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

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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment
• Intervention / Treatment: Drug: CEP-26401; Drug: Placebo; Drug: donepezil hydrochloride; Drug: modafinil

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Teva Investigational Site 38051

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. 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.
3. The subject is a man or woman, 18 to 50 years of age, inclusive.
4. The subject has a body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive.
5. The subject has skin type I to IV (very light to olive).
6. The subject is in a good health as determined by medical history, ECG, vital signs, physical examination, and clinical laboratory tests.
7. 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.
8. The subject is able to complete the screening process within 4 weeks prior to study drug administration.

Exclusion Criteria:

1. The subject has a cognitive performance outside of reference values at screening.
2. The subject smokes, is a tobacco user, currently uses nicotine products.
3. The subject has a known hypersensitivity to donepezil, modafinil, irdabisant, or one of the excipients, or has any significant food or drug allergies.
4. The subject is a female who is pregnant or lactating.
5. The subject has an intraocular pressure greater than 22 mm Hg.
6. 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.

7. 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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CEP-26401 5 μg, 25 μg, 125 μg, placebo; 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; CEP-26401 as an oral solution at the assigned dose of 5, 25 and/or 125 μg.; Other Names: Irdabisant; Drug: Placebo; Placebos formulated to match each active drug
Experimental: CEP-26401 5 μg, 25 μg, placebo, donepezil; 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; CEP-26401 as an oral solution at the assigned dose of 5, 25 and/or 125 μg.; Other Names: Irdabisant; Drug: Placebo; Placebos formulated to match each active drug; Drug: donepezil hydrochloride; Donepezil hydrochloride, two 5 mg tablets, each over-encapsulated; Other Names: Aricept
Experimental: CEP-26401 5 μg, 125 μg, placebo, modafinil; 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; CEP-26401 as an oral solution at the assigned dose of 5, 25 and/or 125 μg.; Other Names: Irdabisant; Drug: Placebo; Placebos formulated to match each active drug; Drug: modafinil; modafinil 200 mg tablet, over-encapsulated; Other Names: Provigil

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 16, 2013
• First Submitted That Met QC Criteria: July 16, 2013
• First Posted (Estimate): July 19, 2013

Study Record Updates

• Last Update Posted (Estimate): April 3, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: cognitive impairment; Irdabisant
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Nootropic Agents; Cholinesterase Inhibitors; Wakefulness-Promoting Agents; Donepezil; Modafinil
• Other Study ID Numbers: C26401/1111; 2013-001883-51 (EudraCT Number)