Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00614523
Collaborator
(none)
250
2
88.3
Study Details
Study Description
Brief Summary
The Data Monitoring Committee (DMC) for study 20060198 recommended that all subjects discontinue treatment of study drug and continue to be followed for long term follow-up. Amgen adopted the DMC recommendation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a Phase 2, multicenter, randomized, double blind, placebo controlled study designed to assess the efficacy and safety of romiplostim (formerly, AMG 531) treatment in thrombocytopenic MDS patients. The study is composed of a 26-week placebo controlled test treatment period (romiplostim versus Placebo), a 4 week interim wash-out period, a 24-week placebo controlled extended treatment period, and a 4-week follow-up period followed by an End of Study (EOS) visit. During the interim wash-out period, a bone marrow biopsy will be performed in the absence of growth factor to assess changes in the marrow. In the extended treatment period, safety assessments will continue and participants will be allowed to receive any standard of care treatments for MDS. Patients will be followed for survival for an additional 60 months following the End of Study (EOS) visit.
Study Design
Study Type:
Interventional
Actual Enrollment
:
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Supportive Care
Official Title:
A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Actual Study Start Date
:
Jul 21, 2008
Actual Primary Completion Date
:
Mar 31, 2011
Actual Study Completion Date
:
Nov 30, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Romiplostim Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
Biological: Romiplostim
Romiplostim is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.
|
| Placebo Comparator: Placebo Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. |
Drug: Placebo
Placebo is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.
|
Outcome Measures
Primary Outcome Measures
- Number of Clinically Significant Bleeding Events [Test Treatment Period (Weeks 1-26)]
A clinically significant bleeding event is defined as any bleeding event of grade ≥ 2 per the modified World Health Organization (WHO) bleeding scale: • Grade 0 = no bleeding • Grade 1 = petechia or mucosal or retinal bleeding not requiring intervention • Grade 2 = melena, hematemesis, hematuria, hemoptysis • Grade 3 = bleeding required red cell transfusion • Grade 4 = retinal bleeding with visual impairment • Grade 5 = non-fatal cerebral bleeding • Grade 6 = fatal cerebral bleeding • Grade 7 = fatal non-cerebral bleeding. Bleeding events that continue for more than 7 days were counted as separate events every eighth day. Multiple events that arose from one organ system on one day were collapsed into one single event. Bleeding events with a start date between the first dose date and the last dose date of the test treatment period+7 days are included.
Secondary Outcome Measures
- Annualized Rate of Platelet Transfusion Events [Test Treatment Period (Weeks 1-26)]
A discrete platelet transfusion is any number of platelet transfusion administered within a 3-day period. Transfusions administered more than 3 days apart are counted as separate events. Transfusion given in the absence of any bleeding, when platelet count is >10x10^9/L, is not counted as a platelet transfusion event. Events with start date between the first dose date and the last dose date of the test treatment period +7 days are included. Exposure adjusted event rate per 100 patient-years = (events / patient-years * 100). Patient Year = total patient years of exposure to investigational product during 26 weeks test treatment period.
- Annualized Rate of Overall Bleeding Events [Test Treatment Period (Weeks 1-26)]
The time from first dose of study drug to the last dose of 26-week test treatment period. A bleeding event is defined as any bleeding event reported during the test treatment period. Bleeding events that continue for more than 7 days are counted as separate events every eighth day. Multiple events that arose from one organ system on one day are collapsed into one single event. Exposure adjusted event rate per 100 patient-years = events / patient-year * 100).
- Annualized Rate of Total Platelet Transfusion Units [Test Treatment Period (Weeks 1-26)]
The time from first dose of study drug to the last dose of 26-week test treatment period. A unit of platelets is defined as a single pack of pooled platelet-rich plasma comprised of 6 to 8 individual platelet concentrate packs (200 to 400 mL), a single pack of pooled buffy-coat concentrate, or 1 apheresis (single donor) concentrate. Exposure adjusted event rate per 100 patient-years = events / patient-years * 100.
- Number of Participants With Platelet Hematologic Improvement (HI-P) [Test Treatment Period (Weeks 1-26)]
Platelet Hematologic Improvemen defined by the international working group (IWG) as: an absolute increase in platelet count of ≥ 30 x 10^9/L for a patient starting with a platelet count of ≥ 20 x 10^9/L or an increase in platelet count from < 20 x 10^9/L to ≥ 20 x 10^9/L and by at least 100% in a patient that started with a platelet count < 20 x 10^9/L. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint.
- Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions [Test Treatment Period (Weeks 1-26)]
Duration for participants who did not report HI-P during the period is 0. A platelet hematologic improvement (HI-P) is defined by an MDS International Working criteria as patients with a baseline platelet count of ≥ 20 x 10^9/L achieving an absolute increase of ≥ 30 x 10^9/L or increasing the platelet count to above 20 x 10^9/L and by at least 100% in patients with a baseline of < 20 x 10^9/L for at least 8 consecutive weeks. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint. The durations of HI-P are cumulative if more than one incidence occurred. Exposure adjusted event rate per 100 patient-weeks = total number of weeks / patient-weeks * 100.
- Number of Participants Who Died [From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012.]
- Time to Death [From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012.]
Overall survival was calculated using Kaplan-Meier methods. For patients who discontinued early, additional information from the long term follow-up are added (closest available follow-up information up to 58 weeks).
- Kaplan-Meier Estimate of Survival at Month 12 [Month 12, with a data cut-off date of 20 July 2012.]
Overall survival was calculated using Kaplan-Meier methods.
- Annualized Rate of Patient-reported Bleeding Events [Test Treatment Period (Weeks 1-26)]
The number of bleeding events was obtained from the thrombocytopenia symptoms (Th-symptoms) survey. Patients reported spontaneous bleeding to have occurred 0, 1 or 2, 3 or 4, 5 or 6, or 7 or more times in the past week. The lower threshold of bleeding counts is used for conservative purposes (i.e., the "3" is used for the response option of "3 or 4 times"). Exposure adjusted event rate per 100 patient-years = number of events / patient-year * 100.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria: • Diagnosis of MDS using the World Health Organization (WHO) classification for myeloid neoplasms as assessed during the screening period. • Per MDS International Prognostic Scoring System (IPSS), low or intermediate-1 risk MDS as assessed during the screening period. • Mean of the 2 platelet counts taken within 4 weeks prior to randomization must be: - ≤ 20 x 109/L, (with no individual count >30 x 109/L during the screening period), with or without history of bleeding associated with diagnosis of MDS, OR
- ≤ 50 x 109/L, (with no individual count >60 x 109/L during the screening period) with a history of bleeding associated with the diagnosis of MDS. • Patients must be ≥18 and ≤ 90 years of age at time of informed consent. Patients between 85 and 90 years of age must have been diagnosed with MDS ≤ 5 years from study start. • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. • Adequate liver function, as evidenced by alanine aminotransferase (ALT) ≤ 3 times laboratory normal range, aspartate aminotransferase (AST) ≤ 3 times laboratory normal range and total bilirubin ≤ 2.0 times laboratory normal range. (Adequate liver function for patients with confirmed diagnosis of Gilbert's Disease evidenced by ALT ≤ 3 times laboratory normal range, and AST ≤ 3 times laboratory normal range.) • Serum creatinine concentration ≤ 2 mg/dl (≤176.8 μmol/L). • Bone marrow biopsy and aspirate with cytogenetics within 3 months of starting first dose of investigational product. • Written Informed Consent. Exclusion Criteria: • Have ever received any disease-modifying treatment for MDS. • Previously diagnosed with intermediate-2 or high risk MDS using the IPSS. • Prior history of leukemia, aplastic anemia, or other non-MDS related bone marrow stem cell disorder. • Prior history of hematopoietic stem cell transplantation. • Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count >1,000/μL) or known diagnosis of Chronic Myelomonocytic Leukemia per French-American-British Classification System for MDS (FAB) criteria. • Prior malignancy (other than in situ cervical cancer, non-melanoma skin cancer, or in situ carcinoma) unless treated with curative intent and without evidence of disease for ≥ 3 years before randomization. • Active or uncontrolled infections. • Unstable angina, congestive heart failure (New York Heart Association [NYHA] > class II), uncontrolled hypertension (diastolic >100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction. • History of arterial thrombosis (eg, stroke or transient ischemic attack) within the past year. • History of venous thrombosis that currently requires anti-coagulation therapy. • Received Interleukin (IL)-11 within 4 weeks of first dose of investigational product. • Have previously received any thrombopoietic growth factor. • Receipt of granulocyte-colony stimulating factor, (G-CSF), pegylated-G-CSF, or granulocyte macrophage-colony stimulating factor (GM-CSF) within 4 weeks of first dose of investigational product. • Planned receipt of peg-G-CSF or GM-CSF after first dose of investigational product. • Pregnant or breast feeding. • Patients of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator. Amgen recommends double barrier contraception is used for all applicable patients enrolled on this study. A double barrier method is defined as two methods of contraception, for example 2 actual barrier methods, or one actual barrier method and one hormonal method. • Patient has known sensitivity to any recombinant E coli-derived product (eg, Infergen®, Neupogen®, Somatropin, and Actimmune). • Previously enrolled into the 20060198 study or another romiplostim study. • Inability to comply with study procedures. • Patient currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Diao G, Zeng D, Hu K, Ibrahim JG. Modeling event count data in the presence of informative dropout with application to bleeding and transfusion events in myelodysplastic syndrome. Stat Med. 2017 Sep 30;36(22):3475-3494. doi: 10.1002/sim.7351. Epub 2017 May 30.
