A Five-Period, Placebo-Controlled, Crossover Study to Evaluate the Effect of Donepezil and MK-3134 on Reversal of Cognitive Impairment Associated With a Single-Dose of Scopolamine.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 主要终点
- CogState Early Phase Battery, Groton Maze Learning Test (GMLT) as measured by the number of errors on the GMLT over time (area under the GMLT-time curve) over hours 1-12.
研究概览
简要总结
The drug, scopolamine, can result in short-term impairments of cognitive function, attention, and memory that resemble those seen in aging and Alzheimer's disease. This study tested the capability of both individual and combined doses of MK-3134 and the current standard treatment: donepezil (Aricept), to reverse such impairments, following a single dose of scopolamine. Participants were evaluated after each of 5 different treatment periods (in a cross-over, double-dummy design): A: placebo to match both donepezil (oral [PO]) and MK-3134 (PO) followed by placebo scopolamine (subcutaneous [SQ]); B: placebo to match both donepezil (PO) and MK-3134 (PO), followed by scopolamine SQ; C: MK-3134 (PO) followed by scopolamine SQ; D: donepezil (PO) followed by scopolamine SQ; E: MK-3134 (PO) and donepezil (PO) followed by scopolamine SQ. The doses of MK3134, donepezil, and scopolamine were the same over all treatment arms in which the specified drug was administered. There were 8 total visits for each treatment period, including 5 Treatment Visits requiring 14-day intervals between visits for study-drug washout. Participants were assessed for cognitive function before and after each treatment period during the Treatment Visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Participants were eligible for inclusion in the study who were:
- •Male between 18 and 40 years of age.
- •Non-smokers, in good health (as defined in protocol), and were willing to follow study-related procedures.
- •Participants were not eligible for inclusion in the study if they:
- •Had a history of illness that, in the opinion of the study investigator or as specified in protocol, might confound the results of the study or posed an potential, additional risk to the participant if they were to participate in the study.
- •Were taking any medication (prescription, nonprescription, vitamin supplements or herbal, illicit or legitimate) except for acetaminophen.
- •Had a history of any significant head injury/trauma.
排除标准
- 未提供
研究组 & 干预措施
A, B, D, E, C
Participants received treatment A, B, D, E, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
A, B, D, E, C
Participants received treatment A, B, D, E, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
A, B, D, E, C
Participants received treatment A, B, D, E, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
A, B, D, E, C
Participants received treatment A, B, D, E, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
A, B, D, E, C
Participants received treatment A, B, D, E, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
B, C, E, A, D
Participants received treatment B, C, E, A, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
B, C, E, A, D
Participants received treatment B, C, E, A, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
B, C, E, A, D
Participants received treatment B, C, E, A, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
B, C, E, A, D
Participants received treatment B, C, E, A, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
B, C, E, A, D
Participants received treatment B, C, E, A, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
C, D, A, B, E
Participants received treatment C, D, A, B, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
C, D, A, B, E
Participants received treatment C, D, A, B, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
C, D, A, B, E
Participants received treatment C, D, A, B, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
C, D, A, B, E
Participants received treatment C, D, A, B, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
C, D, A, B, E
Participants received treatment C, D, A, B, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
D, E, B, C, A
Participants received treatment D, E, B, C, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
D, E, B, C, A
Participants received treatment D, E, B, C, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
D, E, B, C, A
Participants received treatment D, E, B, C, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
D, E, B, C, A
Participants received treatment D, E, B, C, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
D, E, B, C, A
Participants received treatment D, E, B, C, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
E, A, C, D, B
Participants received treatment E, A, C, D, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
E, A, C, D, B
Participants received treatment E, A, C, D, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
E, A, C, D, B
Participants received treatment E, A, C, D, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
E, A, C, D, B
Participants received treatment E, A, C, D, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
E, A, C, D, B
Participants received treatment E, A, C, D, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
A, C, B, E, D
Participants received treatment A, C, B, E, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
A, C, B, E, D
Participants received treatment A, C, B, E, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
A, C, B, E, D
Participants received treatment A, C, B, E, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
A, C, B, E, D
Participants received treatment A, C, B, E, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
A, C, B, E, D
Participants received treatment A, C, B, E, D for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
B, D, C, A, E
Participants received treatment B, D, C, A, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
B, D, C, A, E
Participants received treatment B, D, C, A, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
B, D, C, A, E
Participants received treatment B, D, C, A, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
B, D, C, A, E
Participants received treatment B, D, C, A, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
B, D, C, A, E
Participants received treatment B, D, C, A, E for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
C, E, D, B, A
Participants received treatment C, E, D, B, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
C, E, D, B, A
Participants received treatment C, E, D, B, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
C, E, D, B, A
Participants received treatment C, E, D, B, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
C, E, D, B, A
Participants received treatment C, E, D, B, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
C, E, D, B, A
Participants received treatment C, E, D, B, A for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
D, A, E, C, B
Participants received treatment D, A, E, C, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
D, A, E, C, B
Participants received treatment D, A, E, C, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
D, A, E, C, B
Participants received treatment D, A, E, C, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
D, A, E, C, B
Participants received treatment D, A, E, C, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
D, A, E, C, B
Participants received treatment D, A, E, C, B for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
E, B, A, D, C
Participants received treatment E, B, A, D, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine (Drug)
E, B, A, D, C
Participants received treatment E, B, A, D, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg (Drug)
E, B, A, D, C
Participants received treatment E, B, A, D, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: C: MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
E, B, A, D, C
Participants received treatment E, B, A, D, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: D: Donepezil 10 mg + Scopolamine 0.5 mg (Drug)
E, B, A, D, C
Participants received treatment E, B, A, D, C for Periods 1, 2, 3, 4, and 5, respectively.
干预措施: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg (Drug)
结局指标
主要结局
CogState Early Phase Battery, Groton Maze Learning Test (GMLT) as measured by the number of errors on the GMLT over time (area under the GMLT-time curve) over hours 1-12.
时间窗: 1, 2, 3, 4, 6, 8, and 12 hours relative to administration of SQ scopolamine or SQ placebo
Participants learned a hidden pathway through a maze (10 x 10 grid of tiles on a computer touch screen) using step-by-step guess, with trial and error feedback after each step. Once the pathway was learned, participants repeated the same pathway four more times. The number of pathway errors was used to indicate the level of cognitive function.
次要结局
未报告次要终点