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Trial record 16 of 16 for:    " April 18, 2007":" May 18, 2007"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Drug Interaction Study of Lopinavir/Ritonavir and Gemfibrozil (GEM-PK)

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ClinicalTrials.gov Identifier: NCT00474201
Recruitment Status : Completed
First Posted : May 16, 2007
Results First Posted : April 9, 2012
Last Update Posted : September 26, 2016
Sponsor:
Information provided by (Responsible Party):
Scott Penzak, Pharm.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label)
Condition Healthy Volunteers
Interventions Drug: Lopinavir/Ritonavir
Drug: Gemfibrozil
Enrollment 15
Recruitment Details Up to 30 healthy volunteers will be screened to enroll a total of 15 healthy volunteers. We will actively encourage participation of all ethnic groups and females. Recruitment of HIV-negative volunteers will be done through the normal volunteer office at NIH.
Pre-assignment Details Subjects who meet inclusion criteria and do not meet any exclusion criteria will be invited to participate in the study.
Arm/Group Title Gemfibrozil (GF) Alone Followed by GF+ Lopinavir-ritonavir
Hide Arm/Group Description Subjects received a single 600 mg dose of gemfibrozil before and after receiving lopinavir-ritonar 400mg/100mg twice daily, for 14.5 days. After each gemfibrozil dose, blood samples were collected to determine gemfibrozil plasma concentrations. These plasma concentrations were then used to determine gemfibrozil pharmacokinetic (PK) parameter values such as area under the concentration vs. time curve (AUC). Gemfibrozil PK parameter values were then compared before- and after lopinavir-ritonavir administration.
Period Title: Overall Study
Started 15
Completed 15
Not Completed 0
Arm/Group Title Gemfibrozil (GF) Alone Followed by GF + Lopinavir-ritonavir
Hide Arm/Group Description Subjects received a single 600 mg dose of gemfibrozil before- and after receiving lopinavir-ritonar 400mg/100mg twice daily, for 14.5 days. After each gemfibrozil dose, blood samples were collected for the determination of gemfibrozil plasma concentrations. The plasma concentrations were then used to determine gemfibrozil pharmacokinetic (PK) parameters values such as area under the concentration vs. time curve (AUC). PK Parameter values were then compared pre- and post lopinavir-ritonavir administration.
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
37  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
7
  46.7%
Male
8
  53.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
1.Primary Outcome
Title Gemfibrozil Area Under the Concentration vs. Time Curve (AUC)
Hide Description AUC (ng*hr/mL) of gemfibrozil when given as a 600 mg dose by itself compared to gemfibrozil AUC after 14.5 days of lopinavir-ritonavir (400mg/100mg) twice daily.
Time Frame 22 days per subject (approximately 1 year for entire study completion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Fifteen healthy volunteers were enrolled in this protocol based on an a priori power analysis. All 15 subjects completed the protocol and results reported are those from all 15 participants.
Arm/Group Title Gemfibrozil Alone (Control Group) Gemfibrozil + Lopinavir-ritonavir
Hide Arm/Group Description:
Subjects received a single 600 mg dose of gemfibrozil and serial blood samples were collected over a 24 hr. post-dose period to determine pharmacokinetic parameter values. Area under the concentrations vs. time curve from time zero to infinity (i.e. total drug exposure) was the primary pharmacokinetic parameter of interest. After completing participation in this control group, each subject "crossed over" to received lopinavir-ritonavir (400mg/100mg twice daily) for 14.5 days. Therefore, each subject served as their own control. Hence there were two groups of data analyzed, but each group consisted of the same subjects (tested under different conditions).
After receiving lopinavir-ritonavir (400mg/100mg twice daily) for 14.5 days, subjects received a single 600 mg dose of gemfibrozil and serial blood samples were collected over a 24 hr. post-dose period to determine pharmacokinetic parameter values. Area under the concentrations vs. time curve from time zero to infinity (i.e. total drug exposure) was the primary pharmacokinetic parameter of interest.
Overall Number of Participants Analyzed 15 15
Geometric Mean (90% Confidence Interval)
Unit of Measure: ng*hr/mL
104
(90 to 118)
62
(55 to 68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemfibrozil Alone (Control Group), Gemfibrozil + Lopinavir-ritonavir
Comments

Null hypothesis: lopinavir-ritonavir does not alter gemfibrozil pharmacokinetics.

A sample size of 13 healthy subjects yielded 81% power to detect a clinically relevant change of 30% in gemfibrozil AUC with concomitant lopinavir-ritonavir (alpha = 0.05; beta = 0.2). Gemfibrozil pharmacokinetic parameters derived pre- and post lopinavir-ritonavir exposure (Days 1 and 14, respectively) were compared using a paired Students t test.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments Students paired, two-tailed T-test
Time Frame Adverse event data were collected throughout the study. Each subject particpiated in this study for approximately 22 days, while the entire duration of the study (collectively) for all 15 subjects was approximately one year.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Gemfibrozil (GF) Alone Followed by GF + Lopinavir-ritonavir
Hide Arm/Group Description Subjects received a single 600 mg dose of gemfibrozil before- and after receiving lopinavir-ritonar 400mg/100mg twice daily, for 14.5 days. After each gemfibrozil dose, blood samples were collected for the determination of gemfibrozil plasma concentrations. The plasma concentrations were then used to determine gemfibrozil pharmacokinetic (PK) parameters values such as area under the concentration vs. time curve (AUC). PK Parameter values were then compared pre- and post lopinavir-ritonavir administration.
All-Cause Mortality
Gemfibrozil (GF) Alone Followed by GF + Lopinavir-ritonavir
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Gemfibrozil (GF) Alone Followed by GF + Lopinavir-ritonavir
Affected / at Risk (%)
Total   0/15 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Gemfibrozil (GF) Alone Followed by GF + Lopinavir-ritonavir
Affected / at Risk (%)
Total   0/15 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Scott Penzak
Organization: National Institutes of Health
Phone: 301-496-2997
Responsible Party: Scott Penzak, Pharm.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00474201     History of Changes
Other Study ID Numbers: 070149
07-CC-0149 CL006000-01 CC ( Other Identifier: Clinical Center Z number )
First Submitted: May 15, 2007
First Posted: May 16, 2007
Results First Submitted: March 23, 2010
Results First Posted: April 9, 2012
Last Update Posted: September 26, 2016