Efavirenz and Ritonavir on Human Brain P-Glycoprotein

Influence of Efavirenz and Ritonavir on Human Brain P-Glycoprotein Activity Using PET Imaging

To determine the effects of ritonavir and efavirenz on the activity of P-glycoprotein in human brain.

Study Overview

• Status: Completed
• Conditions: Drug Effects
• Intervention / Treatment: Drug: [11C] desmethyl-loperamide; Other: Control - no pretreatment; Drug: Oral ritonavir; Drug: Oral efavirenz

Detailed Description

Sequential crossover using tracer 11C-desmethylloperamide, a substrate for brain P-glycoprotein, and positron emission tomography (PET), administered after nothing (control), oral ritonavir (3d), and oral efavirenz (14d) with washout in between

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; 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: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant female, 18-40 yr old
• Good general health with no remarkable medical conditions
• BMI < 33
• Provide informed consent

Exclusion Criteria:

• Known history of liver or kidney disease
• History of major medical conditions
• HIV seropositive
• Fasting blood glucose > 110 mg/dl
• Family history of type 2 diabetes
• Use of prescription or non prescription medications, herbals or foods known to be metabolized by or altering P-glycoprotein or CYP3A activity (hormonal birth control medications are acceptable if alternative means of contraception are used)
• Females who are pregnant or nursing
• Females taking hormonal contraceptives who are unwilling to use alternative means of contraception
• Contraindications to MRI
• Contraindications to PET scanning

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control; Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging	Drug: [11C] desmethyl-loperamide; IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging; Other: Control - no pretreatment; Session 1: IV administration of 10-14 mCi [11C] desmethyl-loperamide (dLop) with PET/CT imaging and brain MRI
Active Comparator: Oral ritonavir; Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging	Drug: [11C] desmethyl-loperamide; IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging; Drug: Oral ritonavir; Session 2: Pretreatment with oral ritonavir for 3 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI
Active Comparator: Oral efavirenz; Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging	Drug: [11C] desmethyl-loperamide; IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging; Drug: Oral efavirenz; Session 3: Pretreatment with oral efavirenz for 14 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cerebral [11C]dLop Distribution Volume	1 day

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Evan Kharasch, MD, PhD., Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: July 30, 2012
• First Submitted That Met QC Criteria: August 15, 2012
• First Posted (Estimate): August 17, 2012

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Healthy volunteers; PET Imaging; Efavirenz; Ritonavir; [11C] desmethyl-loperamide
• 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; Gastrointestinal 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; Loperamide; Antidiarrheals
• Other Study ID Numbers: 201205135