately 21 days | λz of Emraclidine |
| Part A Only-Apparent Clearance of Drug from Plasma (CL/F) of Emraclidine | Up to approximately 21 days | CL/F of Emraclidine |
| Part A Only-Apparent Volume of Distribution DuringTerminal Phase (Vz/F) of Emraclidine | Up to approximately 21 days | Vz/F of Emraclidine |
| Part A Only-Peak-to-trough ratio (PTR) of Emraclidine | Up to approximately 21 days | PTR of Emraclidine |
| Part A Only- Accumulation ratio for Cmax (RacCmax) of Emraclidine | Up to approximately 21 days | RacCmax of Emraclidine |
| Part A Only-Accumulation ratio for AUCtau (RacAUCtau) of Emraclidine | Up to approximately 21 days | RacAUCtau of Emraclidine |
| Part A Only-Maximum Observed Plasma Concentration (Cmax) of Metabolite (CV-0000364) | Up to approximately 24 days | Cmax of Metabolite (CV-0000364) |
| Part A Only-Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Metabolite (CV-000036) | Up to approximately 24 days | AUCtau of Metabolite (CV-000036) |
| Part A Only-Time to Cmax (Tmax) of Metabolite (CV-0000364) | Up to approximately 24 days | Tmax of Metabolite (CV-0000364) |
| Part A Only-Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) Metabolite (CV-000036) | Up to approximately 24 days | AUCt of Metabolite (CV-000036) |
| Part A Only-Metabolite to Parent Ratio (MRCmax) of Metabolite (CV-0000364) calculated from Cmax | Up to approximately 21 days | MRCmax of Metabolite (CV-000036) |
| Part A Only- Metabolite to Parent Ratio (MRAUCtau) of Metabolite (CV-0000364) | Up to approximately 21 days | MRAUCtau of Metabolite (CV-0000364) |
| Part A Only- Terminal Phase Elimination Half-Life (t1/2) of of Metabolite (CV-0000364) | Up to approximately 21 days | Terminal phase elimination half-life of Metabolite (CV-0000364) |
| Part A Only-Terminal elimination rate constant (λz) of Metabolite (CV-0000364) | Up to approximately 21 days | λz of Metabolite (CV-0000364) |
| Part A Only-Peak-to-trough ratio (PTR) of Metabolite (CV-0000364) | Up to approximately 21 days | PTR of Metabolite (CV-0000364) |
| Part B Only-Change from Baseline in Positive and Negative Syndrome Scale (PANSS) total score | Up to approximately week 6 | PANSS is a 30-item clinician-reported rating scale which assesses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS consists of 3 subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. |
| Part B Only-Maximum Observed Plasma Concentration (Cmax) of Emraclidine | Up to approximately 24 days | Cmax of Emraclidine |
| Part B Only-Time to Cmax (Tmax) of Emraclidine | Up to approximately 24 days | Tmax of Emraclidine |
| Part B Only-Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) of Emraclidine | Up to approximately 24 days | AUCt of Emraclidine |
| Part B Only-Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Emraclidine | Up to approximately 24 days | AUCtau of Emraclidine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B Only-Change from Baseline in in Clinical Global Impression of Severity (CGIS) score | Up to approximately Week 6 | CGIS is a single, clinician-reported item that measures the clinician's impression of a participant's current anxiety severity considering their total clinical experience with the patient population. The measure uses a 7-point Likert rating scale with responses ranging from "normal, to at all ill" (1) to "among the most extremely ill patients" (5), with higher scores indicating greater anxiety severity. |
| Part B Only-Change from Baseline in Positive and Negative Syndrome Scale (PANSS) total score | Up to approximately 74 days | PANSS is a 30-item clinician-reported rating scale which assesses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS consists of 3 subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. |
| Part B Only-Number of Participants achieving ≥ 30% improvement in PANSS total score | Up to approximately week 6 | PANSS is a 30-item clinician-reported rating scale which assesses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS consists of 3 subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. |
| Part B Only-Number of Participants achieving remission (PANSS total score ≤ 60) | Up to approximately week 6 | PANSS is a 30-item clinician-reported rating scale which assesses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS consists of 3 subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. |
Countries
United States
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed