Clinical Trial Results:
A Phase I, Open-Label, Single-Dose Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Dalbavancin In Hospitalized Children Of Age 3 Months To 11 Years Receiving Standard Intravenous Anti-Infective Treatment For Bacterial Infections
Summary
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EudraCT number |
2013-003227-11 |
Trial protocol |
EE |
Global end of trial date |
16 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Aug 2018
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First version publication date |
22 Aug 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DUR001-106
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01946568 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Allergan Pharmaceutical International Ltd
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Sponsor organisation address |
Clonshaugh Business & Technology Park, Coolock, Dublin, Ireland, D17 E400
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Public contact |
Clinical Trials Registry Team, Allergan plc, 001 877‐277‐8566, IR-CTRegistration@Allergan.com
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Scientific contact |
Therapeutic Area Head, Allergan plc, 001 862-261-7000, IR-CTRegistration@Allergan.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000016-PIP01-07 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Apr 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Apr 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this clinical trial was to characterize the pharmacokinetics of dalbavancin in pediatric participants of age 3 months to 11 years (inclusive) following the intravenous administration of a single dose of dalbavancin.
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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Aug 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 36
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Worldwide total number of subjects |
36
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
12
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Children (2-11 years) |
24
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
Participants were treated and results were evaluated in 3 age cohorts as follows: Cohort 1: Age 6 to 11 years, inclusive Cohort 2: Age 2 to <6 years Cohort 3: Age 3 months to <2 years. To have at least 10 participants in each cohort, approximately 12 participants per cohort were planned to be enrolled. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 3: 3 Months to <2 Years | ||||||||||||||||||||||||
Arm description |
Participants of age 3 months to <2 years received dalbavancin at a dose of 10 mg/kg as a 30-minute intravenous (IV) infusion. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Dalbavancin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Intravenous dalbavancin was administered at a dose of 10 mg/kg as a 30-minute IV infusion to participants to participants 3 months to <2 years of age.
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Arm title
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Cohort 2: 2 to 6 Years | ||||||||||||||||||||||||
Arm description |
Participants of age 2 years to <6 years received dalbavancin at a dose of 15-25 mg/kg as a 30-minute IV infusion. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Dalbavancin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Intravenous dalbavancin was administered at a dose of 15-25 mg/kg as a 30-minute IV infusion to participants between 2 to 6 years of age.
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Arm title
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Cohort 1: 6 to 11 Years | ||||||||||||||||||||||||
Arm description |
Participants of age 6 years to 11 years, inclusive received dalbavancin at a dose of 15 mg/kg as a 30-minute IV infusion. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Dalbavancin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Intravenous dalbavancin was administered at a dose of 15 mg/kg as a 30-minute IV infusion (not to exceed 1000 mg) to participants between 6 to 11 years of age.
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Baseline characteristics reporting groups
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Reporting group title |
Cohort 3: 3 Months to <2 Years
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Reporting group description |
Participants of age 3 months to <2 years received dalbavancin at a dose of 10 mg/kg as a 30-minute intravenous (IV) infusion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2: 2 to 6 Years
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Reporting group description |
Participants of age 2 years to <6 years received dalbavancin at a dose of 15-25 mg/kg as a 30-minute IV infusion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 1: 6 to 11 Years
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Reporting group description |
Participants of age 6 years to 11 years, inclusive received dalbavancin at a dose of 15 mg/kg as a 30-minute IV infusion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort 3: 3 Months to <2 Years
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Reporting group description |
Participants of age 3 months to <2 years received dalbavancin at a dose of 10 mg/kg as a 30-minute intravenous (IV) infusion. | ||
Reporting group title |
Cohort 2: 2 to 6 Years
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Reporting group description |
Participants of age 2 years to <6 years received dalbavancin at a dose of 15-25 mg/kg as a 30-minute IV infusion. | ||
Reporting group title |
Cohort 1: 6 to 11 Years
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Reporting group description |
Participants of age 6 years to 11 years, inclusive received dalbavancin at a dose of 15 mg/kg as a 30-minute IV infusion. |
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End point title |
Area Under The Plasma Concentration-Time Curve From Zero To Infinity (AUC0–Inf) of Dalbavancin [1] | ||||||||||||||||
End point description |
Area under the concentration-time curve of the dalbavancin in plasma over the time interval from 0 extrapolated to infinity based on the population pharmacokinetic model. AUC0-inf was calculated as Dose (mg) divided by clearance (CL) in L/hr. AUC is expressed as microgram hours per milliliter (µg*hr/mL). The Pharmacokinetic analysis population comprised all treated participants who had at least 1 evaluable pharmacokinetic sample.