- Diao G, Zeng D, Hu K, Ibrahim JG. Semiparametric frailty models for zero-inflated event count data in the presence of informative dropout. Biometrics. 2019 Dec;75(4):1168-1178. doi: 10.1111/biom.13085. Epub 2019 Sep 2.
- Giagounidis A, Mufti GJ, Fenaux P, Sekeres MA, Szer J, Platzbecker U, Kuendgen A, Gaidano G, Wiktor-Jedrzejczak W, Hu K, Woodard P, Yang AS, Kantarjian HM. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer. 2014 Jun 15;120(12):1838-46. doi: 10.1002/cncr.28663. Epub 2014 Apr 4.
- Kantarjian HM, Fenaux P, Sekeres MA, Szer J, Platzbecker U, Kuendgen A, Gaidano G, Wiktor-Jedrzejczak W, Carpenter N, Mehta B, Franklin J, Giagounidis A. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial. Lancet Haematol. 2018 Mar;5(3):e117-e126. doi: 10.1016/S2352-3026(18)30016-4. Epub 2018 Jan 26.
- Platzbecker U, Sekeres MA, Kantarjian H, Giagounidis A, Mufti GJ, Jia C, Yang AS, Fenaux P. Relationship of different platelet response criteria and patient outcomes in a romiplostim myelodysplastic syndromes trial. Leukemia. 2014 Dec;28(12):2418-21. doi: 10.1038/leu.2014.253. Epub 2014 Sep 2.
- Sekeres MA, Giagounidis A, Kantarjian H, Mufti GJ, Fenaux P, Jia C, Yang AS, Platzbecker U. Development and validation of a model to predict platelet response to romiplostim in patients with lower-risk myelodysplastic syndromes. Br J Haematol. 2014 Nov;167(3):337-45. doi: 10.1111/bjh.13037. Epub 2014 Jul 14.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00614523
Other Study ID Numbers:
- 20060198
First Posted:
Feb 13, 2008
Last Update Posted:
Jan 18, 2020
Last Verified:
Jan 1, 2020
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | First Subject Enrolled: 21 July 2008, Last Subject Enrolled: 16 December 2010. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Period Title: Overall Study | ||
| STARTED | 83 | 167 |
| COMPLETED | 20 | 36 |
| NOT COMPLETED | 63 | 131 |
Baseline Characteristics
| Arm/Group Title | Placebo | Romiplostim | Total |
|---|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. | Total of all reporting groups |
| Overall Participants | 83 | 167 | 250 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
67
(11.5)
|
68.4
(12)
|
67.9
(11.8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
30
36.1%
|
72
43.1%
|
102
40.8%
|
| Male |
53
63.9%
|
95
56.9%
|
148
59.2%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| White or Caucasian |
79
95.2%
|
156
93.4%
|
235
94%
|
| Black or African American |
0
0%
|
1
0.6%
|
1
0.4%
|
| Hispanic or Latino |
1
1.2%
|
4
2.4%
|
5
2%
|
| Asian |
1
1.2%
|
1
0.6%
|
2
0.8%
|
| Other |
2
2.4%
|
5
3%
|
7
2.8%
|
| Myelodysplastic Syndromes World Health Organization Classification (Number) [Number] | |||
| RA |
5
6%
|
6
3.6%
|
11
4.4%
|
| RARS |
0
0%
|
2
1.2%
|
2
0.8%
|
| RAEB-1 |
9
10.8%
|
24
14.4%
|
33
13.2%
|
| RAEB-2 |
0
0%
|
1
0.6%
|
1
0.4%
|
| RCMD |
55
66.3%
|
114
68.3%
|
169
67.6%
|
| RCMD-RS |
2
2.4%
|
4
2.4%
|
6
2.4%
|
| MDS-U |
12
14.5%
|
16
9.6%
|
28
11.2%
|
| MDS associated with isolated del 5Q |
0
0%
|
0
0%
|
0
0%
|
| Prior MDS Therapy (Number) [Number] | |||
| No |
70
84.3%
|
133
79.6%
|
203
81.2%
|
| Yes |
13
15.7%
|
34
20.4%
|
47
18.8%
|
| Baseline Platelet Counts (10^9/L) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [10^9/L] |
21.5
(13)
|
22.3
(11.5)
|
22.0
(12.0)
|
| International Prognostic Scoring System (IPSS) Total Score (Number) [Number] | |||
| 0 |
23
27.7%
|
40
24%
|
63
25.2%
|
| 0.5 |
38
45.8%
|
86
51.5%
|
124
49.6%
|
| 1 |
20
24.1%
|
34
20.4%
|
54
21.6%
|
| 1.5 |
0
0%
|
1
0.6%
|
1
0.4%
|
| Missing |
2
2.4%
|
6
3.6%
|
8
3.2%
|
Outcome Measures
| Title | Number of Clinically Significant Bleeding Events |
|---|---|
| Description | A clinically significant bleeding event is defined as any bleeding event of grade ≥ 2 per the modified World Health Organization (WHO) bleeding scale: • Grade 0 = no bleeding • Grade 1 = petechia or mucosal or retinal bleeding not requiring intervention • Grade 2 = melena, hematemesis, hematuria, hemoptysis • Grade 3 = bleeding required red cell transfusion • Grade 4 = retinal bleeding with visual impairment • Grade 5 = non-fatal cerebral bleeding • Grade 6 = fatal cerebral bleeding • Grade 7 = fatal non-cerebral bleeding. Bleeding events that continue for more than 7 days were counted as separate events every eighth day. Multiple events that arose from one organ system on one day were collapsed into one single event. Bleeding events with a start date between the first dose date and the last dose date of the test treatment period+7 days are included. |
| Time Frame | Test Treatment Period (Weeks 1-26) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Number [events] |
116
|
178
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Romiplostim |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.13 |
| Comments | ||
| Method | Anderson-Gill model | |
| Comments | Anderson-Gill model using the model-based variance estimate and stratified by the randomization stratification factors | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.83 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim /Placebo | |
| Title | Annualized Rate of Platelet Transfusion Events |
|---|---|
| Description | A discrete platelet transfusion is any number of platelet transfusion administered within a 3-day period. Transfusions administered more than 3 days apart are counted as separate events. Transfusion given in the absence of any bleeding, when platelet count is >10x10^9/L, is not counted as a platelet transfusion event. Events with start date between the first dose date and the last dose date of the test treatment period +7 days are included. Exposure adjusted event rate per 100 patient-years = (events / patient-years * 100). Patient Year = total patient years of exposure to investigational product during 26 weeks test treatment period. |
| Time Frame | Test Treatment Period (Weeks 1-26) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Mean (95% Confidence Interval) [events per 100 patient-years] |
1013.5
|
748.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Romiplostim |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Poisson regression model | |
| Comments | Poisson regression model with treatment and stratification factors as covariates. | |
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.766 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 0.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim /Placebo | |
| Title | Annualized Rate of Overall Bleeding Events |
|---|---|
| Description | The time from first dose of study drug to the last dose of 26-week test treatment period. A bleeding event is defined as any bleeding event reported during the test treatment period. Bleeding events that continue for more than 7 days are counted as separate events every eighth day. Multiple events that arose from one organ system on one day are collapsed into one single event. Exposure adjusted event rate per 100 patient-years = events / patient-year * 100). |
| Time Frame | Test Treatment Period (Weeks 1-26) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Mean (95% Confidence Interval) [events per 100 patient-years] |
3786.4
|
3459.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Romiplostim |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.026 |
| Comments | ||
| Method | Poisson regression model | |
| Comments | Poisson regression model with treatment and stratification factors as covariates. | |
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.922 | |
| Confidence Interval |
(2-Sided) 95% 0.86 to 0.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim /Placebo | |
| Title | Annualized Rate of Total Platelet Transfusion Units |
|---|---|
