Trial Outcomes & Findings for Safety and Pharmacokinetics of Clindamycin in Pediatric Subjects With BMI ≥ 85th Percentile (NCT NCT01744730)
NCT ID: NCT01744730
Last Updated: 2016-11-29
Results Overview
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.
COMPLETED
PHASE1
22 participants
After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6).
2016-11-29
Participant Flow
Eligible participants (inpatients) were recruited in 4 hospitals in the United States. All participants were required to be receiving intravenous (IV) Clindamycin.
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
Patients Less Than 21 Years of Age (NCT01431326)
Standard of care clindamycin administration.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
4
|
11
|
178
|
|
Overall Study
COMPLETED
|
4
|
3
|
4
|
11
|
178
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Pharmacokinetics of Clindamycin in Pediatric Subjects With BMI ≥ 85th Percentile
Baseline characteristics by cohort
| Measure |
Clindamycin IV-ages 2 to 11 Years Old (BMI 85-95th Percentile)
n=4 Participants
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-ages 2 to 11 Years Old (BMI Greater Than 95th)
n=3 Participants
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.
|
Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile)
n=4 Participants
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-ages 12 to 17 (BMI Greater Than 95th)
n=11 Participants
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.
|
Patients Less Than 21 Years of Age (NCT01431326)
n=178 Participants
Standard of care clindamycin administration
|
Total
n=200 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
178 Participants
n=21 Participants
|
200 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Age, Continuous
|
9.4 years
STANDARD_DEVIATION 2.7 • n=5 Participants
|
10.6 years
STANDARD_DEVIATION 1.4 • n=7 Participants
|
14.6 years
STANDARD_DEVIATION 1.7 • n=5 Participants
|
14.8 years
STANDARD_DEVIATION 1.7 • n=4 Participants
|
7.2 years
STANDARD_DEVIATION 6.9 • n=21 Participants
|
7.8 years
STANDARD_DEVIATION 6.8 • n=8 Participants
|
|
Gender
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
74 Participants
n=21 Participants
|
78 Participants
n=8 Participants
|
|
Gender
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
104 Participants
n=21 Participants
|
122 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
52 Participants
n=21 Participants
|
54 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
124 Participants
n=21 Participants
|
142 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
30 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
132 Participants
n=21 Participants
|
150 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
15 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
11 participants
n=4 Participants
|
NA participants
n=21 Participants
|
NA participants
n=8 Participants
|
|
Body Mass Index (BMI)
|
90.5 Percentile
STANDARD_DEVIATION 3.6 • n=5 Participants
|
97.4 Percentile
STANDARD_DEVIATION 1.2 • n=7 Participants
|
91.7 Percentile
STANDARD_DEVIATION 3.0 • n=5 Participants
|
98.3 Percentile
STANDARD_DEVIATION 1.3 • n=4 Participants
|
83.1 Percentile
STANDARD_DEVIATION 25.9 • n=21 Participants
|
85.2 Percentile
STANDARD_DEVIATION 24.1 • n=8 Participants
|
PRIMARY outcome
Timeframe: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6).Population: 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.
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.
Outcome measures
| Measure |
Clindamycin- Ages >2 to 6 Years Old (Non-Obese)
n=8 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >2 to 6 Years Old (Obese)
n=12 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Non-Obese)
n=15 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Obese)
n=20 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Age >12 Years Old (Non-Obese)
n=26 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Age >12 Years Old (Obese)
n=44 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
|
4.2 L/h
Interval 0.9 to 9.1
|
5.7 L/h
Interval 1.8 to 8.3
|
12.5 L/h
Interval 3.6 to 34.4
|
10.7 L/h
Interval 4.7 to 26.7
|
14.3 L/h
Interval 5.6 to 37.4
|
19.2 L/h
Interval 3.9 to 33.7
|
PRIMARY outcome
Timeframe: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).Population: 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.
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.
Outcome measures
| Measure |
Clindamycin- Ages >2 to 6 Years Old (Non-Obese)
n=8 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >2 to 6 Years Old (Obese)
n=12 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Non-Obese)
n=15 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Obese)
n=20 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Age >12 Years Old (Non-Obese)
n=26 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Age >12 Years Old (Obese)
n=44 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
|
0.2 L/h/kg
Interval 0.1 to 0.8
|
0.3 L/h/kg
Interval 0.1 to 0.4
|
0.3 L/h/kg
Interval 0.1 to 0.8
|
0.2 L/h/kg
Interval 0.1 to 0.6
|
0.2 L/h/kg
Interval 0.1 to 0.5
|
0.2 L/h/kg
Interval 0.0 to 0.7
|
PRIMARY outcome
Timeframe: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).Population: 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.
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.
Outcome measures
| Measure |
Clindamycin- Ages >2 to 6 Years Old (Non-Obese)
n=8 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >2 to 6 Years Old (Obese)
n=12 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Non-Obese)
n=15 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Obese)
n=20 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Age >12 Years Old (Non-Obese)
n=26 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Age >12 Years Old (Obese)
n=44 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
|
10.6 L/h/70 kg
Interval 3.6 to 35.0
|
14.8 L/h/70 kg
Interval 5.5 to 20.3
|
20.7 L/h/70 kg
Interval 7.1 to 48.5
|
14.7 L/h/70 kg
Interval 5.9 to 39.2
|
15.8 L/h/70 kg
Interval 4.7 to 34.7
|
14 L/h/70 kg
Interval 3.1 to 37.9
|
PRIMARY outcome
Timeframe: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).Population: 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.
