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A Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants (PTN_Acyclo)

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ClinicalTrials.gov Identifier: NCT00942084
Recruitment Status : Completed
First Posted : July 20, 2009
Results First Posted : January 8, 2014
Last Update Posted : January 8, 2014
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Phillip Brian Smith, Duke University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Herpes Simplex Virus
Neonatal Sepsis
Intervention Drug: Acyclovir
Enrollment 32

Recruitment Details Total enrollment is 32. 32 for safety analysis and 30 in PK population (28 included in final PK analysis).
Pre-assignment Details  
Arm/Group Title Acyclovir Study Enrollment
Hide Arm/Group Description Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Period Title: Overall Study
Started 32
Completed 30 [1]
Not Completed 2
Reason Not Completed
Death             2
[1]
There were 2 infant deaths. None determined to be related to study drug.
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Days
Postnatal Age (days) Number Analyzed 32 participants
3.0
(0.0 to 30.0)
Age, Continuous  
Median (Full Range)
Unit of measure:  Weeks
Gestational Age (weeks) Number Analyzed 32 participants
30.5
(23.0 to 40.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
17
  53.1%
Male
15
  46.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Hispanic or Latino
4
  12.5%
Not Hispanic or Latino
28
  87.5%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   3.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
11
  34.4%
White
20
  62.5%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 32 participants
32
Birthweight  
Median (Full Range)
Unit of measure:  Grams
Number Analyzed 32 participants
1295
(420 to 4840)
1.Primary Outcome
Title Clearance (CL)
Hide Description

Timeframe:

Version 1:0-5 min,2-4 hrs,6-8 hrs post doses 1 and 5-15; prior to doses 5-15 Version 2:0-15 min post doses 1 and 5-15; within 30 min prior to doses 2 and 5-15; 2-3 hrs post doses 5-15; 15-18 hrs post last dose

Time Frame V1:0-5 min,2-4 hrs,6-8 hrs post Doses 1&5-15;prior to doses 5-15; V2:0-15 min post doses 1&5-15; within 30 min prior to doses 2&5-15; 2-3 hrs post doses 5-15; 15-18 hrs post last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description:
Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: L/h/kg
0.278
(0.095 to 0.812)
2.Primary Outcome
Title Volume of Distribution (V)
Hide Description [Not Specified]
Time Frame up to 3 days of study drug administration and 10 days of safety monitoring
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description:
Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: L/kg
3.34
(0.293 to 10.85)
3.Primary Outcome
Title Half-life (T1/2)
Hide Description [Not Specified]
Time Frame up to 3 days of study drug administration and 10 days of safety monitoring
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description:
Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: h
7.07
(1.61 to 13.2)
4.Primary Outcome
Title Maximum Steady State Concentration (Cmaxss)
Hide Description [Not Specified]
Time Frame up to 3 dasy of study drug administration and 10 days of safety monitoring
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description:
Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: mg/L
11.1
(4.59 to 110)
5.Primary Outcome
Title Steady State Concentration at 50% of the Dosing Interval (C50ss)
Hide Description [Not Specified]
Time Frame up to 3 days of study drug administration and 10 days of safety monitoring
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description:
Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: mg/L
6.33
(3.38 to 65.7)
6.Primary Outcome
Title Minimum Steady State Concentration (Cminss)
Hide Description [Not Specified]
Time Frame up to 3 days of study drug administration and 10 days of safety monitoring
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description:
Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: mg/L
4.15
(2.19 to 39.3)
Time Frame Up to 3 days of study drug administration and 10 days of safety monitoring
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Acyclovir Study Design
Hide Arm/Group Description Two open-label PK studies contributed the data for this report. Version 1 was single-center and Version >=2 was multi-center. Acyclovir was administered intravenously as a 1-hour infusion for up to 3 days. Dosing in Study 1 was 500 mg/m2 every 8 hours. Dosing in Study 2 was determined by GA and PNA: 10 mg/kg every 12 hours (23-29 weeks GA and <14 days PNA); 20 mg/kg every 12 hours (23-29 weeks GA and 14-44 days PNA); and 20 mg/kg every 8 hours (30-34 weeks GA and <45 days PNA).
All-Cause Mortality
Acyclovir Study Design
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Acyclovir Study Design
Affected / at Risk (%) # Events
Total   4/32 (12.50%)    
General disorders   
Death  [1]  2/32 (6.25%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neuroblastoma   1/32 (3.13%)  1
Respiratory, thoracic and mediastinal disorders   
Neonatal asphyxia   1/32 (3.13%)  1
Indicates events were collected by systematic assessment
[1]
1 infant died due to nonketotic hyperglycinaemia and 1 infant dies due to sepsis.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Acyclovir Study Design
Affected / at Risk (%) # Events
Total   21/32 (65.63%)    
Blood and lymphatic system disorders   
Haemolytic anemia   1/32 (3.13%)  1
Cardiac disorders   
Cardiomegaly   1/32 (3.13%)  1
Congenital, familial and genetic disorders   
Atrial septal defect   1/32 (3.13%)  1
Congenital cardiovascular anomaly *  7/32 (21.88%)  7
Nonketotic hyperglycinaemia   1/32 (3.13%)  1
Patent ductus arteriosus   3/32 (9.38%)  3
Ventricular septal defect   1/32 (3.13%)  1
Endocrine disorders   
Adrenal insufficiency   3/32 (9.38%)  3
Hepatobiliary disorders   
Hyperbilirubinaemia   1/32 (3.13%)  1
Hyperbilirubinaemia neonatal   1/32 (3.13%)  1
Infections and infestations   
Sepsis   1/32 (3.13%)  1
Investigations   
Blood creatinine abnormal   1/32 (3.13%)  1
Blood creatinine increased   1/32 (3.13%)  1
Electrocardiogram QT prolonged   1/32 (3.13%)  1
Metabolism and nutrition disorders   
Electrolyte imbalance   1/32 (3.13%)  1
Hyperglycaemia   1/32 (3.13%)  1
Hyperkalaemia   1/32 (3.13%)  1
Hypoalbuminaemia   1/32 (3.13%)  1
Hypocalcaemia   1/32 (3.13%)  1
Neonatal hyponatraemia   1/32 (3.13%)  1
Nervous system disorders   
Intraventricular haemorrhage neonatal   1/32 (3.13%)  1
Renal and urinary disorders   
Renal failure   2/32 (6.25%)  2
Respiratory, thoracic and mediastinal disorders   
Apnoea   1/32 (3.13%)  1
Chronic respiratory disease   1/32 (3.13%)  1
Infantile apnoeic attack   2/32 (6.25%)  2
Pleural effusion   1/32 (3.13%)  1
Respiratory distress   1/32 (3.13%)  1
Skin and subcutaneous tissue disorders   
Dermatitis diaper  1/32 (3.13%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: P. Brian Smith, MD MPH MHS
Organization: Duke Clinical Research Institute
Phone: 919-668-8951
Other Publications:
Pickering LK. Red Book. 28th ed. Elk Grove Village, Illinois: American Academy of Pediatrics; 2009.
Responsible Party: Phillip Brian Smith, Duke University
ClinicalTrials.gov Identifier: NCT00942084     History of Changes
Other Study ID Numbers: Pro00028772
First Submitted: July 17, 2009
First Posted: July 20, 2009
Results First Submitted: August 27, 2013
Results First Posted: January 8, 2014
Last Update Posted: January 8, 2014