A Randomized, Double-blind, Placebo-controlled, Single-dose, 6-Period Crossover Study to Evaluate the Effects of BPN14770 on Scopolamine-induced Cognitive Impairment in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Groton Maze Learning Test (GMLT)
研究概览
简要总结
This is a Phase 1, randomized, double-blind, placebo-controlled, 6-period crossover study to evaluate the effects of BPN14770 10 mg and 50 mg in reversing scopolamine-induced cognitive impairment in healthy volunteers. A positive control, donepezil 10 mg, will be included, and additivity of BPN14770 50 mg to donepezil 10 mg in reversing scopolamine effects will also be evaluated.
详细描述
A total of 38 subjects will be enrolled into the study. The study duration will be up to 12 weeks with 6 weeks of single-dose Treatment Visits. The study will consist of a Screening Visit (up to 28 days prior to first study drug administration), six inpatient Treatment Visits (Periods 1 through 6), and a Follow-Up/Early Termination Visit (7-10 days after the last dose of study medication). An additional study visit may be necessary to complete the required cognitive test familiarization if not completed during the Screening Visit. Each Treatment Visit will occur approximately one week apart, allowing a 6 to 8 day washout period.
Subjects will be randomized to 1 of 6 treatment sequences based on a computer-generated randomization schedule. Subjects will receive all 6 treatments as specified by the treatment sequence according to a 6 × 6 Williams Latin square design. The following treatments will be administered:
A. Scopolamine placebo + BPN14770 placebo + donepezil placebo
B. Scopolamine 0.5 mg + BPN14770 placebo + donepezil placebo
C. Scopolamine 0.5 mg + BPN14770 10 mg + donepezil placebo
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males or females between the ages of 18 to 55 years at Screening.
- •Body mass index between 18 kg/m2 to 33 kg/m2, inclusive, and body weight of >50 kg (110 pounds).
- •Female subjects must be surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to first study drug administration), at least two years post-menopausal, or willing to either (1) utilize hormonal contraception plus use one barrier method or (2) use two barrier methods of contraception from initial screening until one month after taking the final dose. Barrier methods of contraception include diaphragm, cervical cap, male condom, female condom, and spermicidal foam and sponges. An intrauterine device (IUD) is also considered a barrier method of contraception in this study; if the subject is using an IUD, she will need to use an additional barrier method of contraception. Menopausal status will be verified by testing for follicle stimulating hormone (FSH ≥25 mIU/mL) at Screening. In addition, all females must have a negative blood test for pregnancy within 28 days during the Screening period and negative urine test for pregnancy on Day-1 of each Treatment Visit regardless of childbearing potential.
- •Male subjects must be willing to inform female partners of their participation in the study and must agree to use adequate contraceptive methods (vasectomy performed at least 6 months prior to first study drug administration, or use at least one barrier method of birth control).
- •Able to understand the study procedures, voluntarily consent to participate in this study, and provide written informed consent prior to start of any study-specific procedures.
- •Willing and able to remain in the study unit for the required periods and return for each treatment of the six treatment periods, including the outpatient visits.
排除标准
- •Clinically significant abnormality, in the Investigator's judgement, in Screening hematology, chemistry, or urinalysis tests, or from medical history, social history, vital sign, or physical examination
- •Active liver disease or positive serology results for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
- •Abnormal liver function test at the Screening Visit (aspartate aminotransferase or alanine aminotransferase >2 × the upper limit of normal [ULN]; total bilirubin >1.5 × ULN; or alkaline phosphatase >2 × ULN based on appropriate age and gender normal values).
- •Current or past history of angle closure glaucoma, or diagnosis of angle closure glaucoma.
- •Marked hypotension (systolic blood pressure [BP] ˂90 mmHg or diastolic BP ˂50 mmHg) or hypertension (systolic BP ˃150 mmHg or diastolic BP ˃100 mmHg) based on sitting values obtained. Out-of-range results may be repeated once at Screening. This exclusion applies to the vital signs performed at Screening and on Day -1 on Treatment Period
- •Marked bradycardia (heart rate ˂45 beats per minute [bpm]) or tachycardia (heart rate ˃110 bpm) based on supine ECG values obtained. Out-of-range results may be repeated once at Screening. This exclusion applies to the vital signs performed at Screening and on Day -1 on Treatment Period
- •Current or past history of significant (in the Investigator's judgement) cardiovascular, cerebrovascular, pulmonary, renal, or liver disease. Stable, well-controlled hypertension and hyperlipidemias are allowed.
- •Clinically important or significant conduction abnormalities on single ECG or evidence or history of long QT syndrome based on supine ECG values obtained at Screening. Out-of-range results may be repeated once at Screening.
- •Current or past history of gastric or duodenal ulcers or other diseases of the gastrointestinal tract that could interfere with absorption of study drug. Note: Subjects with a history of appendectomy or cholecystectomy may be enrolled.
- •Active acute or chronic infectious diseases.
