Safety and Pharmacokinetics of Clindamycin in Pediatric Subjects With BMI ≥ 85th Percentile - Full Text View

Purpose

The purpose of this study is better understand how clindamycin works in children who fall in the 85th percentile or higher for body mass index (a ratio of weight to height). The results of the study will help better understand if children in higher BMI ranges process the medication differently and whether dosing should be adjusted in these children.

Condition	Intervention	Phase
Bacterial Infections Obesity	Drug: Clindamycin	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Safety and Pharmacokinetics of Multiple-Dose Intravenous and Oral Clindamycin in Pediatric Subjects With BMI ≥ 85th Percentile (NICHD): CLIN01

Resource links provided by NLM:

MedlinePlus related topics: Bacterial Infections

Drug Information available for: Clindamycin Clindamycin hydrochloride Clindamycin phosphate Clindamycin palmitate hydrochloride Clindamycin palmitate

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Clearance (Cl) [ Time Frame: A population PK analysis will be done so multiple timeframes will be included (0 hr; 0.5 hr; 1-1.5 hr; 3-4 hr and 5-6 hr post-dose) ] [ Designated as safety issue: No ]
The PK schedule will be as follows:

Pre-dose 0 (within 15 minutes prior to the dose) 0.5 (± 5 minutes) 1-1.5 hrs 3-4 hrs 5-6 hrs
Volume of distribution (Vd) [ Time Frame: A population PK analysis will be done so multiple timeframes will be included (0 hr; 0.5 hr; 1-1.5 hr; 3-4 hr and 5-6 hr post-dose) ] [ Designated as safety issue: No ]
The PK schedule will be as follows:

Pre-dose 0 (within 15 minutes prior to the dose) 0.5 (± 5 minutes) 1-1.5 hrs 3-4 hrs 5-6 hrs
Area under the curve (AUCtau) [ Time Frame: A population PK analysis will be done so multiple timeframes will be included (0 hr; 0.5 hr; 1-1.5 hr; 3-4 hr and 5-6 hr post-dose) ] [ Designated as safety issue: No ]
The PK schedule will be as follows:

Pre-dose 0 (within 15 minutes prior to the dose) 0.5 (± 5 minutes) 1-1.5 hrs 3-4 hrs 5-6 hrs

Secondary Outcome Measures:

Oral apparent clearance (Cl/F) [ Time Frame: A population PK analysis will be done so multiple timeframes will be included (0 hr; 0.5 hr; 1-1.5 hr; 3-4 hr and 5-6 hr post-dose) ] [ Designated as safety issue: No ]
The PK schedule will be as follows:

Pre-dose 0 (within 15 minutes prior to the dose) 0.5 (± 5 minutes) 1-1.5 hrs 3-4 hrs 5-6 hrs
Oral apparent volume of distribution (V/F) [ Time Frame: A population PK analysis will be done so multiple timeframes will be included (0 hr; 0.5 hr; 1-1.5 hr; 3-4 hr and 5-6 hr post-dose) ] [ Designated as safety issue: No ]
The PK schedule will be as follows:

Pre-dose 0 (within 15 minutes prior to the dose) 0.5 (± 5 minutes) 1-1.5 hrs 3-4 hrs 5-6 hrs
Number of Adverse Events [ Time Frame: First dose of study medication to 3 days after last dose of study medication ] [ Designated as safety issue: Yes ]


Enrollment:	22
Study Start Date:	June 2013
Study Completion Date:	August 2014
Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Clindamycin Clindamycin phosphate (intravenous) Clindamycin hydrochloride (oral capsules) Clindamycin palmitate (oral solution) Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day will be allowed for children receiving clindamycin as part of clinical care.	Drug: Clindamycin Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day will be allowed for children receiving clindamycin as part of clinical care. Other Names: Clindamycin phosphate (intravenous) Clindamycin hydrochloride (oral capsules) Clindamycin palmitate (oral solution)

Detailed Description:

This is a prospective, open-label pharmacokinetic and safety study of multiple doses of IV and oral clindamycin in overweight and obese children 2 - < 18 years of age. The total study duration is expected to be approximately 24 months; each subject will participate in the study for up to 18 days (screening day; treatment days 1-14 [may be as short as 2 days] followed by an observation period of 3 days post discontinuation of clindamycin therapy or after day 17 (on day 18) of therapy in those who are treated with more than 14 days of clindamycin).

Eligibility


Ages Eligible for Study:	2 Years to 17 Years (Child)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

2 years - < 18 years of age at the time of first dose of study drug
Suspected or confirmed infection OR receiving IV clindamycin per routine care
Negative serum pregnancy test (if female and has reached menarche) within 24 hours of first dose of study drug and agreement to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy test through the last dose of study drug
BMI ≥ 85th percentile for age and sex, based on Centers for Disease Control (CDC) recommendations
Signed informed consent/Health Insurance Portability and Accountability Act (HIPAA) documents by the parent/legal guardian and assent (if applicable)

Exclusion Criteria:

The following apply only to those who are NOT already receiving clindamycin per routine care:
1. History of hypersensitivity or allergic reaction to clindamycin or lincomycin
2. History of C. difficile colitis with previous administration of clindamycin
3. Aspartate aminotransferase (AST) > 120 units/L
4. Alanine aminotransferase (ALT) > 210 units/L
5. Total bilirubin > 3 mg/dL
6. Serum creatinine > 2 mg/dL
7. Receiving a neuromuscular blocker as part of their therapy
Previous participation in the study
Subject is on prohibited medication or herbal product (see Appendix II)
Subject is receiving extracorporeal life support (ECLS)
Subject is post-cardiac bypass (within 24 hours)
Subject on inotropes/pressors
Any other condition or chronic illness that, in the opinion of the principal investigator, makes participation unadvised or unsafe

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01744730

Locations


United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Kansas
Children's Mercy Hospital
Kansas City, Kansas, United States, 64108
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 48109

Sponsors and Collaborators

Phillip Brian Smith

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators


Principal Investigator:	P. Brian Smith, MD, MHS, MPH	Duke Medical Center/Duke Clinical Research Institute
Principal Investigator:	Kevin Watt, MD	Duke Medical Center/Duke Clinical Research Institute
Principal Investigator:	Michael J Smith, MD	University of Louisville

More Information

Additional Information:

Pediatric Trials Network This link exits the ClinicalTrials.gov site

National Institute for Child Health and Human Development This link exits the ClinicalTrials.gov site


Responsible Party:	Phillip Brian Smith, Associate Professor of Pediatrics, Duke University Medical Center
ClinicalTrials.gov Identifier:	NCT01744730 History of Changes
Other Study ID Numbers:	Pro00041855 HHSN275201000003I
Study First Received:	December 5, 2012
Last Updated:	November 17, 2014
Health Authority:	United States: Food and Drug Administration United States: Data and Safety Monitoring Board United States: Institutional Review Board

Keywords provided by Duke University:


Bacterial infections Obesity pharmacokinetics clindamycin

Additional relevant MeSH terms:


Bacterial Infections Clindamycin Clindamycin palmitate Clindamycin phosphate Anti-Bacterial Agents	Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 27, 2016

Safety and Pharmacokinetics of Clindamycin in Pediatric Subjects With BMI ≥ 85th Percentile (CLIN01)