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

Sponsor
Phillip Brian Smith (Other)
Overall Status
Completed
CT.gov ID
NCT01744730
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), The Emmes Company, LLC (Industry)
22
Enrollment
4
Locations
4
Arms
14
Duration (Months)
5.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 1

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).

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (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
Study Start Date :
Jun 1, 2013
Actual Primary Completion Date :
Aug 1, 2014
Actual Study Completion Date :
Aug 1, 2014

Arms and Interventions

Arm Intervention/Treatment
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)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6).]

      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.

    2. Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).]

      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.

    3. Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).]

      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.

    4. PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).]

      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.

    5. PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. [After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Ann and Robert H. Lurie Children's Hospital of Chicago Chicago Illinois United States 60611
    2 Children's Mercy Hospital Kansas City Kansas United States 64108
    3 University of Louisville Louisville Kentucky United States 40202
    4 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 Company, LLC

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Phillip Brian Smith, Associate Professor of Pediatrics, Duke University
    ClinicalTrials.gov Identifier:
    NCT01744730
    Other Study ID Numbers:
    • Pro00041855
    • HHSN275201000003I
    First Posted:
    Dec 7, 2012
    Last Update Posted:
    Nov 29, 2016
    Last Verified:
    Oct 1, 2016
    Keywords provided by Phillip Brian Smith, Associate Professor of Pediatrics, Duke University
    Bacterial infections
    Obesity
    pharmacokinetics
    clindamycin
    Additional relevant MeSH terms:
    Bacterial Infections
    Clindamycin
    Clindamycin palmitate
    Clindamycin phosphate

    Study Results

    Participant Flow

    Recruitment Details Eligible participants (inpatients) were recruited in 4 hospitals in the United States. All participants were required to be receiving intravenous (IV) Clindamycin.
    Pre-assignment Detail Patients between the ages (and inclusive of these ages) of 2 years to 17 years at time of first dose of study medication were screened for all other inclusion and exclusion criteria which includes must have body mass index (BMI) greater than or equal to 85th percentile for age and sex, based on Centers for Disease Control (CDC) recommendations.
    Arm/Group Title Clindamycin IV-ages 2 to 11 Years Old (BMI 85-95th Percentile) Clindamycin IV-ages 2 to 11 Years Old (BMI Greater Than 95th) Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile) Clindamycin IV-ages 12 to 17 (BMI Greater Than 95th) Patients Less Than 21 Years of Age (NCT01431326)
    Arm/Group Description 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. 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. 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. 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. Standard of care clindamycin administration.
    Period Title: Overall Study
    STARTED 4 3 4 11 178
    COMPLETED 4 3 4 11 178
    NOT COMPLETED 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Clindamycin IV-ages 2 to 11 Years Old (BMI 85-95th Percentile) Clindamycin IV-ages 2 to 11 Years Old (BMI Greater Than 95th) Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile) Clindamycin IV-ages 12 to 17 (BMI Greater Than 95th) Patients Less Than 21 Years of Age (NCT01431326) Total
    Arm/Group Description 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. 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. 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. 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. Standard of care clindamycin administration Total of all reporting groups
    Overall Participants 4 3 4 11 178 200
    Age (Count of Participants)
    <=18 years
    4
    100%
    3
    100%
    4
    100%
    11
    100%
    178
    100%
    200
    100%
    Between 18 and 65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    9.4
    (2.7)
    10.6
    (1.4)
    14.6
    (1.7)
    14.8
    (1.7)
    7.2
    (6.9)
    7.8
    (6.8)
    Gender (Count of Participants)
    Female
    2
    50%
    0
    0%
    1
    25%
    1
    9.1%
    74
    41.6%
    78
    39%
    Male
    2
    50%
    3
    100%
    3
    75%
    10
    90.9%
    104
    58.4%
    122
    61%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    25%
    0
    0%
    0
    0%
    1
    9.1%
    52
    29.2%
    54
    27%
    Not Hispanic or Latino
    3
    75%
    2
    66.7%
    3
    75%
    10
    90.9%
    124
    69.7%
    142
    71%
    Unknown or Not Reported
    0
    0%
    1
    33.3%
    1
    25%
    0
    0%
    2
    1.1%
    4
    2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.1%
    2
    1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.6%
    1
    0.5%
    Black or African American
    0
    0%
    0
    0%
    1
    25%
    1
    9.1%
    28
    15.7%
    30
    15%
    White
    4
    100%
    2
    66.7%
    2
    50%
    10
    90.9%
    132
    74.2%
    150
    75%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.1%
    2
    1%
    Unknown or Not Reported
    0
    0%
    1
    33.3%
    1
    25%
    0
    0%
    13
    7.3%
    15
    7.5%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%
    3
    100%
    4
    100%
    11
    100%
    NA
    NaN
    NA
    NaN
    Body Mass Index (BMI) (Percentile) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Percentile]
    90.5
    (3.6)
    97.4
    (1.2)
    91.7
    (3.0)
    98.3
    (1.3)
    83.1
    (25.9)
    85.2
    (24.1)

    Outcome Measures

    1. Primary Outcome
    Title Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
    Description 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.
    Time Frame After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6).

