Clinical Trial Results:
An Open-label Study Evaluating the Safety and Efficacy of Long-term Dosing of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune (Idiopathic) Thrombocytopenia Purpura (ITP)
Summary
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EudraCT number |
2009-016203-32 |
Trial protocol |
ES Outside EU/EEA |
Global end of trial date |
12 Jan 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Jul 2017
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First version publication date |
16 Jul 2017
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Other versions |
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 |
20090340
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01071954 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Amgen Inc.
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Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
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Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
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Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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-000653-PIP01-09 | ||
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 |
12 Jan 2017
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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 |
12 Jan 2017
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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 evaluate the safety of romiplostim as a long-term treatment
in pediatric thrombocytopenic subjects with ITP.
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Protection of trial subjects |
This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines, United States Food and Drug Administration (FDA) GCP regulations/guidelines, and the GCP regulations/guidelines to all regions where the study was conducted.
The investigator submitted the protocol, informed consent form, investigators brochure, and any other relevant supporting information to the appropriate IEC or IRB for review and approval before study initiation. Amendments to the protocol were approved by the IEC/IRB and the local regulatory agencies, as appropriate, before the implementation of changes to the study.
The investigator or his/her designee informed the subject of all aspects pertaining to the subject’s participation in the study before any screening procedures or investigational drug was administered.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Dec 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 |
Australia: 7
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Country: Number of subjects enrolled |
Canada: 6
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
United States: 51
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Worldwide total number of subjects |
66
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EEA total number of subjects |
2
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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) |
37
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Adolescents (12-17 years) |
28
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Adults (18-64 years) |
1
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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 was conducted at 28 centers in Australia, Canada, Spain, and the United States. Participants were enrolled from 30 December 2009 until 19 February 2015. | ||||||||||||||||||||||
Pre-assignment
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Screening details |
Pediatric subjects who completed a romiplostim study for the treatment of thrombocytopenia in pediatric subjects with ITP were eligible to participate in this study. | ||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Arms
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Arm title
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Romiplostim | ||||||||||||||||||||||
Arm description |
Participants received romiplostim administered by subcutaneous injection once a week. The starting dose of romiplostim was 1 μg/kg; weekly dose increases continued in increments of 1 μg/kg/week to a maximum dose of 10 μg/kg in an attempt to reach a target platelet count of between 50 x 10^9/L and 200 x 10^9/L. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Romiplostim
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Investigational medicinal product code |
AMG 531
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Other name |
Nplate
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administered by subcutaneous injection with a starting dose of 1 μg/kg/week up to a maximum dose of 10 μg/kg.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Romiplostim
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Reporting group description |
Participants received romiplostim administered by subcutaneous injection once a week. The starting dose of romiplostim was 1 μg/kg; weekly dose increases continued in increments of 1 μg/kg/week to a maximum dose of 10 μg/kg in an attempt to reach a target platelet count of between 50 x 10^9/L and 200 x 10^9/L. |
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End point title |
Number of Participants with Adverse Events [1] | ||||||||||||||||||||||||||||||||||
End point description |
The adverse event severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grading scale.
A serious adverse event was defined as an adverse event that met at least one of the following serious criteria:
• fatal
• life threatening (places the subject at immediate risk of death)
• required in-patient hospitalization or prolongation of existing hospitalization
• resulted in persistent or significant disability/incapacity
• congenital anomaly/birth defect
• other medically important serious event.
The investigator assessed whether each adverse event was possibly related to the investigational product.
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End point type |
Primary
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End point timeframe |
From first dose of study drug until 1 week after last dose. The median (Q1, Q3) duration of treatment was 135.0 weeks (95.0 weeks, 184.0 weeks).
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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: No hypotheses were tested. The statistical analysis in this open-label extension study were descriptive in nature. |
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Notes [2] - Enrolled participants who received at least one dose of romiplostim. |
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No statistical analyses for this end point |
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End point title |
Duration Adjusted Rate of Treatment Emergent Adverse Events [3] | ||||||||||||||||||||||||||||||||||||
End point description |
Exposure adjusted rate was defined as total number of events divided by duration of time when subjects were under observation.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to 1 week after the last dose. The median (Q1, Q3) duration of treatment was 135.0 weeks (95.0 weeks, 184.0 weeks).
