Trial Outcomes & Findings for A Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants (PTN_Acyclo) (NCT NCT00942084)

NCT ID: NCT00942084

Last Updated: 2019-01-08

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 32 participants
• Primary outcome timeframe: 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
• Results posted on: 2019-01-08

Participant Flow

Total enrollment is 32. 32 for safety analysis and 30 in PK population (28 included in final PK analysis).

Participant milestones

Measure	Acyclovir Study Enrollment 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 Study STARTED	32
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure

Acyclovir Study Enrollment 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 Study Death

2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Acyclovir Study Design n=32 Participants 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).
Age, Continuous Postnatal Age (days)	3.0 days n=5 Participants
Age, Continuous Gestational Age (weeks)	30.5 weeks n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants
Birthweight	1295 grams n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: 32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.

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

Outcome measures

Measure

Acyclovir Study Design n=28 Participants 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).

Clearance (CL)

0.278 L/h/kg Interval 0.095 to 0.812

PRIMARY outcome

Timeframe: up to 3 days of study drug administration and 10 days of safety monitoring

Population: 32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.

Outcome measures

Measure

Acyclovir Study Design n=28 Participants 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).

Volume of Distribution (V)

3.34 L/kg Interval 0.293 to 10.85

PRIMARY outcome

Timeframe: up to 3 days of study drug administration and 10 days of safety monitoring

Population: 32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.

Outcome measures

Measure

Acyclovir Study Design n=28 Participants 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).

Half-life (T1/2)

7.07 h Interval 1.61 to 13.2

PRIMARY outcome

Timeframe: up to 3 dasy of study drug administration and 10 days of safety monitoring

Population: 32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.

Outcome measures

Measure

Acyclovir Study Design n=28 Participants 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).

Maximum Steady State Concentration (Cmaxss)

11.1 mg/L Interval 4.59 to 110.0

PRIMARY outcome

Timeframe: up to 3 days of study drug administration and 10 days of safety monitoring

Population: 32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.

Outcome measures

Measure

Acyclovir Study Design n=28 Participants 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).

Steady State Concentration at 50% of the Dosing Interval (C50ss)

6.33 mg/L Interval 3.38 to 65.7

PRIMARY outcome

Timeframe: up to 3 days of study drug administration and 10 days of safety monitoring

Population: 32 infants enrolled. 2 infants died. 2 infants did not contribute PK samples to the analysis. 28 contributed PK samples to the final analysis.

Outcome measures

Measure

Acyclovir Study Design n=28 Participants 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).

Minimum Steady State Concentration (Cminss)

4.15 mg/L Interval 2.19 to 39.3

Adverse Events

Acyclovir Study Design

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Acyclovir Study Design n=32 participants at risk 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).
General disorders Death	6.2% 2/32 • Number of events 2 • Up to 3 days of study drug administration and 10 days of safety monitoring
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroblastoma	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Respiratory, thoracic and mediastinal disorders Neonatal asphyxia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring

Other adverse events

Measure	Acyclovir Study Design n=32 participants at risk 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).
Blood and lymphatic system disorders Haemolytic anemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Cardiac disorders Cardiomegaly	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Congenital, familial and genetic disorders Atrial septal defect	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Congenital, familial and genetic disorders Congenital cardiovascular anomaly	21.9% 7/32 • Number of events 7 • Up to 3 days of study drug administration and 10 days of safety monitoring
Congenital, familial and genetic disorders Nonketotic hyperglycinaemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Congenital, familial and genetic disorders Patent ductus arteriosus	9.4% 3/32 • Number of events 3 • Up to 3 days of study drug administration and 10 days of safety monitoring
Congenital, familial and genetic disorders Ventricular septal defect	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Endocrine disorders Adrenal insufficiency	9.4% 3/32 • Number of events 3 • Up to 3 days of study drug administration and 10 days of safety monitoring
Hepatobiliary disorders Hyperbilirubinaemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Hepatobiliary disorders Hyperbilirubinaemia neonatal	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Infections and infestations Sepsis	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Investigations Blood creatinine abnormal	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Investigations Blood creatinine increased	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Investigations Electrocardiogram QT prolonged	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Metabolism and nutrition disorders Electrolyte imbalance	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Metabolism and nutrition disorders Hyperglycaemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Metabolism and nutrition disorders Hyperkalaemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Metabolism and nutrition disorders Hypoalbuminaemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Metabolism and nutrition disorders Hypocalcaemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Metabolism and nutrition disorders Neonatal hyponatraemia	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Nervous system disorders Intraventricular haemorrhage neonatal	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Renal and urinary disorders Renal failure	6.2% 2/32 • Number of events 2 • Up to 3 days of study drug administration and 10 days of safety monitoring
Respiratory, thoracic and mediastinal disorders Apnoea	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Respiratory, thoracic and mediastinal disorders Chronic respiratory disease	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Respiratory, thoracic and mediastinal disorders Infantile apnoeic attack	6.2% 2/32 • Number of events 2 • Up to 3 days of study drug administration and 10 days of safety monitoring
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Respiratory, thoracic and mediastinal disorders Respiratory distress	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring
Skin and subcutaneous tissue disorders Dermatitis diaper	3.1% 1/32 • Number of events 1 • Up to 3 days of study drug administration and 10 days of safety monitoring

Additional Information

P. Brian Smith, MD MPH MHS

Duke Clinical Research Institute

Phone: 919-668-8951

Email: brian.smith@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place