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End point type |
Primary
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End point timeframe |
Based on plasma concentrations at 0.5 hours, 4 hours, 12 hours, 24 hours, 144 hours and 648 hours post-dose
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary objective of this study is to evaluate the safety and tolerability of dalbavancin in children and it is not powered for inferential statistical analysis. |
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No statistical analyses for this end point |
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End point title |
Maximum Observed Plasma Concentration (Cmax) of Dalbavancin [2] | ||||||||||||||||
End point description |
Maximum measured concentration of the dalbavancin in plasma based on the population pharmacokinetic model. Concentration is expressed as microgram per milliliter (µg/mL). The Pharmacokinetic analysis population comprised all treated participants who had at least 1 evaluable pharmacokinetic sample.
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End point type |
Primary
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End point timeframe |
Based on plasma concentrations at 0.5 hours, 4 hours, 12 hours, 24 hours,144 hours and 648 hours post-dose
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary objective of this study is to evaluate the safety and tolerability of dalbavancin in children and it is not powered for inferential statistical analysis. |
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No statistical analyses for this end point |
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End point title |
Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours Post-dose (AUC0-120) for Dalbavancin [3] | ||||||||||||||||
End point description |
Area under the concentration-time curve of the dalbavancin in plasma over the time interval from 0 up to 120 hours based on the population pharmacokinetic model. AUC is expressed as microgram hours per milliliter (µg*hr/mL). The Pharmacokinetic analysis population comprised all treated participants who had at least 1 evaluable pharmacokinetic sample.
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End point type |
Primary
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End point timeframe |
Based on plasma concentrations at 0.5 hours, 4 hours, 12 hours, 24 hours,144 hours and 648 hours post-dose
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary objective of this study is to evaluate the safety and tolerability of dalbavancin in children and it is not powered for inferential statistical analysis. |
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No statistical analyses for this end point |
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End point title |
Area Under the Plasma Concentration-Time Curve From Time 0 to 648 Hours Post-dose (AUC0-648) for Dalbavancin [4] | ||||||||||||||||
End point description |
Area under the concentration-time curve of the dalbavancin in plasma from 0 to last measurable concentration. AUC is expressed as microgram hours per milliliter (µg*hr/mL). The Pharmacokinetic analysis population comprised all treated participants who had at least 1 evaluable pharmacokinetic sample.
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End point type |
Primary
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End point timeframe |
Based on plasma concentrations at 0.5 hours, 4 hours, 12 hours, 24 hours,144 hours and 648 hours post-dose
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary objective of this study is to evaluate the safety and tolerability of dalbavancin in children and it is not powered for inferential statistical analysis. |
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No statistical analyses for this end point |
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End point title |
Time to Maximum Observed Plasma Concentration [5] | ||||||||||||||||
End point description |
Time to Maximum Serum Concentration (Tmax) of dalbavancin based on the population pharmaokinetic model. The Pharmacokinetic analysis population comprised all treated participants who had at least 1 evaluable pharmacokinetic sample.