    Outcome Measure Data

    Analysis Population Description
    In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN_Clinda obese study n = 21; PTN_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
    Arm/Group Title Clindamycin- Ages >2 to 6 Years Old (Non-Obese) Clindamycin- Ages >2 to 6 Years Old (Obese) Clindamycin- Ages >6 to 12 Years Old (Non-Obese) Clindamycin- Ages >6 to 12 Years Old (Obese) Clindamycin- Age >12 Years Old (Non-Obese) Clindamycin- Age >12 Years Old (Obese)
    Arm/Group Description Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile.
    Measure Participants 8 12 15 20 26 44
    Median (Full Range) [L/h]
    4.2
    5.7
    12.5
    10.7
    14.3
    19.2
    2. Primary Outcome
    Title Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
    Description 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.
    Time Frame After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).

    Outcome Measure Data

    Analysis Population Description
    In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN_Clinda obese study n = 21; PTN_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
    Arm/Group Title Clindamycin- Ages >2 to 6 Years Old (Non-Obese) Clindamycin- Ages >2 to 6 Years Old (Obese) Clindamycin- Ages >6 to 12 Years Old (Non-Obese) Clindamycin- Ages >6 to 12 Years Old (Obese) Clindamycin- Age >12 Years Old (Non-Obese) Clindamycin- Age >12 Years Old (Obese)
    Arm/Group Description Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile.
    Measure Participants 8 12 15 20 26 44
    Median (Full Range) [L/h/kg]
    0.2
    0.3
    0.3
    0.2
    0.2
    0.2
    3. Primary Outcome
    Title Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
    Description 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.
    Time Frame After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).

    Outcome Measure Data

    Analysis Population Description
    In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN_Clinda obese study n = 21; PTN_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
    Arm/Group Title Clindamycin- Ages >2 to 6 Years Old (Non-Obese) Clindamycin- Ages >2 to 6 Years Old (Obese) Clindamycin- Ages >6 to 12 Years Old (Non-Obese) Clindamycin- Ages >6 to 12 Years Old (Obese) Clindamycin- Age >12 Years Old (Non-Obese) Clindamycin- Age >12 Years Old (Obese)
    Arm/Group Description Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile.
    Measure Participants 8 12 15 20 26 44
    Median (Full Range) [L/h/70 kg]
    10.6
    14.8
    20.7
    14.7
    15.8
    14
    4. Primary Outcome
    Title PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
    Description 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.
    Time Frame After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).

    Outcome Measure Data

    Analysis Population Description
    In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN_Clinda obese study n = 21; PTN_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
    Arm/Group Title Clindamycin- Ages >2 to 6 Years Old (Non-Obese) Clindamycin- Ages >2 to 6 Years Old (Obese) Clindamycin- Ages >6 to 12 Years Old (Non-Obese) Clindamycin- Ages >6 to 12 Years Old (Obese) Clindamycin- Age >12 Years Old (Non-Obese) Clindamycin- Age >12 Years Old (Obese)
    Arm/Group Description Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile.
    Measure Participants 8 12 15 20 26 44
    Median (Full Range) [L]
    15.3
    17.6
    29.0
    46.9
    60.1
    85.8
    5. Post-Hoc Outcome
    Title Half-life
    Description 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 half-life by age cohort are presented below. Sampling schedule details for PTN_POPS and Staph Trio were comparable.
    Time Frame After participant transitioned from IV Clindamycin to oral Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).

    Outcome Measure Data

    Analysis Population Description
    In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN_Clinda obese study n = 21; PTN_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
    Arm/Group Title Clindamycin- Ages >2 to 6 Years Old (Non-Obese) Clindamycin- Ages >2 to 6 Years Old (Obese) Clindamycin- Ages >6 to 12 Years Old (Non-Obese) Clindamycin- Ages >6 to 12 Years Old (Obese) Clindamycin- Age >12 Years Old (Non-Obese) Clindamycin- Age >12 Years Old (Obese)
    Arm/Group Description Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile.
    Measure Participants 8 12 15 20 26 44
    Median (Full Range) [hours]
    2.4
    2.2
    2.2
    3.0
    2.8
    3.6
    6. Primary Outcome
    Title PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
    Description 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.
    Time Frame After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).

