A Phase 2a, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Descriptive Efficacy of BRII-296 in Adults With Severe Postpartum Depression (PPD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 11
- 主要终点
- PK of Brexanolone: Area Under the Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last)
研究概览
简要总结
The primary purpose of this study is to evaluate the safety and tolerability of BRII-296 administered by 2 intramuscular injections, administered with Depo Medrol as assessed by the incidence of adverse events, changes from baseline in vital signs, pulse oximetry, clinical laboratory evaluations, electrocardiograms (ECGs), Stanford Sleepiness Scale (SSS), Glasgow Coma Scale (GCS) in conjunction with clinical assessment, and suicidal ideation using the Columbia Suicide Severity Rating Scale (C-SSRS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant either must have ceased lactating at screening or is still lactating actively breastfeeding at screening , must agree temporarily cease giving breast milk to her infant(s)
- •Participant has had a Major Depressive Episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
- •Participant was <12 months postpartum
- •Participant is amenable to intramuscular administration of investigational product on Day 1 and remaining inpatient until at least Day 4
排除标准
- •Active psychosis
- •Attempted suicide associated with current episode of postpartum depression
- •Medical history of seizures
- •Medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder
研究组 & 干预措施
BRII-296 + Depo Medrol
Participants will receive BRII-296 600 milligram (mg) and Depo Medrol (80 milligram per milliliter [mg/mL]) on Day 1 as a combination therapy.
干预措施: BRII-296 (Drug)
BRII-296 + Depo Medrol
Participants will receive BRII-296 600 milligram (mg) and Depo Medrol (80 milligram per milliliter [mg/mL]) on Day 1 as a combination therapy.
干预措施: Depo Medrol (Drug)
结局指标
主要结局
PK of Brexanolone: Area Under the Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last)
时间窗: Day 1- Day 45
Number of Participants With Adverse Events (AEs) According to Severity
时间窗: From the first dose of study drug up to Day 45
Severity will be assessed according to the following scale: Mild, moderate and severe.
Number of Participants With Change From Baseline in Clinically Significant Vital Sign Parameters
时间窗: Baseline up to Day 45
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters
时间窗: From the first dose of study drug up to Day 45
Number of Participants With Change From Baseline in Clinically Significant Clinical Laboratory Evaluations
时间窗: From the first dose of study drug up to Day 45
Change From Baseline in Glasgow Coma Scale (GCS) Score
时间窗: Baseline up to Day 45
The GCS is a simple measure of the depth and duration of impaired consciousness and coma. 3 domains of alertness will be evaluated: eye opening response (scored 1 \[None\] to 4 \[Spontaneous\]), verbal response (scored 1 \[None\] to 5 \[Oriented\]), and motor response (scored 1 \[None\] to 6 \[Obeys commands\]). Total scores range from 3 to 15, with 15 reflecting full alertness.
PK of Brexanolone: Maximum Observed Plasma Concentration (Cmax)
时间窗: Day 1- Day 45
PK of Brexanolone: Apparent Clearance (CL/F)
时间窗: Day 1- Day 45
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Responses
时间窗: Baseline up to Day 45
The suicidal ideation and behavior will be monitored during the study using the C-SSRS. This scale consists of a "Baseline/Screening" version that assesses the lifetime and recent experience of the participant with suicidal ideation and behavior, and a "Since Last Visit" version that focuses on suicidality since the last study visit. The C-SSRS includes "yes" or "no" responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe).
PK of Brexanolone: Time to Reach Cmax (Tmax)
时间窗: Day 1- Day 45
Change From Baseline in Stanford Sleepiness Scale (SSS) Score
时间窗: Baseline up to Day 45
The SSS is a participant-rated measure of sleepiness, frequently used for both research and clinical purposes. The SSS evaluates sleepiness at specific moments in time. Respondents rate their current degree of sleepiness and alertness on a scale of 1 to 7, where the lowest score of '1' indicates the respondent is 'feeling active, vital, alert, or wide awake' and the highest score of '7' indicates the respondent is 'no longer fighting sleep, sleep onset soon; having dream-like thoughts'.
PK of Brexanolone: Volume of Distribution (Vz/F)
时间窗: Day 1- Day 45
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From the first dose of study drug up to Day 45
PK of Brexanolone: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf)
时间窗: Day 1- Day 45
PK of Brexanolone: Apparent Terminal Elimination Half-life (t½)
时间窗: Day 1- Day 45
次要结局
- Number of Participants With HAM-D Response(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)
- Change From Baseline in Hamilton Depression Rating Scale (HAM-D) Total Score(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)
- Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)
- Number of Participants With Clinical Global Impression - Improvement (CGI-I) Response(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)
- Change From Baseline in Clinical Global Impression - Severity (CGI-S) Response(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)
- Change From Baseline in HAM-D Bech-6 Subscale Score(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)
- Number of Participants With HAM-D Remission(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)
- Change From Baseline in HAM-D Individual Item Score(Baseline and at Days 2, 3, 4, 8, 15, 30, and 45)