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End point type |
Primary
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End point timeframe |
Based on plasma concentrations at 0.5 hours, 4 hours, 12 hours, 24 hours,144 hours and 648 hours post-dose
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary objective of this study is to evaluate the safety and tolerability of dalbavancin in children and it is not powered for inferential statistical analysis. |
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No statistical analyses for this end point |
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End point title |
Terminal Phase Elimination Half-life (T1/2) for Dalbavancin [6] | ||||||||||||||||
End point description |
T1/2 of dalbavancin was derived based on population pharmacokinetic model-derived individual post hoc pharmacokinetic parameters. The Pharmacokinetic analysis population comprised all treated participants who had at least 1 evaluable pharmacokinetic sample.
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End point type |
Primary
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End point timeframe |
Based on plasma concentrations at 0.5 hours, 4 hours, 12 hours, 24 hours,144 hours and 648 hours post-dose
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Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary objective of this study is to evaluate the safety and tolerability of dalbavancin in children and it is not powered for inferential statistical analysis. |
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No statistical analyses for this end point |
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End point title |
Number of Participants with Treatment-emergent Adverse Events | ||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event need not necessarily have a causal relationship with the treatment or usage. An AE is considered treatment emergent if the AE starts during or after study drug administration through the last follow-up visit (Day 28). The safety population consists of participants enrolled in the study who have received any amount of the study drug.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With Abnormal Hematology and Chemistry Laboratory Values | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The percentage of participants with abnormal hematology and chemistry laboratory values that occurred in more than 1 participant are reported. Here, Laboratory abnormalities were assessed using local laboratory criteria in which ULN indicates Upper Limit of Normal and LLN is Lower Limit of Normal. The safety population consists of participants enrolled in the study who have received any amount of the study drug and were evaluable for laboratory abnormality.
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End point type |
Secondary
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End point timeframe |
Up to Day 7
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Change in Vital Signs | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Vital signs included supine blood pressure and pulse rate. Categorical summaries of vital signs data were reported as absolute vital signs, increases in vital signs, and decreases in vital signs. For 3 months to <2 years of age group, criteria for supine systolic BP was <80 mmHg, supine diastolic BP was <55, supine pulse rate was <80 to >120 mmHg. For 2 to <6 years of age group, criteria for supine systolic BP was <95 mmHg, supine diastolic BP was <60, supine pulse rate was <65 to >110 mmHg. For 6 to 11 years of age group, criteria for supine systolic BP was <100 mmHg, supine diastolic BP was <60, supine pulse rate was <60 to >95 mmHg. The criteria for reporting increase and decrease in supine systolic BP was >=30 and supine diastolic BP was >=20 mmHg for all age groups. The safety population consists of participants enrolled in the study who have received any amount of the study drug.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 28 days
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Adverse event reporting additional description |
The safety population consists of participants enrolled in the study who have received any amount of the study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Cohort 3: 3 Months to <2 Years
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Reporting group description |
Participants of age 3 months to <2 years received dalbavancin at a dose of 10 mg/kg as a 30-minute intravenous (IV) infusion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 1: 6 to 11 Years
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Reporting group description |
Participants of age 6 years to 11 years, inclusive received dalbavancin at a dose of 15 mg/kg as a 30-minute IV infusion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2: 2 to 6 Years
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Reporting group description |
Participants of age 2 years to <6 years received dalbavancin at a dose of 15-25 mg/kg as a 30-minute IV infusion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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07 Nov 2013 |