    Outcome Measure Data

    Analysis Population Description
    In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN_Clinda obese study n = 21; PTN_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
    Arm/Group Title Clindamycin- Ages >2 to 6 Years Old (Non-Obese) Clindamycin- Ages >2 to 6 Years Old (Obese) Clindamycin- Ages >6 to 12 Years Old (Non-Obese) Clindamycin- Ages >6 to 12 Years Old (Obese) Clindamycin- Age >12 Years Old (Non-Obese) Clindamycin- Age >12 Years Old (Obese)
    Arm/Group Description Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile. Non-obese patients were those with BMI <85th percentile. Obese patients were those with BMI greater to or equal to the 85th percentile.
    Measure Participants 8 12 15 20 26 44
    Median (Full Range) [L/kg]
    0.8
    0.9
    0.9
    1.0
    0.9
    0.9

    Adverse Events

    Time Frame Safety was assessed from the time of informed consent, up to 13 days after completion of the last study dose or early termination (approximately 30 days).
    Adverse Event Reporting Description
    Arm/Group Title Clindamycin IV-ages 2 to 11 (BMI 85- <95th Percentile) Clindamycin IV-ages 2 to 11 (BMI Greater Than or Equal 95th) Clinidamycin IV-ages 12 to 17 (BMI 85- <95th Percentile) Clindamycin IV-ages 12 to 17 (BMI Greater Than or Equal 95th) Patients Less Than 21 Years of Age (NCT01431326)
    Arm/Group Description 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. Clindamycin PO: Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 g/day. Dosing greater than 2.7 g/day was allowed for children receiving clindamycin as part of clinical care. Clindamycin IV: Children ages 2 to 11 years old with BMI greater than or equal 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. Clindamycin PO: Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 g/day. Dosing greater than 2.7 g/day was allowed for children receiving clindamycin as part of clinical care. 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. Clindamycin PO: Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 g/day. Dosing greater than 2.7 g/day was allowed for children receiving clindamycin as part of clinical care. Clindamycin IV: Children ages 12 to 17 years old with BMI greater than or equal 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. Clindamycin PO: Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 g/day. Dosing greater than 2.7 g/day was allowed for children receiving clindamycin as part of clinical care. Standard of care clindamycin administration
    All Cause Mortality
    Clindamycin IV-ages 2 to 11 (BMI 85- <95th Percentile) Clindamycin IV-ages 2 to 11 (BMI Greater Than or Equal 95th) Clinidamycin IV-ages 12 to 17 (BMI 85- <95th Percentile) Clindamycin IV-ages 12 to 17 (BMI Greater Than or Equal 95th) Patients Less Than 21 Years of Age (NCT01431326)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Clindamycin IV-ages 2 to 11 (BMI 85- <95th Percentile) Clindamycin IV-ages 2 to 11 (BMI Greater Than or Equal 95th) Clinidamycin IV-ages 12 to 17 (BMI 85- <95th Percentile) Clindamycin IV-ages 12 to 17 (BMI Greater Than or Equal 95th) Patients Less Than 21 Years of Age (NCT01431326)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/4 (25%) 0/3 (0%) 0/4 (0%) 0/11 (0%) 0/178 (0%)
    Respiratory, thoracic and mediastinal disorders
    Apnoea 1/4 (25%) 1 0/3 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/178 (0%) 0
    Other (Not Including Serious) Adverse Events
    Clindamycin IV-ages 2 to 11 (BMI 85- <95th Percentile) Clindamycin IV-ages 2 to 11 (BMI Greater Than or Equal 95th) Clinidamycin IV-ages 12 to 17 (BMI 85- <95th Percentile) Clindamycin IV-ages 12 to 17 (BMI Greater Than or Equal 95th) Patients Less Than 21 Years of Age (NCT01431326)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/3 (0%) 0/4 (0%) 2/11 (18.2%) 0/178 (0%)
    Skin and subcutaneous tissue disorders
    Rash 0/4 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/178 (0%) 1
    Vascular disorders
    Jugular vein thrombosis 0/4 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/178 (0%) 1

    Limitations/Caveats

    Data from 3 different studies was included to increase the robustness of the population PK model developed and leverage all available clindamycin PK data.

    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 Kevin Watt, MD
    Organization Duke Clinical Research Institute, Duke University School of Medicine
    Phone 919-668-8556
    Email kevin.watt@dm.duke.edu
    Responsible Party:
    Phillip Brian Smith, Associate Professor of Pediatrics, Duke University
    ClinicalTrials.gov Identifier:
    NCT01744730
    Other Study ID Numbers:
    • Pro00041855
    • HHSN275201000003I
    First Posted:
    Dec 7, 2012
    Last Update Posted:
    Nov 29, 2016
    Last Verified:
    Oct 1, 2016