Efavirenz and Ritonavir on Human Brain P-Glycoprotein

The Washington University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Drug Effects

Treatments: Drug: Oral efavirenz; Drug: Oral ritonavir; Other: Control - no pretreatment; Drug: [11C] desmethyl-loperamide

Study type: Interventional

Funder types: Other

Identifiers

NCT01668147

201205135

Details and patient eligibility

About

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

Full 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

Enrollment: 13 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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13 participants in 3 patient groups

Control

Experimental group

Description:

Session 1: Control (no pretreatment) - IV 10-14 mCi of \[11C\] desmethyl-loperamide (dLop) with PET/CT imaging

Treatment:

Drug: [11C] desmethyl-loperamide

Other: Control - no pretreatment

Oral ritonavir

Active Comparator group

Description:

Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of \[11C\]dLop with PET/CT imaging

Treatment:

Drug: Oral ritonavir

Drug: [11C] desmethyl-loperamide

Oral efavirenz

Active Comparator group

Description:

Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of \[11C\]dLop with PET/CT imaging

Treatment:

Drug: Oral efavirenz

Drug: [11C] desmethyl-loperamide