Lopinavir/Ritonavir (Kaletra) PK in Children

• ClinicalTrials.gov Identifier: NCT00810108
• Recruitment Status: Completed
• First Posted: December 17, 2008
• Results First Posted: July 6, 2012
• Last Update Posted: July 6, 2012
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Collaborator: American Association of Colleges of Pharmacy
• Information provided by (Responsible Party): Brookie Best, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: HIV/AIDS Treatment; HIV Infections
• Intervention: Drug: lopinavir/ritonavir (Kaletra®) tablets
• Enrollment: 12

Participant Flow

Recruitment Details	Subjects were recruited between August 2008 to August 2009 from the Special Immunology Program at Children' National Medical Center in Washington DC.
Pre-assignment Details

Arm/Group Title	Whole Then Crushed Tablets	Crushed Then Whole Tablets
Arm/Group Description	These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.	These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.
Period Title: Overall Study
Started	6	7
Completed	5	7
Not Completed	1	0
Reason Not Completed
Withdrawal by Subject	1	0

Baseline Characteristics

Arm/Group Title		Whole Then Crushed Tablets	Crushed Then Whole Tablets	Total
Arm/Group Description		These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.	These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.	Total of all reporting groups
Overall Number of Baseline Participants		6	7	13
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	7 participants	13 participants
	<=18 years	6 100.0%	7 100.0%	13 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	6 participants	7 participants	13 participants
		12; (10 to 16)	13; (12 to 16)	13; (10 to 16)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	7 participants	13 participants
	Female	3 50.0%	4 57.1%	7 53.8%
	Male	3 50.0%	3 42.9%	6 46.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	6 participants	7 participants	13 participants
		6	7	13

Outcome Measures

1. Primary Outcome

Title	Lopinavir Area Under the Curve (AUC)
Description	Lopinavir Area Under the Plasma Concentration versus Time Curve (AUC)
Time Frame	pre-dose, 1,2,4,6,8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

All subjects who completed the pharmacokinetic sampling visits with whole tablet administration were analyzed

Arm/Group Title	All Subjects Taking Whole Tablets	All Subjects Taking Crushed Tablets
Arm/Group Description:	Lopinavir AUC from all subjects taking the whole tablet	Lopinavir AUC from all subjects taking the crushed tablet
Overall Number of Participants Analyzed	12	12
Median (Inter-Quartile Range); Unit of Measure: mg*hr/L
	144; (101 to 202)	92; (79 to 103)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Subjects Taking Whole Tablets, All Subjects Taking Crushed Tablets
	Comments	Lopinavir AUC was compared between whole tablet and crushed tablet administration by using a ratio of crushed/whole AUC.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The geometric mean and 90% confidence interval assessed whether the crushed and whole tablet administration AUCs were equivalent.
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of Crushed/Whole Tablet AUC
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 90%; 0.45 to 0.69
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	All Subjects
Arm/Group Description	Data from all subjects combined
All-Cause Mortality
	All Subjects
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	All Subjects
	Affected / at Risk (%)
Total	0/13 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	All Subjects
	Affected / at Risk (%)
Total	0/13 (0.00%)

Limitations and Caveats

The AUC of the crushed tablet administration were measured after a single dose only, rather than at steady-state; variable adherence may have impacted results.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Brookie M. Best, Associate Professor
• Organization: University of California San Diego
• Phone: 858-822-5550
• EMail: brookie@ucsd.edu

• Responsible Party: Brookie Best, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• ClinicalTrials.gov Identifier: NCT00810108
• Other Study ID Numbers: 10894
• First Submitted: December 15, 2008
• First Posted: December 17, 2008
• Results First Submitted: April 25, 2012
• Results First Posted: July 6, 2012
• Last Update Posted: July 6, 2012