| Description | The time from first dose of study drug to the last dose of 26-week test treatment period. A unit of platelets is defined as a single pack of pooled platelet-rich plasma comprised of 6 to 8 individual platelet concentrate packs (200 to 400 mL), a single pack of pooled buffy-coat concentrate, or 1 apheresis (single donor) concentrate. Exposure adjusted event rate per 100 patient-years = events / patient-years * 100. |
| Time Frame | Test Treatment Period (Weeks 1-26) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized subjects |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Mean (95% Confidence Interval) [units per 100 patient-years] |
3120.2
|
2221.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Romiplostim |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Poisson Regression model | |
| Comments | Poisson regression model with treatment and stratification factors as covariates | |
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.739 | |
| Confidence Interval |
(2-Sided) 95% 0.68 to 0.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim /Placebo | |
| Title | Number of Participants With Platelet Hematologic Improvement (HI-P) |
|---|---|
| Description | Platelet Hematologic Improvemen defined by the international working group (IWG) as: an absolute increase in platelet count of ≥ 30 x 10^9/L for a patient starting with a platelet count of ≥ 20 x 10^9/L or an increase in platelet count from < 20 x 10^9/L to ≥ 20 x 10^9/L and by at least 100% in a patient that started with a platelet count < 20 x 10^9/L. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint. |
| Time Frame | Test Treatment Period (Weeks 1-26) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Number [Participants] |
3
3.6%
|
61
36.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Romiplostim |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test controlling for stratification factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 15.6 | |
| Confidence Interval |
(2-Sided) 95% 4.7 to 51.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim /Placebo | |
| Title | Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions |
|---|---|
| Description | Duration for participants who did not report HI-P during the period is 0. A platelet hematologic improvement (HI-P) is defined by an MDS International Working criteria as patients with a baseline platelet count of ≥ 20 x 10^9/L achieving an absolute increase of ≥ 30 x 10^9/L or increasing the platelet count to above 20 x 10^9/L and by at least 100% in patients with a baseline of < 20 x 10^9/L for at least 8 consecutive weeks. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint. The durations of HI-P are cumulative if more than one incidence occurred. Exposure adjusted event rate per 100 patient-weeks = total number of weeks / patient-weeks * 100. |
| Time Frame | Test Treatment Period (Weeks 1-26) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Mean (95% Confidence Interval) [weeks per 100 patient-weeks] |
2.57
|
35.02
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Romiplostim |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.032 |
| Comments | ||
| Method | Poisson regression model | |
| Comments | Poisson regression model with treatment and stratification factors as covariates | |
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.402 | |
| Confidence Interval |
(2-Sided) 95% 1.03 to 1.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim /Placebo | |
| Title | Number of Participants Who Died |
|---|---|
| Description | |
| Time Frame | From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Number [participants] |
17
20.5%
|
30
18%
|
| Title | Time to Death |
|---|---|
| Description | Overall survival was calculated using Kaplan-Meier methods. For patients who discontinued early, additional information from the long term follow-up are added (closest available follow-up information up to 58 weeks). |
