Trial Outcomes & Findings for Evaluation of the Pharmacokinetics (PK) and Pharmacodymamics (PD) of Ganciclovir (GCV) in Premature Infants Receiving Treatment for Cytomegalorivus (CMV) Infection (NCT NCT01602614)

NCT ID: NCT01602614

Last Updated: 2020-06-02

Results Overview

A series of blood samples will be collected to assess the ganciclovir levels in the blood at the following time points: 0 hour (immediately prior to intravenous (IV) ganciclovir dose; within 15 min prior to dose), 1 hour (immediately after the end of the IV ganciclovir dose; within 15 min after dose), 2-3 hour, 5-7 hour, and 10-12 hour; required amount of whole blood for plasma ganciclovir determination at each time point is at least 0.2 mL

• Recruitment status: COMPLETED
• Target enrollment: 18 participants
• Primary outcome timeframe: within 12 hours after dose administration
• Results posted on: 2020-06-02

Participant Flow

Participant milestones

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.	Group 2 ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.	Group 3 ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.
Overall Study STARTED	0	10	8	0
Overall Study COMPLETED	0	10	8	0
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of the Pharmacokinetics (PK) and Pharmacodymamics (PD) of Ganciclovir (GCV) in Premature Infants Receiving Treatment for Cytomegalorivus (CMV) Infection

Baseline characteristics by cohort

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=10 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=8 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment	Total n=18 Participants Total of all reporting groups
Age, Customized Age (days)	—	63.2 days STANDARD_DEVIATION 18.0 • n=7 Participants	16.5 days STANDARD_DEVIATION 7.4 • n=5 Participants	—	42.4 days STANDARD_DEVIATION 27.6 • n=21 Participants
Sex: Female, Male Female	—	2 Participants n=7 Participants	1 Participants n=5 Participants	—	3 Participants n=21 Participants
Sex: Female, Male Male	—	8 Participants n=7 Participants	7 Participants n=5 Participants	—	15 Participants n=21 Participants
Race/Ethnicity, Customized Race · Asian	—	1 Participants n=7 Participants	0 Participants n=5 Participants	—	1 Participants n=21 Participants
Race/Ethnicity, Customized Race · Black or African American	—	3 Participants n=7 Participants	0 Participants n=5 Participants	—	3 Participants n=21 Participants
Race/Ethnicity, Customized Race · White	—	5 Participants n=7 Participants	7 Participants n=5 Participants	—	12 Participants n=21 Participants
Race/Ethnicity, Customized Race · More than one race	—	1 Participants n=7 Participants	1 Participants n=5 Participants	—	2 Participants n=21 Participants
Region of Enrollment United States	—	10 Participants n=7 Participants	8 Participants n=5 Participants	—	18 Participants n=21 Participants

PRIMARY outcome

Timeframe: within 12 hours after dose administration

Population: No subjects were enrolled in Group 1 and Group 4. One subject in Group 3 did not collect full panel therefore no pk analyzed.

A series of blood samples will be collected to assess the ganciclovir levels in the blood at the following time points: 0 hour (immediately prior to intravenous (IV) ganciclovir dose; within 15 min prior to dose), 1 hour (immediately after the end of the IV ganciclovir dose; within 15 min after dose), 2-3 hour, 5-7 hour, and 10-12 hour; required amount of whole blood for plasma ganciclovir determination at each time point is at least 0.2 mL

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=10 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=7 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Plasma Pharmacokinetics Parameters for Ganciclovir Area Under the Curve at 12 Hours (AUC12mgxh/L)	—	47.2 mgxh/L Standard Error 21.5	76.8 mgxh/L Standard Error 39.6	—

SECONDARY outcome

Timeframe: within 12 hours after dose administration

Population: No subjects were enrolled in Group 1 and Group 4. One subject in Group 3 did not collect full panel therefore no pk analyzed.

Looking at the Pharmacokinetics (PK) parameters for Ganciclovir (GCV). A series of blood samples was collected to assess the ganciclovir levels in the blood at the following time points: 0 hour (immediately prior to intravenous (IV) ganciclovir dose; within 15 min prior to dose), 1 hour (immediately after the end of the IV ganciclovir dose; within 15 min after dose), 2-3 hour, 5-7 hour, and 10-12 hour.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=10 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=7 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Plasma Pharmacokinetics Parameters for Ganciclovir, Including Maximum Serum Concentration (Cmax mg/L).	—	7.9 mg/L Standard Error 2.2	10.0 mg/L Standard Error 5.4	—

SECONDARY outcome

Timeframe: within 12 hours after dose administration

Population: No subjects were enrolled in Group 1 and Group 4. One subject in Group 3 did not collect full panel therefore no pk analyzed.

Looking at the Pharmacokinetics (PK) parameters for Ganciclovir (GCV). A series of blood samples was collected to assess the ganciclovir levels in the blood at the following time points: 0 hour (immediately prior to intravenous (IV) ganciclovir dose; within 15 min prior to dose), 1 hour (immediately after the end of the IV ganciclovir dose; within 15 min after dose), 2-3 hour, 5-7 hour, and 10-12 hour.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=10 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=7 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Plasma Pharmacokinetics Parameters for Ganciclovir for Half-life (T1/2 hr).	—	5.0 Hr Standard Error 3.5	7.2 Hr Standard Error 2.2	—

SECONDARY outcome

Timeframe: within 12 hours after dose administration

Population: No subjects were enrolled in Group 1 and Group 4. One subject in Group 3 did not collect full panel therefore no pk analyzed.

