Clinical Trial Results:
A 52-Week Open-Label Extension and Safety Study of Pitavastatin in High-Risk Hyperlipidaemia in Childhood, P/0230/2012, P/0231/2012, P/0232/2012 and P/0233/2012.
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Summary
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EudraCT number |
2011-004983-32 |
Trial protocol |
GR NL FR ES NO IT |
Global end of trial date |
10 Jun 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Feb 2016
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First version publication date |
31 Jul 2015
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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 |
NK-104-4.02EU
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Kowa Research Europe, Ltd
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Sponsor organisation address |
105 Wharfedale Road, Winnersh Triangle, Wokingham, United Kingdom, RG41 5RB
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Public contact |
Regulatory Affairs, Kowa Research Europe, Ltd., +44 (0)118 922 9000,
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Scientific contact |
Regulatory Affairs, Kowa Research Europe, Ltd., +44 (0)118 922 9000,
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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-000300-PIP01-08 EMEA-000054-PIP01-07 EMEA-000302-PIP01-08 EMEA-000301-PIP01-08 | ||
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 |
02 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Jun 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jun 2014
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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 study was to assess the safety of pitavastatin 1 mg QD, 2 mg QD, and 4 mg QD in children or adolescent patients with high-risk hyperlipidaemia over a period of 52 weeks.
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. Each patient was assured of his/her right to withdraw from the study at any time. Close monitoring of all subjects was adhered to throughout the trial conduct.
Patients were discouraged from starting any new medication, both prescribed and over-the-counter, without consulting the Investigator unless the new medication was required for emergency use. In general, any medication not excluded by the protocol was permitted.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
26 Jul 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Netherlands: 48
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Country: Number of subjects enrolled |
Spain: 9
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Greece: 23
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Country: Number of subjects enrolled |
Italy: 26
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Worldwide total number of subjects |
113
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EEA total number of subjects |
113
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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) |
67
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Adolescents (12-17 years) |
46
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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 |
This study included patients who completed the 12-week, double-blind study NK-104-4.01EU (EudraCT 2011-004964-32), but was also open for enrollment by eligible children and adolescents who were not enrolled in the double-blind study. | ||||||||||||||||
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Pre-assignment
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Screening details |
For patients who were not enrolled in the double-blind study, a 5 weeks screening/washout period occurred before the start of dosing. No screening/washout period was required for patients who entered this study upon completion of the double-blind study. | ||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Pitavastatin 1, 2 or 4 mg | ||||||||||||||||
Arm description |
All patients started from 1 mg and were up-titrated to 2 or 4 mg in step-wise manner in an effort to achieve a LDL-C treatment target (<110 mg/dL) so long as the dose was tolerated. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Pitavastatin
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Investigational medicinal product code |
NK-104
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Other name |
PITAVASTATIN CALCIUM
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Pitavastatin tablet 1, 2 or 4 mg were to be taken orally, once daily in the morning. Duration of treatment was 52 weeks.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One Patient was enrolled into the study, but withdrew consent before receiving any study drug. The patient was therefore not included in any specific dose level, but was included in the patient total. |
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Baseline characteristics reporting groups
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Reporting group title |
Pitavastatin 1, 2 or 4 mg
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Reporting group description |
All patients started from 1 mg and were up-titrated to 2 or 4 mg in step-wise manner in an effort to achieve a LDL-C treatment target (<110 mg/dL) so long as the dose was tolerated. | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pitavastatin 1, 2 or 4 mg
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Reporting group description |
All patients started from 1 mg and were up-titrated to 2 or 4 mg in step-wise manner in an effort to achieve a LDL-C treatment target (<110 mg/dL) so long as the dose was tolerated. | ||
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End point title |
Percent change in LDL-C [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline to week 52 with LOCF.
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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: This was an open-label safety study without any comparators; therefore, no formal statistical analysis for efficacy end points were executed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentages of patients who achieved AHA minimal (130 mg/dL [3.4 mmol/L]) and ideal (110 mg/dL [2.8 mmol/L]) LDL-C targets | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From baseline over 52 weeks of treatment.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent changes in HDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), TG, apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From baseline to week 52 with LOCF.
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Changes in TC:HDL-C ratio, non-HDL-C:HDL-C ratio, and Apo B:Apo A1 ratio | ||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From baseline to week 52 with LOCF.
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Adverse events information
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Timeframe for reporting adverse events |
Adverse event reporting began from the time of informed consent/assent and ended at the conclusion of the study unless an unresolved adverse event was still being followed.
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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 |
Pitavastatin 1, 2 or 4 mg
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Reporting group description |
All patients started from 1 mg and were up-titrated to 2 or 4 mg in step-wise manner in an effort to achieve a LDL-C treatment target (<110 mg/dL) so long as the dose was tolerated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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22 May 2012 |
Amendment 2 (Protocol v3.0) was written to modify the language about removing patients from the study due to failure to achieve the target LDL-C level of <130 mg/dL (3.4 mmol/L). Due to the lack of approved statin treatments available to paediatric patients at the time the study began, the study Investigators requested that they have discretion to maintain children in the trial if it was felt that there was no better therapy available outside the confines of the trial, rather than being required to withdraw them based solely on the LDL-C levels achieved. After the Investigator Meeting, this proposed modification to the study was presented to and supported by the independent DMC for this study. |
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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 | |||