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Notes [3] - 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: No hypotheses were tested. The statistical analysis in this open-label extension study were descriptive in nature. |
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Notes [4] - Total subject years on study = 181.8 |
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No statistical analyses for this end point |
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End point title |
Number of Participants who Developed Antibodies to Romiplostim [5] | ||||||||||||||||||
End point description |
Two validated assays were used to test for antibodies to romiplostim / the thrombopoietin-mimetic peptide component of romiplostim (TMP). The first was an immunoassay to confirm the presence of antibodies. The second was a cell-based bioassay to detect neutralizing or inhibitory effects in vitro. If a sample was positive in both assays, a participant was defined as positive for neutralizing antibodies.
Transient antibodies are those positive post-baseline but negative at the last time point tested.
Persistent antibodies were those positive at the last time point tested.
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End point type |
Primary
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End point timeframe |
Once a year until the end of treatment
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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: No hypotheses were tested. The statistical analysis in this open-label extension study were descriptive in nature. |
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Notes [6] - Subjects with a post-baseline result |
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No statistical analyses for this end point |
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End point title |
Number of Participants who Developed Antibodies to Endogenous Thrombopoietin [7] | ||||||||||||||||||
End point description |
Two validated assays were used to test for antibodies to endogenous thrombopoietin (TPO). The first was an immunoassay to confirm the presence of antibodies. The second was a cell-based bioassay to detect neutralizing or inhibitory effects in vitro. If a sample was positive in both assays, a participant was defined as positive for neutralizing antibodies.
Transient antibodies are those positive post-baseline but negative at the last time point tested.
Persistent antibodies were those positive at the last time point tested.
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End point type |
Primary
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End point timeframe |
Once a year until the end of treatment
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Notes [7] - 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: No hypotheses were tested. The statistical analysis in this open-label extension study were descriptive in nature. |
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Notes [8] - Subjects with a post-baseline result |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with a Platelet Response | ||||||||
End point description |
Platelet response was defined as any platelet counts ≥ 50 x 10^9/L in the absence of rescue medication
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End point type |
Secondary
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End point timeframe |
Every 4 weeks for the duration of treatment
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Notes [9] - Enrolled participants who received at least one dose of romiplostim. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants who used Concomitant ITP Therapy | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From baseline to the end of treatment
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Notes [10] - Enrolled participants who received at least one dose of romiplostim. |
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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 |
From first dose of study drug until 1 week after last dose. The median (Q1, Q3) duration of treatment was 135.0 weeks (95.0 weeks, 184.0 weeks).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Romiplostim
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Reporting group description |
Participants received romiplostim administered by subcutaneous injection once a week. The starting dose of romiplostim was 1 μg/kg; weekly dose increases continued in increments of 1 μg/kg/week to a maximum dose of 10 μg/kg in an attempt to reach a target platelet count of between 50 x 10^9/L and 200 x 10^9/L. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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10 Dec 2011 |
• The sample size was increased from 20 subjects to approximately 100 subjects.
• The sample size was increased from 20 subjects to approximately 100 subjects.
• 36 months treatment duration was added.
• Inclusion/exclusion criteria were updated.
• An end of follow-up visit was added.
• Information about consenting to participate in an optional PK portion of the study was added.
• The number of study centers was increased from 10 to 50 centers.
• The study completion date was changed from December 2012 to December 2014.
• The dosage (and adjustments), administration, and schedule were clarified.
• Medications were added to the list of permitted rescue medications.
• Medications were added to the list of prohibited medications.
• The laboratory sample collection and shipping instructions were changed to include the additional collections of blood smears, biopsies, or aspirate, if necessary.
• The collection of antibody samples was added.
• The activities occurring at the study were clarified.
• Reporting procedures for adverse events were clarified. |
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20 Mar 2012 |
• The pharmacy guide in Appendix E was removed and replaced with the Investigational Product Information Manual to accommodate study center-specific drug distribution options and to ensure that the most current investigational product details were accurately communicated.
• The serious adverse event guidance was updated to reflect a 24-hour rather than 1 work day timeline for reporting serious adverse events. |
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25 Sep 2012 |
• Study contacts and other minor updates were made.
• The definition of the study duration for subjects was updated.
• The serious adverse event reporting language was updated per current Amgen safety guidelines.
• The adverse event reporting language and grading criteria (National Cancer Institute - Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) were changed for consistency within the romiplostim pediatric program. |
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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 |