1. 5 participants were enrolled under version 1 of protocol dated 11-April-2013. 2. No participants were enrolled under version 2.1 dated 07-November-2013. 3. Study Design was changed from all participants to be enrolled in parallel to participants in cohort 1 and 2 to be enrolled in parallel, and participants in cohort 3 to be enrolled after safety data from the other 2 cohorts had been reviewed and shared with the FDA to reflect communications from FDA requesting that enrollment in cohort 3 begin after safety data from the older cohorts were reviewed and shared with FDA. 4. Other assessments and analyses stated that interim analysis of PK and safety would be performed in approximately the first 6 evaluable participants. 5. The wording of criterion#1 was clarified in inclusion criteria which reflects that participants with urinary tract infection could be enrolled. 6. Inclusion Criterion#5 was changed to remove “normal” from the audiologic assessment and to change the time within which the audiologic assessment had to be performed from with 3 days before study drug administration to within 7 days before in order to clarify that participant may be enrolled during the 7 days before the first dose of study drug, regardless of the results of audiology assessments. This change reflects the lack of association between dalbavancin treatment and ototoxicity, but audiology assessments would continue to be performed due to previous regulatory commitment. 7. “Half-lives”, treatment with an investigational drug within 30 days or 5 half-lives, whichever was longer, were removed from exclusion criterion#1 to make it more clinically relevant. |
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07 Nov 2013 |
8. Exclusion Criteria#2, History of fluctuant hearing; persistent tinnitus; balance disorder; otologic surgery or disease; tumor of the head, neck, or auditory system; head injury; Meniere’s disease; autoimmune inner ear disease; perilymphatic fistula; CNS disorder resulting in hearing deficits; or significant noise exposure was removed because audiology assessments would provide necessary data regarding baseline and follow-up hearing for each participant. 9. Exclusion Criteria#3 significant exposure (greater than one week duration of therapy) to aminoglycoside antibiotics or chemotherapy currently or within a week prior to enrollment into the study or current use of loop diuretics was removed because there is no known drug interaction between dalbavancin and the drugs listed. Additionally, audiology assessments would provide necessary data regarding baseline and follow-up hearing for each participant. 10. Exclusion Criteria#4 was modified to clarify that participants currently receiving IV vancomycin should be excluded. The safety of dalbavancin co-administered with other glycopeptides has not been established. However, given the short half-life of vancomycin, and the likely subtherapeutic concentration of vancomycin in children, prior use of intravenous vancomycin should not prohibit the administration of dalbavancin, as long as dalbavancin is administered at least 8 hours after the last dose of vancomycin. 11. Exclusion Criteria#6, “or physical exam evidence of malnutrition” was removed to make it more clinically relevant. 12. New text, “Patients enrolled with an abnormal baseline audiology exam may be replaced if needed” was added to Overall Study Design and Plan to ensure enough evaluable participants were available for analysis. |
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07 Nov 2013 |
13. Table 1 was removed from Treatment Administration and “Reconstituted dalbavancin must be further diluted by addition of 5% Dextrose for Injection, USP and mixed gently (see the Pharmacy Manual)” was added. 14. In Packing and Labeling “by addition to a 250 ml infusion bag of 5% Dextrose Injection, USP” was deleted. 15. In Pharmacokinetic Sampling, proper collection of PK samples was clarified and allowed for collection of extra PK sample if needed. 16. 19 participants were enrolled under version 2.2, also dated 07-November-2013. This amendment was due to a corporate name change, from Durata Therapeutics, Inc. to Durata Therapeutics International B.V. |
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12 Sep 2014 |
1. 12 participants were enrolled under version 3.0. 2. Study Design was changed to add ± 2 minutes to the 30-minute dalbavancin infusion in order to maintain consistency with Pharmacy Manual. 3. Dalbavancin dose was adjusted to 10 mg/kg for participants in Cohort 3 in the study design as based on interim PK analysis, it was inferred that dose of 10 mg/kg in participants 3 months to < 2 years of age expected to provide dalbavancin exposure similar to that previously observed in clinical studies with adults. 4. Results of interim PK analysis were added in study design to support revision to dalbavancin dosing for remaining participants. 5. An exclusion criterion was added for participants diagnosed with cystic fibrosis as PK and audiology rest results more variable in cystic fibrosis participants than in other children. 6. Approximate duration of study was changed from 1.0 years, ending in June 2014, to 2.0 years, ending in October 2015 to reflect recruitment. 7. Storage time was changed for both reconstituted and diluted dalbavancin from 24 hours to 48 hours in Storage and Accountability section to maintain consistency with approved product information for dalbavancin. 8. The language was simplified regarding audiologic testing. 9. Window of ±5 minutes was added to PK sampling within 30 minutes of dalbavancin IV infusion to maintain consistency with windows for other PK sample collections. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |