Clinical Trial Results:
A Phase I, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Telbivudine (LdT) in Children and Adolescents with Chronic Hepatitis B Virus Infection
Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
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Summary
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EudraCT number |
2007-006218-40 |
Trial protocol |
BE DE GB BG Outside EU/EEA |
Global end of trial date |
27 Nov 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jul 2018
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First version publication date |
06 Jul 2018
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Other versions |
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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 |
CLDT600A2104
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00907894 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111 ,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111 ,
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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-000065-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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Nov 2011
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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 |
27 Nov 2011
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of the study was to evaluate the single-dose pharmacokinetics, safety and tolerability of Telbivudine (15mg/kg, 25mg/kg and 600mg) oral solution in pediatric and adolescent subjects (aged 2 to 18 years) infected with chronic hepatitis B (CHB) virus infection.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Feb 2009
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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 Kingdom: 2
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Country: Number of subjects enrolled |
Belgium: 3
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Country: Number of subjects enrolled |
Bulgaria: 4
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Country: Number of subjects enrolled |
Germany: 5
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Country: Number of subjects enrolled |
Egypt: 2
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Country: Number of subjects enrolled |
Philippines: 7
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Worldwide total number of subjects |
23
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EEA total number of subjects |
14
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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) |
0
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Children (2-11 years) |
15
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Adolescents (12-17 years) |
8
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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 |
The study was conducted at 6 centres in 6 countries. | ||||||||||||
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Pre-assignment
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Screening details |
A total of 23 subjects infected with Hepatitis B Virus (HBV) were enrolled in the study. Based on their age, the subjects were stratified to 3 stratums. i.e Stratum 1: 2 to less than 6 years old, Stratum 2: 6 to less than 12 years old and Stratum 3: 13 to 18 years old subjects. | ||||||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
This was an open-label study, hence no blinding was implemented.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Telbivudine 15 mg/kg | ||||||||||||
Arm description |
Single dose of telbivudine 15 mg/kg oral solution was administered once daily to subjects stratified by age (2-<6 years and 6-<12 years). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Telbivudine 15 mg/kg
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Investigational medicinal product code |
LDT600
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Single dose of telbivudine 15 mg/kg oral solution was administered once daily.
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Arm title
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Telbivudine 25 mg/kg | ||||||||||||
Arm description |
Single dose of telbivudine 25 mg/kg oral solution was administered once daily to subjects stratified by age (2-<6 years and 6-<12 years). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Telbivudine 25 mg/kg
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Investigational medicinal product code |
LDT600
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Single dose of telbivudine 25 mg/kg oral solution was administered once daily.
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Arm title
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Telbivudine 600 mg | ||||||||||||
Arm description |
Single dose of telbivudine 600 mg oral solution was administered once daily to subjects stratified by age (13 to 18 years). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Telbivudine 600 mg
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Investigational medicinal product code |
LDT600
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Single dose of telbivudine 600 mg oral solution was administered once daily.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Telbivudine 15 mg/kg
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Reporting group description |
Single dose of telbivudine 15 mg/kg oral solution was administered once daily to subjects stratified by age (2-<6 years and 6-<12 years). | ||
Reporting group title |
Telbivudine 25 mg/kg
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Reporting group description |
Single dose of telbivudine 25 mg/kg oral solution was administered once daily to subjects stratified by age (2-<6 years and 6-<12 years). | ||
Reporting group title |
Telbivudine 600 mg
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Reporting group description |
Single dose of telbivudine 600 mg oral solution was administered once daily to subjects stratified by age (13 to 18 years). | ||
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End point title |
Maximum Observed Plasma Concentration (Cmax) [1] | ||||||||||||||||||||||||||||
End point description |
Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. Analysis was performed in pharmacokinetic (PK) set population which included the subjects with evaluable PK data and no major protocol deviations with impact on PK data. The 'n' signifies those subjects evaluable for this measure for each strata based on age stratification by reporting group, respectively. For n=0, data "0.0" is reported because , EudraCT system is not allowing to report "NA" for not applicable/not available data.
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End point type |
Primary
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End point timeframe |
Pre-dose (0), 1, 2, 3, 4, 8, 12, 24, 32, 48, 72 and 120 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: Descriptive statistics only |
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| Notes [2] - Data should be "NA" for Stratum 3 as n=0, reported '0' to avoid invalid system error [3] - Data should be "NA" for Stratum 3 as n=0, reported '0' to avoid invalid system error [4] - Data should be "NA" for Stratum 1 and 2 as n=0, reported '0' to avoid invalid system error |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Area under the drug concentration-time curve from time zero to 24 hours after dosing(AUC0-24h) [5] | ||||||||||||||||||||||||||||
End point description |
AUC(0-24h) was defined as the area under the drug concentration-time curve calculated using linear trapezoidal summation from time zero to 24 hours after dosing. Analysis was performed in PK set population. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively. For n=0, data "0" is reported because , EudraCT system is not allowing to report "NA" for not applicable/not available data.
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End point type |
Primary
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End point timeframe |
Pre-dose (0), 1, 2, 3, 4, 8, 12 and 24 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: Descriptive statistics only |
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| Notes [6] - The data was not applicable for Stratum 3 and denoted as 0. [7] - The data was not applicable for Stratum 3 and denoted as 0. [8] - The data was not applicable for Stratum 1 and Stratum 2 and denoted as 0. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
AUC From Time Zero to Last Measurable Concentration [AUC (0-t)] [9] | ||||||||||||||||||||||||||||
End point description |
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. It was calculated as the sum of linear trapezoids using non-compartmental analysis. Analysis was performed in PK set population. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively. For n=0, data "0" is reported because , EudraCT system is not allowing to report "NA" for not applicable/not available data.
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End point type |
Primary
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End point timeframe |
Pre-dose (0), 1, 2, 3, 4, 8, 12, 24, 32, 48, 72 and 120 hours post-dose
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| Notes [9] - 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: Descriptive statistics only |
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| Notes [10] - The data was not applicable for Stratum 3 and denoted as 0. [11] - The data was not applicable for Stratum 3 and denoted as 0. [12] - The data was not applicable for Stratum 1 and Stratum 2 and denoted as 0. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
AUC From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] [13] | ||||||||||||||||||||||||||||
End point description |
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). AUC(0-infinity) was estimated as AUC 0-t + C t /λ z, where λ z was the terminal elimination rate constant. Analysis was performed in PK set population. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively. For n=0, data "0" is reported because , EudraCT system is not allowing to report "NA" for not applicable/not available data.
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End point type |
Primary
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End point timeframe |
Pre-dose (0), 1, 2, 3, 4, 8, 12, 24, 32, 48, 72 and 120 hours post-dose
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| Notes [13] - 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: Descriptive statistics only |
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| Notes [14] - The data was not applicable for Stratum 3 and denoted as 0. [15] - The data was not applicable for Stratum 3 and denoted as 0. [16] - The data was not applicable for Stratum 1 and Stratum 2 and denoted as 0. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Oral Total Plasma Clearance (CL/F) [17] | ||||||||||||||||||||||||||||
End point description |
Oral total plasma clearance (CL/F) was calculated as Dose/AUC0-∞, where CL was the clearance of the drug and F was the absolute oral bioavailability. Analysis was performed in PK set population. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively. For n=0, data "0" is reported because , EudraCT system is not allowing to report "NA" for not applicable/not available data.
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End point type |
Primary
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End point timeframe |
Pre-dose(0), 1, 2, 3, 4, 8, 12, 24, 32, 48, 72 and 120 hours post-dose
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| Notes [17] - 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: Descriptive statistics only |
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| Notes [18] - The data was not applicable for Stratum 3 and denoted as 0. [19] - The data was not applicable for Stratum 3 and denoted as 0. [20] - The data was not applicable for Stratum 1 and Stratum 2 and denoted as 0. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Terminal Half-Life [21] | ||||||||||||||||||||||||||||
End point description |
Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body. Analysis was performed in PK set population. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively. For n=0, data "0" is reported because , EudraCT system is not allowing to report "NA" for not applicable/not available data.
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End point type |
Primary
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End point timeframe |
Pre-dose(0), 1, 2, 3, 4, 8, 12, 24, 32, 48, 72 and 120 hours post-dose
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| Notes [21] - 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: Descriptive statistics only |
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| Notes [22] - The data was not applicable for Stratum 3 and denoted as 0 [23] - The data was not applicable for Stratum 3 and denoted as 0 [24] - The data was not applicable for Stratum 1 and Stratum 2 and denoted as 0. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [25] | ||||||||||||||||||||
End point description |
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. All the subjects received study drug were included in the safety analysis set.
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End point type |
Primary
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End point timeframe |
From first patient first treatment up to 30 days following the end of study
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| Notes [25] - 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: Descriptive only |
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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 |
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
LDT600 15 mg/kg solution
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Reporting group description |
Single dose of telbivudine 15mg/kg oral solution was administered once daily to subjects stratified by age (2-<6 years and 6-<12 years). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
LDT600 600 mg solution
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Reporting group description |
Single dose of telbivudine 600 mg oral solution was administered once daily to subjects stratified by age (13 to 18 years). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Telbivudine 25 mg/kg
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Reporting group description |
Single dose of telbivudine 25 mg/kg oral solution was administered once daily to subjects stratified by age (2-<6 years and 6-<12 years). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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21 Sep 2007 |
1) Day 2 clinical laboratory assessments and 32 hour post dose sampling were removed
2) The methods for subject stratification were changed to include substrata
3) Elements of inclusion and exclusion criteria were revised
4) Subjects vomiting within the first 3 hours after dosing were to be withdrawn and replaced.
5)The time period for adverse event follow up was modified |
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16 Jan 2008 |
1) Change of serious adverse event and adverse event reporting process
2) Clarification of strata dosing sequence
3) Additional information provided in dose selection section
4) Removal of the drug preparation procedure from the protocol
5) Addition of pregnancy reporting process
6) Addition of pharmacokinetic sample numbers. |
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30 May 2008 |
1) Change of serious adverse event reporting
2) Additional instruction for use of study drug |
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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. | |||
| Study was terminated after enrollment of 23 of the planned 28 patients as it had met its primary objective, enrollment was slower than anticipated, and health authorities agreed with the sponsor’s dosing proposal from the study data. | |||
