PET Study Examining the Dopaminergic Activity of Armodafinil in Adults

NCT00592943 | Completed Phase 1 Results

• 1 other identifier: 2007-P-001659
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The specific aims of this study are 1) to document the Dopamine Transporter (DAT) receptor occupancy of armodafinil using positron emission tomography (PET) scanning with C-11 altropane as the ligand and 2) to document the increased intrasynaptic dopamine produced by armodafinil using PET scanning with C-11 raclopride as the ligand. We hypothesize that DAT occupancy will be low with armodafinil; less than the DAT occupancy produced by therapeutic doses of methylphenidate. We also hypothesize that increases in intrasynaptic dopamine will be relatively low with armodafinil.

Conditions

Healthy

Keywords

Adults; Healthy Volunteers; Nuvigil; Armodafinil; DAT occupancy in healthy volunteers

Outcome Measures

Primary Outcomes (3)

• Armodafinil DAT Occupancy in Caudate

  Subjects received each dose level (100 and 250 mg) of armodafinil, followed by PET scans, in an open-label protocol. Repeat PET scans, using \[1 1 C\]altropane, determined DAT occupancy at 1 hour and 2.5 hours postdose (compared with baseline).

  DAT occupancy was measured using the PET scan at 1 hour and 2.5 hours after oral administration of 100mg or 250 mg Armodafinil

• Armodafinil Extracellular Dopamine in Caudate at 2.5 Hours (With Outlier)

  Each subject received each dose level (one dose per day of 100 or 250 mg) of armodafinil, followed by PET scans using \[11C\]raclopride, to determine the change in extracellular dopamine at 2.5 hours postdose.

  Extracellular DAT was measured using the PET scan at 2.5 hours after oral administration of 100mg or 250 mg Armodafinil on three different study visits

• Armodafinil Extracellular Dopamine in Caudate at 2.5 Hours (Without Outlier)

  Each subject received each dose level (one dose per day of 100 or 250 mg) of armodafinil, followed by PET scans using \[11C\]raclopride, to determine the change in extracellular dopamine at 2.5 hours postdose.

  Extracellular DAT was measured using the PET scan at 2.5 hours after oral administration of 100mg or 250 mg Armodafinil on three different study visits

Study Arms (2)

Armodafinil (100mg)

ACTIVE COMPARATOR

Drug: armodafinil

Armodafinil (250 mg)

ACTIVE COMPARATOR

Drug: armodafinil

Interventions

armodafinil DRUG

tablet, taken by mouth, once each study day

Also known as: Nuvigil

Armodafinil (100mg); Armodafinil (250 mg)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed written informed consent to participate in the study.
• Age: 18 - 35
• If female, non-pregnant, non-nursing with a negative serum pregnancy test and using an adequate form of birth control.
• Supine and standing blood pressure within the range 110/60 to 150/95 mmHg.
• Heart rate, after resting for 5 minutes, within the range 46-90 beats/min.
• Right-handed.

You may not qualify if:

• Diagnosis of any psychotic disorder, bipolar disorder, severe depression, severe anxiety, or Autism.
• Subjects with mild mood, oppositional, conduct, and anxiety disorders may be permitted to participate if considered appropriate by the investigator.
• Scores of Baseline Scales:
• Hamilton Depression Scale \> 17 (out of a possible 67 on the 21-item scale)(Hamilton 1960) Beck Depression Inventory \> 19 (out of a possible 63 on the 21-item scale)(Beck, Ward et al. 1961) Hamilton Anxiety Scale \> 21 (out of a possible 56 on the 14-item scale) (Hamilton 1959)
• Tics or Tourette's Syndrome.
• History of head trauma with loss of consciousness, organic brain disorders, seizures, or neurosurgical intervention.
• Any clinically significant chronic medical condition, in the judgment of the investigator.
• Mental impairment as evidenced by an I.Q. \<75.
• Exposure to dopamine receptor antagonists within the previous three (3) months.
• Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan.
• Subjects receiving psychotropic medication.
• Any clinically significant abnormality in the screening laboratory tests, vital signs, or 11-lead ECG, outside of normal limits.
• Any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant.
• Subjects with a known recent history (within the past six (6) months) of illicit drug or alcohol dependence.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Cambridge, Massachusetts, 02138, United States

Location

Related Publications (1)

• Spencer TJ, Madras BK, Bonab AA, Dougherty DD, Clarke A, Mirto T, Martin J, Fischman AJ. A positron emission tomography study examining the dopaminergic activity of armodafinil in adults using [(1)(1)C]altropane and [(1)(1)C]raclopride. Biol Psychiatry. 2010 Nov 15;68(10):964-70. doi: 10.1016/j.biopsych.2010.08.026.

  PMID: 21035624 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Modafinil

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Extracellular dopamine could compete with \[11C\] altropane, causing an overestimation of DAT occupancy. Time between scans and menstrual cycle could be sources of variability. Brain pathology although unlikely in normal subjects, is possible.

Results Point of Contact

• Title: Thomas J. Spencer, MD
• Organization: Massachusetts General Hospital; Harvard Medical School

tspencer@partners.org

(617) 726-1731

Study Officials

• Thomas Spencer, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief, Clinical and Research Program, Pediatric Psychopharmacology

Study Record Dates

• First Submitted: December 28, 2007
• First Posted: January 14, 2008
• Study Start: October 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2010
• Last Updated: November 13, 2013
• Results First Posted: June 10, 2011

Record last verified: 2013-10

Locations

US (1)