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

This study has been completed.
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Information provided by (Responsible Party):
Phillip Brian Smith, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01744730
First received: December 5, 2012
Last updated: November 21, 2016
Last verified: October 2016
  Purpose
The purpose of this study is to better understand how clindamycin works in children who fall in the 85th percentile or higher for body mass index (BMI - 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:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [ Time Frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6). ] [ Designated as safety issue: No ]

    In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis.

    PK sampling schedule for PTN_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of empirical Bayesian Estimates (EBE) for clearance by age cohort are presented below.

    Sampling schedule details for PTN_POPS and Staph Trio were comparable.


  • Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [ Time Frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples). ] [ Designated as safety issue: No ]

    In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis.

    PK sampling schedule for PTN_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for clearance by age cohort normalized to 1 kg of body weight are presented below.

    Sampling schedule details for PTN_POPS and Staph Trio were comparable.


  • Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [ Time Frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples). ] [ Designated as safety issue: No ]

    In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis.

    PK sampling schedule for PTN_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for clearance by age cohort normalized to 70 kg of body weight are presented below.

    Sampling schedule details for PTN_POPS and Staph Trio were comparable.


  • PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [ Time Frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples). ] [ Designated as safety issue: No ]

    In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis.

    PK sampling schedule for PTN_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for volume of distribution by age cohort are presented below.

    Sampling schedule details for PTN_POPS and Staph Trio were comparable.


  • PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [ Time Frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples). ] [ Designated as safety issue: No ]

    In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese & non-obese children: 1) PTN_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis.

    PK sampling schedule for PTN_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for volume of distribution by age cohort normalized to 1kg of body weight are presented below.

    Sampling schedule details for PTN_POPS & Staph Trio were comparable.



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 IV-ages 2 to 11 Years Old (BMI 85-95th Percentile)
Clindamycin IV: Children ages 2 to 11 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 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 was 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)
Active Comparator: Clindamycin IV-ages 2 to 11 Years Old (BMI Greater Than 95th)
Clindamycin IV: Children ages 2 to 11 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 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 was 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)
Active Comparator: Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile)
Clindamycin IV: Children ages 12 to 17 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 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 was 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)
Active Comparator: Clindamycin IV-ages 12 to 17 (BMI Greater Than 95th)
Clindamycin IV: Children ages 12 to 17 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 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 was 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 ages 2 to 17 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)
The EMMES Corporation
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:
Publications:

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
Results First Received: February 10, 2016
Last Updated: November 21, 2016
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 phosphate
Clindamycin
Clindamycin palmitate
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016