Trial Outcomes & Findings for A Trial of the Safety, Tolerability, and Pharmacodynamics of CVL-871 in Subjects With Dementia-Related Apathy (NCT NCT04958031)

A Trial of the Safety, Tolerability, and Pharmacodynamics of CVL-871 in Subjects With Dementia-Related Apathy

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 drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Assessment of clinically significant changes in QT intervals measured by 12-lead ECG recording after the participant has been supine and at rest for at least 5 minutes

Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes. Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen from baseline, considered clinically significant in the medical and scientific judgment of the investigator.

Vital signs measured include systolic and diastolic blood pressures, heart rate, and body temperature. Duplicate blood pressure and heart rate measurements were obtained sitting/supine (after 5 minutes of rest) followed by a single standing measurement (after 2 minutes of rising from sitting/supine position). The duplicate values (sitting/supine) were individually recorded, and the values were averaged by the sponsor for the time point assessment. Participants' body weights were also measured and recorded.

The number of participants with clinically significant changes in physical and neurological examination results was documented.

The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).Higher total scores indicate more suicidal ideation and/or suicidal behavior.

The NPI-C is a participant/caregiver interview covering 14 neuropsychiatric symptom domains (delusions, hallucinations, agitation/aggression, apathy, depression, euphoria, aberrant motor behavior, irritability, disinhibition, anxiety, sleeping, eating, aberrant vocalizations, and dysphoria). The frequency each behavior item are determined on a 5-point scale ranging from 0 (occasionally) to 4 (very frequently). The severity of each behavior item are determined on a 4-point scale ranging from 0 (mild) to 3 (severe). The total NPI-C apathy domain score is the sum of clinician impression severity scores for apathy and ranges from 0-12. Higher scores indicate more severe apathy.

The NPI is a participant/caregiver interview covering 12 neuropsychiatric symptom domains (delusions, hallucinations, agitation/aggression, apathy, depression, euphoria, aberrant motor behavior, irritability, disinhibition, anxiety, sleeping, and eating). The frequency each behavior item are determined on a 5-point scale ranging from 0 (occasionally) to 4 (very frequently). The severity of each behavior item are determined on a 4-point scale ranging from 0 (mild) to 3 (severe). The NPI apathy domain score is the product of frequency score × severity score reported by the caregiver and ranges from 0-12. Higher scores indicate more severe apathy.

The DAIR is a clinician-rated, 16-item structured interview that assess illness-related changes in motivation, emotional responsiveness, and engagement. Apathy item scores range from 0 (never) to 3 (almost always). For questions 1, 9, 11, 12, 13, and 14, rescaled score = original score, and for questions 2 - 8, 10, 15, and 16, rescaled score = 3 - original score. Items are counted for the total score only if the behavior represents a change toward apathy from pre-illness behavior. Total scores can range from 0 to 36, with higher scores indicating more severe apathy.

The AES-C is a clinician-rated 18-item rating scale measures apathy severity in participants. each rated on a 4-point Likert scale ranging from 0 (not at all true) to 3 (very true), with total scores ranging from 0 to 54. Higher scores indicate greater apathy severity.