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

NCT01903824 | Completed Phase 1

• 2 other identifiers: C26401/11112013-001883-51
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Impairment

Keywords

Irdabisant; cognitive impairment

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (4)

• 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

Study Arms (3)

CEP-26401 5 μg, 25 μg, 125 μg, placebo

EXPERIMENTAL

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; Drug: Placebo

CEP-26401 5 μg, 25 μg, placebo, donepezil

EXPERIMENTAL

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; Drug: donepezil hydrochloride; Drug: Placebo

CEP-26401 5 μg, 125 μg, placebo, modafinil

EXPERIMENTAL

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; Drug: modafinil; Drug: Placebo

Interventions

CEP-26401 DRUG

CEP-26401 as an oral solution at the assigned dose of 5, 25 and/or 125 μg.

Also known as: Irdabisant

CEP-26401 5 μg, 125 μg, placebo, modafinil; CEP-26401 5 μg, 25 μg, 125 μg, placebo; CEP-26401 5 μg, 25 μg, placebo, donepezil

donepezil hydrochloride DRUG

Donepezil hydrochloride, two 5 mg tablets, each over-encapsulated

Also known as: Aricept

CEP-26401 5 μg, 25 μg, placebo, donepezil

modafinil DRUG

modafinil 200 mg tablet, over-encapsulated

Also known as: Provigil

CEP-26401 5 μg, 125 μg, placebo, modafinil

Placebo DRUG

Placebos formulated to match each active drug

CEP-26401 5 μg, 125 μg, placebo, modafinil; CEP-26401 5 μg, 25 μg, 125 μg, placebo; CEP-26401 5 μg, 25 μg, placebo, donepezil

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Teva Investigational Site 38051

Leiden, Netherlands

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

6-(4-(3-(2-methylpyrrolidin-1-yl)propoxy)phenyl)-2H-pyridazin-3-one; Donepezil; Modafinil

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Benzhydryl Compounds; Benzene Derivatives

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 19, 2013
• Study Start: August 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 3, 2014

Record last verified: 2014-04

Locations

NL (1)