| Time Frame | From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Kaplan-Meier Estimate of Survival at Month 12 |
|---|---|
| Description | Overall survival was calculated using Kaplan-Meier methods. |
| Time Frame | Month 12, with a data cut-off date of 20 July 2012. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set includes all randomized patients. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 83 | 167 |
| Number (95% Confidence Interval) [percentage of participants] |
78
94%
|
83
49.7%
|
| Title | Annualized Rate of Patient-reported Bleeding Events |
|---|---|
| Description | The number of bleeding events was obtained from the thrombocytopenia symptoms (Th-symptoms) survey. Patients reported spontaneous bleeding to have occurred 0, 1 or 2, 3 or 4, 5 or 6, or 7 or more times in the past week. The lower threshold of bleeding counts is used for conservative purposes (i.e., the "3" is used for the response option of "3 or 4 times"). Exposure adjusted event rate per 100 patient-years = number of events / patient-year * 100. |
| Time Frame | Test Treatment Period (Weeks 1-26) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Patient Reported Outcomes (PRO) analysis set consists of patients in the full analysis set who also completed the baseline and at least one post-baseline assessment for any PRO measure. |
| Arm/Group Title | Placebo | Romiplostim |
|---|---|---|
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. |
| Measure Participants | 82 | 162 |
| Mean (95% Confidence Interval) [events per 100 patient-years] |
1995
|
1264
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Romiplostim |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Poisson regression model | |
| Comments | Poisson regression model with treatment and stratification factors as covariates | |
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.639 | |
| Confidence Interval |
(2-Sided) 95% 0.57 to 0.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim /Placebo | |
Adverse Events
| Time Frame | 58 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The safety analysis set consisted of 250 patients including 168 in the romiplostim group and 82 in the placebo group. One patient enrolled in the placebo group received 1 dose of romiplostim at week 4 of the extended treatment period. Results for this patient were analyzed as part of the romiplostim group in the Safety Analysis Set. | |||
| Arm/Group Title | Placebo | Romiplostim | ||
| Arm/Group Description | Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. | ||
All Cause Mortality |
||||
| Placebo | Romiplostim | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Romiplostim | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/82 (26.8%) | 67/168 (39.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/82 (2.4%) | 7/168 (4.2%) | ||
| Aplastic anaemia | 1/82 (1.2%) | 0/168 (0%) | ||
| Extramedullary haemopoiesis | 0/82 (0%) | 1/168 (0.6%) | ||
| Febrile neutropenia | 2/82 (2.4%) | 2/168 (1.2%) | ||
| Iron deficiency anaemia | 0/82 (0%) | 1/168 (0.6%) | ||
| Leukocytosis | 0/82 (0%) | 1/168 (0.6%) | ||
| Neutropenia | 0/82 (0%) | 1/168 (0.6%) | ||
| Pancytopenia | 1/82 (1.2%) | 0/168 (0%) | ||
| Splenic infarction | 0/82 (0%) | 2/168 (1.2%) | ||
| Thrombocytopenia | 0/82 (0%) | 6/168 (3.6%) | ||
| Cardiac disorders | ||||
| Angina pectoris | 1/82 (1.2%) | 0/168 (0%) | ||
| Atrial fibrillation | 1/82 (1.2%) | 5/168 (3%) | ||
| Cardiac failure congestive | 1/82 (1.2%) | 0/168 (0%) | ||
| Cardiogenic shock | 1/82 (1.2%) | 0/168 (0%) | ||
| Coronary artery disease | 0/82 (0%) | 1/168 (0.6%) | ||
| Coronary artery stenosis | 1/82 (1.2%) | 0/168 (0%) | ||
| Myocardial infarction | 1/82 (1.2%) | 2/168 (1.2%) | ||
| Eye disorders | ||||