- •Unable to discontinue medications including anticholinergic agents, psychotropic drugs, sedative antihistamines, or other centrally active medications [e.g., CNS- penetrant beta blockers], and moderate to strong inhibitors or inducers of CYP3A4, CYP2D6, or other cytochromes) 14 days prior to the first dose of study drug (Period 1, Day 1) and during the study (Follow-Up). Other prescription or non-prescription drugs such as antihypertensive or cholesterol lowering drugs are allowed, if, in the Investigator's judgement, they would not interfere with the study medication or the cognitive testing.
- •Unable to discontinue and abstain from over-the-counter, herbal preparations, dietary supplements, nutraceuticals, vitamins and minerals at least 7 days prior to the first dose of study drug and during the study. The one exception to this rule is acetaminophen, which may be taken for minor ailments at doses up to 1000 mg per day.
- •Any history of alcohol or other substance abuse, including marijuana, within the previous year prior to the Screening visit (per the current edition of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5), or regular (daily) consumption of alcohol exceeding two bottles of beer, or the equivalent amount of other forms of alcohol (1 serving = 12 oz beer, 5.0 oz wine, or 1.5 oz distilled spirits).
- •Any use of alcohol, grapefruit, marijuana, or other psychotropic agent within 12 hours of admission into the CRU.
- •Active smokers or tobacco users (e.g., chew and snuff) who are unable to discontinue tobacco use or nicotine-containing products (including e-cigarettes) at least 4 weeks prior to Screening and to refrain from using during the study.
- •Inability or unwillingness to comply with the protocol or likely inability to complete the study.
- •Participation in other clinical studies involving investigational drug within the previous 30 days prior to the Screening Visit.
- •Donation of blood within the prior 4 weeks, or blood products within the prior 2 weeks, prior to first study drug administration.
- •Positive result for drugs of abuse, alcohol, or cotinine at Screening, or a positive drug or alcohol (breath) result upon admission to CRU.
- •History of clinically significant drug allergy that includes symptoms such as shortness of breath, rash, or edema. This includes known hypersensitivity to donepezil hydrochloride, scopolamine, or belladonna, alkaloids.
- •Inability or unwillingness to perform the Cogstate cognitive function tests.
- •A suicidal ideation intensity score of 2 or higher per screening Columbia Suicide Severity Rating Scale (C-SSRS) assessment and/or any suicidal behavior within the past 28 days.
研究组 & 干预措施
B) S:P:P
Scopolamine 0.5mg : BPN14770 placebo : Donepezil placebo
干预措施: BPN14770 placebo (Drug)
A) P:P:P
Scopolamine placebo : BPN14770 placebo : Donepezil placebo
干预措施: BPN14770 placebo (Drug)
A) P:P:P
Scopolamine placebo : BPN14770 placebo : Donepezil placebo
干预措施: Donepezil placebo (Drug)
A) P:P:P
Scopolamine placebo : BPN14770 placebo : Donepezil placebo
干预措施: Scopolamine placebo (Drug)
B) S:P:P
Scopolamine 0.5mg : BPN14770 placebo : Donepezil placebo
干预措施: Donepezil placebo (Drug)
B) S:P:P
Scopolamine 0.5mg : BPN14770 placebo : Donepezil placebo
干预措施: Scopolamine 0.6 MG/ML (Drug)
C) S:B:P
Scopolamine 0.5mg : BPN14770 10mg : Donepezil placebo
干预措施: BPN14770 (Drug)
C) S:B:P
Scopolamine 0.5mg : BPN14770 10mg : Donepezil placebo
干预措施: Donepezil placebo (Drug)
C) S:B:P
Scopolamine 0.5mg : BPN14770 10mg : Donepezil placebo
干预措施: Scopolamine 0.6 MG/ML (Drug)
D) S:B:P
Scopolamine 0.5mg : BPN14770 50mg : Donepezil placebo
干预措施: BPN14770 (Drug)
D) S:B:P
Scopolamine 0.5mg : BPN14770 50mg : Donepezil placebo
干预措施: Donepezil placebo (Drug)
D) S:B:P
Scopolamine 0.5mg : BPN14770 50mg : Donepezil placebo
干预措施: Scopolamine 0.6 MG/ML (Drug)
E) S:P:D
Scopolamine 0.5mg : BPN14770 placebo : Donepezil 10mg
干预措施: BPN14770 placebo (Drug)
E) S:P:D
Scopolamine 0.5mg : BPN14770 placebo : Donepezil 10mg
干预措施: Donepezil (Drug)
E) S:P:D
Scopolamine 0.5mg : BPN14770 placebo : Donepezil 10mg
干预措施: Scopolamine 0.6 MG/ML (Drug)
F) S:B:D
Scopolamine 0.5mg : BPN14770 50mg : Donepezil 10mg
干预措施: BPN14770 (Drug)
F) S:B:D
Scopolamine 0.5mg : BPN14770 50mg : Donepezil 10mg
干预措施: Donepezil (Drug)
F) S:B:D
Scopolamine 0.5mg : BPN14770 50mg : Donepezil 10mg
干预措施: Scopolamine 0.6 MG/ML (Drug)
结局指标
主要结局
Groton Maze Learning Test (GMLT)
时间窗: 2 hours post-scopolamine s.c. injection
次要结局
未报告次要终点