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.
Outcome measures
| Measure |
Clindamycin- Ages >2 to 6 Years Old (Non-Obese)
n=8 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >2 to 6 Years Old (Obese)
n=12 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Non-Obese)
n=15 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Obese)
n=20 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Age >12 Years Old (Non-Obese)
n=26 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Age >12 Years Old (Obese)
n=44 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
|---|---|---|---|---|---|---|
|
PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
|
15.3 L
Interval 7.6 to 19.7
|
17.6 L
Interval 8.4 to 25.2
|
29.0 L
Interval 17.5 to 57.4
|
46.9 L
Interval 32.9 to 85.8
|
60.1 L
Interval 22.5 to 94.6
|
85.8 L
Interval 28.5 to 160.0
|
PRIMARY outcome
Timeframe: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).Population: 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.
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.
Outcome measures
| Measure |
Clindamycin- Ages >2 to 6 Years Old (Non-Obese)
n=8 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >2 to 6 Years Old (Obese)
n=12 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Non-Obese)
n=15 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Obese)
n=20 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Age >12 Years Old (Non-Obese)
n=26 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Age >12 Years Old (Obese)
n=44 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
|---|---|---|---|---|---|---|
|
PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
|
0.8 L/kg
Interval 0.7 to 1.3
|
0.9 L/kg
Interval 0.7 to 1.0
|
0.9 L/kg
Interval 0.7 to 1.1
|
1.0 L/kg
Interval 0.7 to 1.3
|
0.9 L/kg
Interval 0.7 to 1.3
|
0.9 L/kg
Interval 0.6 to 1.6
|
POST_HOC outcome
Timeframe: After participant transitioned from IV Clindamycin to oral Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).Population: 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.
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.
Outcome measures
| Measure |
Clindamycin- Ages >2 to 6 Years Old (Non-Obese)
n=8 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >2 to 6 Years Old (Obese)
n=12 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Non-Obese)
n=15 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Ages >6 to 12 Years Old (Obese)
n=20 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
Clindamycin- Age >12 Years Old (Non-Obese)
n=26 Participants
Non-obese patients were those with BMI \<85th percentile.
|
Clindamycin- Age >12 Years Old (Obese)
n=44 Participants
Obese patients were those with BMI greater to or equal to the 85th percentile.
|
|---|---|---|---|---|---|---|
|
Half-life
|
2.4 hours
Interval 1.1 to 5.9
|
2.2 hours
Interval 1.5 to 4.4
|
2.2 hours
Interval 0.9 to 5.8
|
3.0 hours
Interval 1.2 to 6.3
|
2.8 hours
Interval 1.2 to 7.6
|
3.6 hours
Interval 0.9 to 11.3
|
Adverse Events
Clindamycin IV-ages 12 to 17 (BMI Greater Than or Equal 95th)
Patients Less Than 21 Years of Age (NCT01431326)
Clinidamycin IV-ages 12 to 17 (BMI 85- <95th Percentile)
Clindamycin IV-ages 2 to 11 (BMI 85- <95th Percentile)
Clindamycin IV-ages 2 to 11 (BMI Greater Than or Equal 95th)
Serious adverse events
| Measure |
Clindamycin IV-ages 12 to 17 (BMI Greater Than or Equal 95th)
n=11 participants at risk
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.
|
Patients Less Than 21 Years of Age (NCT01431326)
n=178 participants at risk
Standard of care clindamycin administration
|
Clinidamycin IV-ages 12 to 17 (BMI 85- <95th Percentile)
n=4 participants at risk
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-ages 2 to 11 (BMI 85- <95th Percentile)
n=4 participants at risk
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-ages 2 to 11 (BMI Greater Than or Equal 95th)
n=3 participants at risk
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.
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
0.00%
0/11 • 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).
|
0.00%
0/178 • 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).
|
0.00%
0/4 • 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).
|
25.0%
1/4 • Number of events 1 • 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).
|
0.00%
0/3 • 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).
|
Other adverse events
| Measure |
Clindamycin IV-ages 12 to 17 (BMI Greater Than or Equal 95th)
n=11 participants at risk
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.
|
Patients Less Than 21 Years of Age (NCT01431326)
n=178 participants at risk
Standard of care clindamycin administration
|
Clinidamycin IV-ages 12 to 17 (BMI 85- <95th Percentile)
n=4 participants at risk
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-ages 2 to 11 (BMI 85- <95th Percentile)
n=4 participants at risk
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-ages 2 to 11 (BMI Greater Than or Equal 95th)
n=3 participants at risk
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.
|
|---|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
9.1%
1/11 • Number of events 1 • 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).
|
0.00%
0/178 • 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).
|
0.00%
0/4 • 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).
|
0.00%
0/4 • 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).
|
0.00%
0/3 • 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).
|
|
Vascular disorders
Jugular vein thrombosis
|
9.1%
1/11 • Number of events 1 • 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).
|
0.00%
0/178 • 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).
|
0.00%
0/4 • 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).
|
0.00%
0/4 • 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).
|
0.00%
0/3 • 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).
|
Additional Information
Kevin Watt, MD
Duke Clinical Research Institute, Duke University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place