Looking at the Pharmacokinetics (PK) parameters for Ganciclovir (GCV). A series of blood samples was collected to assess the ganciclovir levels in the blood at the following time points: 0 hour (immediately prior to intravenous (IV) ganciclovir dose; within 15 min prior to dose), 1 hour (immediately after the end of the IV ganciclovir dose; within 15 min after dose), 2-3 hour, 5-7 hour, and 10-12 hour.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=10 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=7 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Plasma Pharmacokinetics Parameters for Ganciclovir for Clearance (Cl L/hr/kg).	—	0.1 L/hr/kg Standard Error 0.1	0.1 L/hr/kg Standard Error 0.0	—

SECONDARY outcome

Timeframe: within 12 hours after dose administration

Population: No subjects were enrolled in Group 1 and Group 4. One subject in Group 3 did not collect full panel therefore no pk analyzed.

Looking at the Pharmacokinetics (PK) parameters for Ganciclovir (GCV). A series of blood samples was collected to assess the ganciclovir levels in the blood at the following time points: 0 hour (immediately prior to intravenous (IV) ganciclovir dose; within 15 min prior to dose), 1 hour (immediately after the end of the IV ganciclovir dose; within 15 min after dose), 2-3 hour, 5-7 hour, and 10-12 hour.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=10 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=7 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Plasma Pharmacokinetics Parameters for Ganciclovir for Volume of Distribution (Vd L).	—	1.4 L Standard Error 0.6	1.1 L Standard Error 0.3	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK clearance (CL L/hr/kg) results to the whole blood CMV viral load data.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics (Clearance (CL) With Whole Blood Cytomegalovirus (CMV) Viral Load.	—	0.13667 L/hr/kg Standard Deviation 0.08311	0.08000 L/hr/kg Standard Deviation 0.02530	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK results maximum serum concentration (Cmax) to the CMV viral load data.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Maximum Serum Concentration (Cmax) With Whole Blood Cytomegalovirus (CMV) Viral Load.	—	7.99833 mg/L Standard Deviation 2.78494	10.22500 mg/L Standard Deviation 5.82284	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK results area under the curve (AUC12-mgxh/L) to the whole blood CMV viral load data.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Area Under the Curve (AUC12) With Whole Blood Cytomegalovirus (CMV) Viral Load.	—	50.77167 mgxh/L Standard Deviation 26.46657	79.58833 mgxh/L Standard Deviation 42.67824	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK results half-life (T1/2 hr) to the whole blood CMV viral load data.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Half-life (T1/2) With Whole Blood Cytomegalovirus (CMV) Viral Load.	—	5.37333 hr Standard Deviation 4.34650	7.36167 hr Standard Deviation 2.39133	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK results volume of distribution (Vd L) to the whole blood CMV viral load data.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Volume of Distribution (Vd) With Whole Blood Cytomegalovirus (CMV) Viral Load.	—	1.36333 L Standard Deviation 0.74457	1.06000 L Standard Deviation 0.35491	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK results clearance (Cl L/hr/kg) to the clearance of CMV in the urine samples

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Clearance (Cl) With Clearance of CMV in Urine	—	0.12000 L/hr/kg Standard Deviation 0.08025	0.07667 L/hr/kg Standard Deviation 0.02160	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK results to the Cmax with clearance of CMV in the urine samples

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Maximum Serum Concentration (Cmax) With Clearance of CMV in Urine.	—	8.93000 mg/L Standard Deviation 1.91465	10.58667 mg/L Standard Deviation 5.58772	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK AUC results to the clearance of CMV in the urine samples.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Area Under the Curve (AUC) With Clearance of CMV in Urine.	—	55.23667 mgxhr/L Standard Deviation 23.90314	81.46333 mgxhr/L Standard Deviation 41.29835	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK half-life results to the clearance of CMV in the urine samples.

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Maximum Serum Half Life (T1/2) With Clearance of CMV in Urine.	—	6.25000 hr Standard Deviation 4.04001	7.39667 hr Standard Deviation 2.36849	—

SECONDARY outcome

Timeframe: 6 weeks

Population: No subjects were enrolled in Group 1 and Group 4. Four (4) Group 2 subjects and two (2) Group 3 subjects did not have viral loads for at least two (2) time points, therefore correlation could not be performed.

Comparing the GCV PK Vd results to the clearance of CMV in the urine samples

Outcome measures

Measure	Group 1 ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 2 n=6 Participants ≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment	Group 3 n=6 Participants ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment	Group 4 ≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment
Correlation of Ganciclovir Plasma Pharmacokinetics Volume of Distribution (Vd) With Clearance of CMV in Urine.	—	1.35000 L Standard Deviation 0.74814	0.97333 L Standard Deviation 0.25073	—

Adverse Events

Group 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 4

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

David Kimberlin, MD

University of Alabama at Birmingham

Phone: 205 934-2424

Email: Dkimberlin@peds.uab.edu

Results disclosure agreements

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