Clinical Trial Results:
A Multi-centre, Open-label Study Evaluating the Safety and Tolerability of Colestilan (MCI-196) in Paediatric Subjects with Chronic Kidney Disease Stages 3b to 5 and with Hyperphosphataemia not on Dialysis
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Summary
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EudraCT number |
2012-002582-35 |
Trial protocol |
GB DE |
Global end of trial date |
14 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Feb 2016
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First version publication date |
19 Feb 2016
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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 |
MCI-196-E16
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01818687 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Mitsubishi Tanabe Pharma Corporation
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Sponsor organisation address |
17-10, Nihonbashi-Koamicho, Chuo-ku, Tokyo, Japan, 103-8405
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Public contact |
General Information, Mitsubishi Tanabe Pharma Europe Ltd , regulatory@mt-pharma-eu.com
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Scientific contact |
General Information, Mitsubishi Tanabe Pharma Europe Ltd, regulatory@mt-pharma-eu.com
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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-000878-PIP02-11 | ||
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 |
18 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jan 2015
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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 objective of this study was to assess safety and tolerability of colestilan in paediatric subjects (aged 2 years to <18 years) with CKD Stages 3b to 5, diagnosed with hyperphosphataemia, who were not on dialysis.
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Protection of trial subjects |
1 For subjects on phosphate binders: during the wash-out period, a max of 4 weeks, subjects stopped their current phosphate binder treatment, which was likely to cause a rise in P levels. The increase in P was not dangerous for a short period of time and once the required P level was reached, the subject was randomised and treated with Colestilan (MCI-196). The level to which the P is required to rise was specified in inclusion criteria 6 and 7.
2 When specifying the amount of blood to be drawn the following guidelines were used: trial-related blood loss (including loss in the procedure) should not exceed 3% of total blood volume during a period of 4 weeks and should not exceed 1% total blood volume at any single time.
Subjects were enrolled to the study only if they could safely provide 8 ml of blood at each visit.
3 When investigating new drugs there is always a risk of unexpected side effects and occasionally allergic reactions. Subjects were closely monitored during the study.
4 Rescue treatment: Hyperphosphataemia, after the max dose of Colestilan (MCI-196) (BSAeq of 15 g/day) was reached, the subject was either withdrawn from the study or the Investigator added CBPB as rescue medication, in addition to the max dose of Colestilan (MCI-196). Adjustment of dosing of vitamin D/analogues was permitted during the study to correct hypocalcaemia. The appropriate doses of rescue treatment were decided by the Investigator based on his/her clinical experience.
5 Consent/assent process: Enough time was provided to the subject/parent/caregiver to consider participation in the study. In addition to the patient information sheet and consent/assent forms, a study flipchart was provided to all sites, which was used as a tool to help explain/discuss aspects of the study in more detail.
6 Tablet intake - it is known that tablets can be difficult to swallow, especially by very young children. The IMP was made available also in granule formulation.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jun 2013
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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 |
Germany: 2
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Country: Number of subjects enrolled |
United Kingdom: 2
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Worldwide total number of subjects |
4
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EEA total number of subjects |
4
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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) |
3
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Adolescents (12-17 years) |
1
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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 |
Subjects were recruited from those patients with hyperphosphataemia who were already attending the clinics for the treatment of CKD stages 3b to 5. | ||||||
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Pre-assignment
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Screening details |
The study comprised of a screening period (1 to 4 weeks) and a wash-out period (1 to 4 weeks). A total of 14 subjects were screened. 10 subjects were withdrawn before randomisation (screen failed). | ||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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MCI-196 (All Subjects) | ||||||
Arm description |
All study subjects were treated for 17 weeks. The starting daily doses of colestilan (MCI-196) was the body surface area equivalent (BSAeq) of 6 g/day in adults, (i.e., 3.47 g/m²/day), oral, divided doses with food. The colestilan dose was titrated up within 3 days of the visit, based on the serum P level and/or the judgement of the Investigator, whichever was more suitable for the best care of the subject. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Colestilan
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Investigational medicinal product code |
MCI-196
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Other name |
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Pharmaceutical forms |
Granules, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 gram tablets and granules of approximately 20 mg packaged in 2 g or 3 g sachets
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Baseline characteristics reporting groups
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Reporting group title |
MCI-196 (All Subjects)
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Reporting group description |
All study subjects were treated for 17 weeks. The starting daily doses of colestilan (MCI-196) was the body surface area equivalent (BSAeq) of 6 g/day in adults, (i.e., 3.47 g/m²/day), oral, divided doses with food. The colestilan dose was titrated up within 3 days of the visit, based on the serum P level and/or the judgement of the Investigator, whichever was more suitable for the best care of the subject. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
MCI-196 (All Subjects)
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Reporting group description |
All study subjects were treated for 17 weeks. The starting daily doses of colestilan (MCI-196) was the body surface area equivalent (BSAeq) of 6 g/day in adults, (i.e., 3.47 g/m²/day), oral, divided doses with food. The colestilan dose was titrated up within 3 days of the visit, based on the serum P level and/or the judgement of the Investigator, whichever was more suitable for the best care of the subject. | ||
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End point title |
Percentage of subjects who, due to hyperphosphataemia, require rescue treatment and/or discontinuation of therapy with colestilan (MCI-196) [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline to Week 17
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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 study was terminated prematurely. From the limited data collected in this study, due to small sample size, no analysis of the data was conducted nor can any reasonable conclusions be made. |
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| Notes [2] - This study was prematurely terminated. No statistical analyses were completed. |
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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 |
All adverse events (AE) that occurred from the time written informed consent/assent was taken until the end of study or discontinuation were recorded in the source documents and reported in the CRF.
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Adverse event reporting additional description |
AEs were classified as 'treatment emergent' (i.e. TEAEs or serious TEAEs) if they occurred following administration of IMP. All events reported in this database are treatment emergent.
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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 |
18
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Reporting groups
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Reporting group title |
MCI-196 (All subjects)
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Reporting group description |
All study subjects were treated for 17 weeks. The starting daily doses of colestilan (MCI-196) was the body surface area equivalent (BSAeq) of 6 g/day in adults, (i.e., 3.47 g/m²/day), oral, divided doses with food. The colestilan dose was titrated up within 3 days of the visit, based on the serum P level and/or the judgement of the Investigator, whichever was more suitable for the best care of the subject. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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. | |||||||
| There were significant challenges to recruitment in all age groups and in this patient population. The study was terminated early due to the withdrawal of the MAA. | |||||||
