A Double-Blind, Placebo-Controlled Evaluation of the Dexmedetomidine Transdermal Systems for Agitation Associated With Dementia of the Alzheimer's Type
概览
- 阶段
- 2 期
- 干预措施
- 12 cm2 - 2 Active DMTS Patches
- 疾病 / 适应症
- Agitation
- 发起方
- Teikoku Pharma USA, Inc.
- 入组人数
- 150
- 试验地点
- 6
- 主要终点
- Change in Agitated Behavior Scale (ABS) total score from baseline (Day -4 to Day -1 mean score) to the 96 hours of first application (Day 1 to Day 4).
- 状态
- 招募中
- 最后更新
- 19天前
概览
简要总结
The primary objective of this study is to evaluate the efficacy of DMTS on frequency and severity of agitation associated with dementia of the Alzheimer's type, compared with placebo.
详细描述
This is a randomized, double-blind, placebo-controlled, two application study of DMTS or matching placebo over a 4-day treatment period, followed 14 days later with the same treatment (active or placebo) for an additional 4-day treatment period for subjects that are eligible for second dosing. Eligible subjects will be screened up to 21 days prior to study start. Eligible subjects will be randomized 1:1:1 to treatment with 1 DMTS and 1 matching placebo, 2 DMTS, or 2 matching placebos.
研究者
入排标准
入选标准
- •Voluntarily provide written informed consent (subject or legally authorized representative \[LAR\]).
- •Male or female, residing in a care facility.
- •Has a diagnosis of dementia of probable Alzheimer's Disease (AD) based on National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria (2018). The clinical diagnosis of "probable Alzheimer's Disease (AD)" will be based on the 2018 National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria, which includes patient biomarker data as part of the research diagnosis (Jack et al., 2018). If patient biomarker data are unavailable, per the 2018 NIA-AA diagnostic criteria, the clinical diagnosis of probable AD will be based on the 2011 NIA-AA criteria (McKhann et al., 2011).
- •Had two or more episodes (using a 7-day lookback period) of agitation that impairs social activities, requires staff or medical intervention, or impairs ability for functional activities of daily living at Screening.
- •Had an ABS total score ≥ 22 at least once during Day -4 to Day -1 when assessing eligibility on Day 1 Pre-randomization.
- •Has gone a minimum of 1 week with no change in medication prior to Screening.
- •Has a score of ≤ 23 on the Mini-Mental State Examination (MMSE) at Screening.
- •Female subjects who are:
- •Not pregnant, not lactating, and not planning to become pregnant during the study or for 1 menstrual cycle thereafter and
- •Surgically sterile; or postmenopausal (ie, amenorrhea for ≥2 years as reported by subject/caregiver; postmenopausal status will be confirmed with FSH test); or have a monogamous partner who is surgically sterile; or have a same gender sex partner; or is using double-barrier contraception; or practicing abstinence; or using an insertable, injectable, transdermal, or combination oral contraceptive for 3 months prior to the study, during the study, and for 1 month following the study.
排除标准
- •Has a known sensitivity to dexmedetomidine or any excipient in the DMTS/placebo.
- •Has a skin abnormality (eg, scar, tattoo) or unhealthy skin condition (eg, burns, wounds) at the DMTS/matching placebo application site, according to examination by the investigator at screening.
- •Has a clinically significant abnormal clinical laboratory test value as determined by the investigator.
- •Has agitation caused by acute intoxication.
- •Has significant risk of suicide or homicide per investigator's assessment, or any patient with an answer of "yes" to Items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Has a history of or positive test results for the human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- •Has a clinically significant history or clinically significant manifestation of any of the following, as determined by the investigator: a renal (including an estimated glomerular filtration rate \[eGFR\] below the appropriate age- and gender-specific range \[see Section 8.1.3.2\]), hepatic (including any evidence of ascites and/or a Child-Pugh hepatic impairment score \> 6 \[Appendix G\]), cardiovascular, metabolic, neurologic, or psychiatric condition; congestive heart failure, peptic ulcer, gastrointestinal bleeding, or other condition that may preclude participation in the study.
- •Has a history of physician-diagnosed migraine, frequent non-vascular headaches (\> 5 per month), seizures, or are currently taking anticonvulsants.
- •Has a history of syncope or other syncopal attacks.
- •Has present and/or significant history of postural hypotension (determined through examination by the investigator or designee) or history of severe dizziness or fainting on standing in the opinion of the investigator.
研究组 & 干预措施
12 cm2 - 2 Active DMTS Patches
2 Active DMTS patches will be applied to the upper back and worn for 4 days (96 hours) followed 14 days later with the same treatment for an additional 4-day treatment for subjects that are eligible for a second dosing.
干预措施: 12 cm2 - 2 Active DMTS Patches
6 cm2 - 1 Active and 1 Placebo DMTS Patches
1 Active and 1 Placebo DMTS patches will be applied to the upper back and worn for 4 days (96 hours) followed 14 days later with the same treatment for an additional 4-day treatment period for subjects that are eligible for a second dosing.
干预措施: 6 cm2 - 1 Active and 1 Placebo DMTS Patches
Placebo - 2 Placebo DMTS Patches
2 Placebo DMTS patches will be applied to the upper back and worn for 4 days (96 hours) followed 14 days later with the same treatment for an additional 4-day treatment period for subjects that are eligible for a second dosing.
干预措施: Placebo - 2 Placebo DMTS Patches
结局指标
主要结局
Change in Agitated Behavior Scale (ABS) total score from baseline (Day -4 to Day -1 mean score) to the 96 hours of first application (Day 1 to Day 4).
时间窗: Baseline (Day -4 to Day -1) to 96 hours after first application (Day 1 to Day 4)
The ABS \[5\] is a 14-item scale developed to allow objective assessment of agitated behavior, particularly serial assessments for the evaluation of interventions to reduce agitation. The ABS Total Score ranges from 14 to 56. A total score of 21 or less is considered Normal; 22 to 28 is considered Mild; 29 to 35 Moderate; and 36 or more Severe Agitation.
次要结局
- Change in Clinical Global Impression Scale - Severity (CGI-S) score at 96 hours post-application (Day 5) relative to Pre-randomization (Day 1) baseline.(Day1 (Pre-randomization), Day 5)
- Change in CGI-S score at 168 hours post application (Day 8) relative to Day 1 Pre-randomization baseline.(Day1 (Pre-randomization), Day 8)
- Change in ABS total score from baseline (Day -4 to Day -1 mean score) to the 168 hours post first application (Day 1 to Day 7).(From Day -4 through Day 7)
- Percentage of subjects meeting the criteria for Day 15 DMTS/placebo application.(Day 15)
- Change from Pre-randomization Day 1 baseline score (Day -7 to Day -1 lookback) to 168 hours post application score (Day 1 to Day 7 lookback) in the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH).(Day -7, Day 7)