This trial is active, not recruiting.

Condition to evaluate two paradigms for simultaneous assessment of hepatic and intestinal cyp3a activity
Treatments grapefruit juice, delayed alfentanil, concomitant alfentanil
Sponsor Washington University School of Medicine
Start date October 2009
End date September 2016
Trial size 40 participants
Trial identifier NCT01008059, 09-0715, 5 RO1 GM063674-07


To evaluate two paradigms for simultaneous assessment of hepatic and intestinal CYP3A activity.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacodynamics study
Intervention model crossover assignment
Masking single blind (subject)
Primary purpose basic science
Control (no pretreatment), liver and gut CYP3A induction (rifampin 500 mg daily for 5d), liver and gut CYP3A inhibition (ketoconazole 400 mg daily for 3d), gut only CYP3A inhibition (grapefruit juice the night before and morning of study days)
grapefruit juice rifampin ketoconazole
grapefruit juice consumed within 24 hours of inducing CYP3A liver activity rifampin 500mg daily for 5 days ketoconazole 400 mg daily for 3 days
Alfentanil (0.5-1 mg IV bolus) followed 3 hours later by 1-4 mg oral deuterium-labeled (d3) alfentanil on each study visit.
delayed alfentanil alfentanil bolus labeled alfentanil
Alfentanil bolus .5-1.0mg IV, then labeled alfentanil administered orally 4 hours later
Alfentanil (0.5-1 mg IV bolus) together with 1-4 mg oral deuterium-labeled (d3) alfentanil on each study visit.
concomitant alfentanil alfentanil plus labeled alfentanil
Alfentanil .5-1.0 mg IV + labeled alfentanil one time bolus

Primary Outcomes

Primary outcome is the area under the curve of alfentanil concentration vs. time.
time frame: 12 hours

Eligibility Criteria

Male or female participants from 18 years up to 40 years old.

Inclusion Criteria: - Male or non-pregnant female, 18-40 yr. old - Good general health with no remarkable medical conditions such as liver, kidney, heart, or lung failure - BMI between 20-33 - Provide informed consent Exclusion Criteria: - Known history of liver or kidney disease - Use of prescription or non prescription medications, herbals or foods known to be metabolized by or affect CYP3A (including oral birth control medications) - Females who are pregnant or nursing - Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction) - Direct physical access to and routine handling of addicting drugs in the regular course of duty (this is a routine exclusion from studies of drugs with addiction potential). - History of bradycardia - Respiratory rate <10 - History of significant pulmonary disease - History of pre-existing medical condition predisposing to respiratory depression - Systolic blood pressure <100 mgHg and diastolic blood pressure <70mmHg

Additional Information

Official title Novel Noninvasive Assessment of Cytochrome P4450 Activity: Simultaneous Testing Pilot
Principal investigator Evan D Kharasch, MD, PhD
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Washington University School of Medicine.