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

• ClinicalTrials.gov Identifier: NCT01903824
• Recruitment Status: Completed
• First Posted: July 19, 2013
• Last Update Posted: April 3, 2014
• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Information provided by (Responsible Party): Teva Branded Pharmaceutical Products R&D, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cognitive Impairment	Drug: CEP-26401; Drug: donepezil hydrochloride; Drug: modafinil; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Official Title: 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
• Study Start Date: August 2013
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

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 Name: 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 Name: Irdabisant; Drug: donepezil hydrochloride; Donepezil hydrochloride, two 5 mg tablets, each over-encapsulated; Other Name: Aricept; Drug: Placebo; Placebos formulated to match each active drug
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 Name: Irdabisant; Drug: modafinil; modafinil 200 mg tablet, over-encapsulated; Other Name: Provigil; Drug: Placebo; Placebos formulated to match each active drug

Outcome Measures

Primary Outcome Measures :

1. Paired Associate Learning (PAL) Test [ Time Frame: Baseline to Hour 22 ]
2. Rapid Visual Information Processing (RVIP) Test [ Time Frame: Baseline to Hour 22 ]
3. Spatial Working Memory Test [ Time Frame: Baseline to Hour 22 ]
4. Stop Signal Task (SST) [ Time Frame: Baseline to Hour 22 ]
5. Adaptive tracking Test [ Time Frame: Baseline to Hour 22 ]
6. Body sway Test [ Time Frame: Baseline to Hour 22 ]
7. Leeds Sleep Evaluation Questionnaire (LSEQ) [ Time Frame: Baseline to Hour 22 ]
8. Leiden Maze Test (LMT) [ Time Frame: Baseline to Hour 22 ]
9. n-Back Working Memory Test [ Time Frame: Baseline to Hour 22 ]
10. Polysomnography (PSG) Test [ Time Frame: Baseline to Hour 22 ]
11. Saccadic Eye Movements [ Time Frame: Baseline to Hour 22 ]
12. Single-Choice Reaction Time [ Time Frame: Baseline to Hour 22 ]
13. Smooth Pursuit Eye Movements [ Time Frame: Baseline to Hour 22 ]
14. Visual Analog Scales (VAS) [ Time Frame: Baseline to Hour 22 ]
    Factors ranging from 'not at all' to 'extremely' are used to quantify subjective drug effects

Secondary Outcome Measures :

1. area under the drug concentration-time curve (AUC0-t) [ Time Frame: Baseline to Hour 22 ]
2. maximal observed plasma drug concentration (Cmax) [ Time Frame: Baseline to Hour 22 ]
3. time to maximum observed plasma drug concentration (tmax) [ Time Frame: Baseline to Hour 22 ]
4. Summary of participants with Adverse Events [ Time Frame: From signing of the consent form to Day 30 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Netherlands

Teva Investigational Site 38051

Leiden, Netherlands

Sponsors and Collaborators

Teva Branded Pharmaceutical Products R&D, Inc.

More Information

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT01903824
• Other Study ID Numbers: C26401/1111; 2013-001883-51 ( EudraCT Number )
• First Posted: July 19, 2013
• Last Update Posted: April 3, 2014
• Last Verified: April 2014

Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.:

Irdabisant; cognitive impairment

Additional relevant MeSH terms:

Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Modafinil; Donepezil; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Nootropic Agents; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers