LAAM-HAART PET Imaging

Efavirenz and Ritonavir Influence on Human Brain Levo-acetylmethadol (LAAM) Disposition Assessed Using PET Imaging

The purpose of this study is to determine the effects of the antiretroviral drugs efavirenz and ritonavir on human brain LAAM disposition in vivo.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Radiation: [11c] LAAM; Drug: Ritonavir; Drug: Efavirenz

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

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

Each subject must meet all of the following criteria:

1. Male or non-pregnant female volunteer, 18-50 yr old
2. Good general health with no known major medical conditions
3. BMI < 33
4. Provide informed consent

Exclusion Criteria

Subjects will not be enrolled if any of the following criteria exist:

1. Known history of liver or kidney disease
2. History of major medical conditions
3. HIV seropositive
4. Fasting blood glucose > 110 mg/dl (because HAART can cause glucose intolerance)
5. Family history of type 2 diabetes
6. Use of prescription or non prescription medications, herbals or foods known to be metabolized by or altering P-glycoprotein or CYP3A (hormonal birth control medications are acceptable if alternative means of contraception are used)
7. Females who are pregnant or nursing
8. Females taking hormonal contraceptives who are unwilling to use alternative means of contraception
9. Contraindications to MRI (e.g., metal implants or splinters in the body; a worn or implanted medical device, such as a pacemaker or drug pump; inability to lie flat for up to one hour; claustrophobia) or contraindications to PET scanning (e.g., inability to lie flat for up to one hour, claustrophobia, current
10. Current or recent (within 12 months prior to screening) participation in research studies involving radiation exposure such that the total research-related radiation dose to the subject in any given year would exceed the limits set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1 (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361.1))

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LAAM arm; [11C]LAAM 15-20 mCi (maximum administered mass of 10 ug); Efavirenz, oral capsules, 600 mg; Ritonavir, oral capsules, 100 mg

Radiation: [11c] LAAM; intravenous administration of 15-20 mCi of [11c] LAAM.; Drug: Ritonavir; Pretreatment with oral ritonavir for 3 days followed by intravenous administration of 15-20 mCI of [11c] LAAM.; Other Names: Kaletra; Drug: Efavirenz; Pretreatment with oral Efavirenz 600 mg orally every night x 14 days followed by intravenous administration of 15-20 mCI of [11c] LAAM.; Other Names: Sustiva, Atripla

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cerebral [11C]LAAM distribution volume	Blood tests, MRI and PET data analysis and interpretation	approximately 3 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 30, 2013
• First Submitted That Met QC Criteria: August 30, 2013
• First Posted (Estimate): September 5, 2013

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Healthy volunteers; PET Imaging; Efavirenz; Ritonavior [11C] LAAM
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Ritonavir; Efavirenz
• Other Study ID Numbers: 201307040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No