Pharmacokinetics and Pharmacodynamics (PK/PD) of CEP-26401 in Healthy Subjects

Study Overview
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Brief Summary
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This is a single center, double-blind, placebo and positive-controlled, randomized, partial 6-way cross-over study to investigate the pharmacodynamics and pharmacokinetics of CEP-26401 (5, 25, and 125 μg) following single-dose administration to healthy male and female subjects.

Official Title
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A Double-Blind, Placebo- and Positive-Controlled, Randomized, Partial 6-way Crossover Study to Investigate the Pharmacodynamics and Pharmacokinetics of CEP-26401 (5, 25, and 125 μg) Following Single-Dose Administration to Healthy Subjects

Conditions
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Cognitive Impairment

Intervention / Treatment
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* Drug: CEP-26401
* Drug: donepezil hydrochloride
* Drug: modafinil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is able to give legal informed consent and understand the requirements of the study and communicate with the investigator in the local spoken language. The subject is willing to comply with the study requirements (eg, all dietary, exercise, tobacco, and alcohol restrictions) and provide their written informed consent to participate in the study. The subject is a man or woman, 18 to 50 years of age, inclusive. The subject has a body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive. The subject has skin type I to IV (very light to olive). The subject is in a good health as determined by medical history, ECG, vital signs, physical examination, and clinical laboratory tests. Female subjects of childbearing potential must have a negative serum β-human chorionic gonadotropin (hCG) test (at screening) and check-in and be willing and able to use one of the protocol-specified double-barrier methods of birth control. The subject is able to complete the screening process within 4 weeks prior to study drug administration. Exclusion Criteria: The subject has a cognitive performance outside of reference values at screening. The subject smokes, is a tobacco user, currently uses nicotine products. The subject has a known hypersensitivity to donepezil, modafinil, irdabisant, or one of the excipients, or has any significant food or drug allergies. The subject is a female who is pregnant or lactating. The subject has an intraocular pressure greater than 22 mm Hg. The subject is suffering from, or has a clinically significant history of one or more of the following: cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), or a history of any illness that, in the opinion of the investigator, might pose additional risk to the subject by participation in the study or confound the results of the study. The subject has a laboratory abnormality judged by the investigator as clinically significant, or measurements outside of the defined range Other exclusion criteria apply; please contact the investigator for more information.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CEP-26401 5 μg, 25 μg, 125 μg, placebo<br>Participants are dosed four times during this cross-over study. This group takes three active interventions (CEP-26401 in each of the dose options: 5, 25 and 125 μg, and one dose that only contains the placebos.) | Drug: CEP-26401<br>* CEP-26401 as an oral solution at the assigned dose of 5, 25 and/or 125 μg.<br>* Other names: Irdabisant;Drug: Placebo<br>* Placebos formulated to match each active drug<br>|
| Experimental: CEP-26401 5 μg, 25 μg, placebo, donepezil<br>Participants are dosed four times during this cross-over study. This group takes three active interventions (CEP-26401 at 5 and 25 μg, and donepezil at 10mg and one dose that only contains the placebos.) | Drug: CEP-26401<br>* CEP-26401 as an oral solution at the assigned dose of 5, 25 and/or 125 μg.<br>* Other names: Irdabisant;Drug: donepezil hydrochloride<br>* Donepezil hydrochloride, two 5 mg tablets, each over-encapsulated<br>* Other names: Aricept;Drug: Placebo<br>* Placebos formulated to match each active drug<br>|
| Experimental: CEP-26401 5 μg, 125 μg, placebo, modafinil<br>Participants are dosed four times during this cross-over study. This group takes three active interventions (CEP-26401 at 5 and 125 μg, and modafinil at 200mg) and one dose that only contains the placebos.) | Drug: CEP-26401<br>* CEP-26401 as an oral solution at the assigned dose of 5, 25 and/or 125 μg.<br>* Other names: Irdabisant;Drug: modafinil<br>* modafinil 200 mg tablet, over-encapsulated<br>* Other names: Provigil;Drug: Placebo<br>* Placebos formulated to match each active drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paired Associate Learning (PAL) Test |  | Baseline to Hour 22 | 
| Rapid Visual Information Processing (RVIP) Test |  | Baseline to Hour 22 | 
| Spatial Working Memory Test |  | Baseline to Hour 22 | 
| Stop Signal Task (SST) |  | Baseline to Hour 22 | 
| Adaptive tracking Test |  | Baseline to Hour 22 | 
| Body sway Test |  | Baseline to Hour 22 | 
| Leeds Sleep Evaluation Questionnaire (LSEQ) |  | Baseline to Hour 22 | 
| Leiden Maze Test (LMT) |  | Baseline to Hour 22 | 
| n-Back Working Memory Test |  | Baseline to Hour 22 | 
| Polysomnography (PSG) Test |  | Baseline to Hour 22 | 
| Saccadic Eye Movements |  | Baseline to Hour 22 | 
| Single-Choice Reaction Time |  | Baseline to Hour 22 | 
| Smooth Pursuit Eye Movements |  | Baseline to Hour 22 | 
| Visual Analog Scales (VAS) | Factors ranging from 'not at all' to 'extremely' are used to quantify subjective drug effects | Baseline to Hour 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the drug concentration-time curve (AUC0-t) |  | Baseline to Hour 22 | 
| maximal observed plasma drug concentration (Cmax) |  | Baseline to Hour 22 | 
| time to maximum observed plasma drug concentration (tmax) |  | Baseline to Hour 22 | 
| Summary of participants with Adverse Events |  | From signing of the consent form to Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irdabisant, cognitive impairment