| Retinal detachment | 0/82 (0%) | 1/168 (0.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/82 (0%) | 1/168 (0.6%) | ||
| Abdominal pain upper | 1/82 (1.2%) | 0/168 (0%) | ||
| Diarrhoea | 2/82 (2.4%) | 1/168 (0.6%) | ||
| Gastric ulcer | 0/82 (0%) | 1/168 (0.6%) | ||
| Gastrointestinal haemorrhage | 1/82 (1.2%) | 3/168 (1.8%) | ||
| Gingival bleeding | 1/82 (1.2%) | 1/168 (0.6%) | ||
| Haematemesis | 1/82 (1.2%) | 0/168 (0%) | ||
| Melaena | 0/82 (0%) | 1/168 (0.6%) | ||
| Mesenteric artery thrombosis | 0/82 (0%) | 1/168 (0.6%) | ||
| Mouth haemorrhage | 1/82 (1.2%) | 1/168 (0.6%) | ||
| General disorders | ||||
| Asthenia | 0/82 (0%) | 2/168 (1.2%) | ||
| Fatigue | 0/82 (0%) | 1/168 (0.6%) | ||
| General physical health deterioration | 1/82 (1.2%) | 0/168 (0%) | ||
| Hernia | 0/82 (0%) | 1/168 (0.6%) | ||
| Malaise | 0/82 (0%) | 1/168 (0.6%) | ||
| Multi-organ failure | 0/82 (0%) | 1/168 (0.6%) | ||
| Pyrexia | 1/82 (1.2%) | 7/168 (4.2%) | ||
| Hepatobiliary disorders | ||||
| Acute hepatic failure | 1/82 (1.2%) | 0/168 (0%) | ||
| Hepatic cirrhosis | 0/82 (0%) | 1/168 (0.6%) | ||
| Infections and infestations | ||||
| Anal abscess | 1/82 (1.2%) | 0/168 (0%) | ||
| Bronchitis | 0/82 (0%) | 2/168 (1.2%) | ||
| Bronchopneumonia | 1/82 (1.2%) | 2/168 (1.2%) | ||
| Chronic sinusitis | 0/82 (0%) | 1/168 (0.6%) | ||
| Erysipelas | 0/82 (0%) | 2/168 (1.2%) | ||
| Escherichia sepsis | 1/82 (1.2%) | 0/168 (0%) | ||
| External ear cellulitis | 0/82 (0%) | 1/168 (0.6%) | ||
| Gastroenteritis | 0/82 (0%) | 1/168 (0.6%) | ||
| Gastroenteritis norovirus | 0/82 (0%) | 1/168 (0.6%) | ||
| Gastroenteritis viral | 0/82 (0%) | 1/168 (0.6%) | ||
| Gingival infection | 0/82 (0%) | 1/168 (0.6%) | ||
| Lobar pneumonia | 0/82 (0%) | 1/168 (0.6%) | ||
| Lower respiratory tract infection | 1/82 (1.2%) | 0/168 (0%) | ||
| Neutropenic sepsis | 0/82 (0%) | 2/168 (1.2%) | ||
| Pneumonia | 0/82 (0%) | 8/168 (4.8%) | ||
| Pneumonia viral | 1/82 (1.2%) | 0/168 (0%) | ||
| Pyelonephritis | 0/82 (0%) | 1/168 (0.6%) | ||
| Respiratory tract infection | 1/82 (1.2%) | 0/168 (0%) | ||
| Sepsis | 0/82 (0%) | 3/168 (1.8%) | ||
| Urosepsis | 0/82 (0%) | 1/168 (0.6%) | ||
| Viral pericarditis | 0/82 (0%) | 1/168 (0.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Head injury | 0/82 (0%) | 4/168 (2.4%) | ||
| Joint dislocation | 0/82 (0%) | 1/168 (0.6%) | ||
| Lower limb fracture | 0/82 (0%) | 1/168 (0.6%) | ||
| Overdose | 0/82 (0%) | 1/168 (0.6%) | ||
| Post procedural haemorrhage | 0/82 (0%) | 2/168 (1.2%) | ||
| Procedural complication | 0/82 (0%) | 1/168 (0.6%) | ||
| Spinal compression fracture | 1/82 (1.2%) | 0/168 (0%) | ||
| Subdural haematoma | 0/82 (0%) | 1/168 (0.6%) | ||
| Transfusion reaction | 0/82 (0%) | 1/168 (0.6%) | ||
| Ulna fracture | 1/82 (1.2%) | 0/168 (0%) | ||
| Upper limb fracture | 0/82 (0%) | 1/168 (0.6%) | ||
| Investigations | ||||
| Blast cell count increased | 1/82 (1.2%) | 0/168 (0%) | ||
| Hepatic enzyme increased | 1/82 (1.2%) | 0/168 (0%) | ||
| Myeloblast count increased | 0/82 (0%) | 2/168 (1.2%) | ||
| Oxygen saturation decreased | 1/82 (1.2%) | 0/168 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/82 (1.2%) | 0/168 (0%) | ||
| Diabetes mellitus inadequate control | 0/82 (0%) | 1/168 (0.6%) | ||
| Type 2 diabetes mellitus | 0/82 (0%) | 1/168 (0.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/82 (0%) | 2/168 (1.2%) | ||
| Osteoarthritis | 1/82 (1.2%) | 1/168 (0.6%) | ||
| Osteosclerosis | 0/82 (0%) | 1/168 (0.6%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/82 (1.2%) | 0/168 (0%) | ||
| Colon cancer | 0/82 (0%) | 1/168 (0.6%) | ||
| Lung neoplasm malignant | 0/82 (0%) | 1/168 (0.6%) | ||
| Myelofibrosis | 0/82 (0%) | 1/168 (0.6%) | ||
| Nervous system disorders | ||||
| Cerebral haemorrhage | 2/82 (2.4%) | 0/168 (0%) | ||
| Dizziness | 0/82 (0%) | 2/168 (1.2%) | ||
| Encephalitis | 1/82 (1.2%) | 0/168 (0%) | ||
| Headache | 0/82 (0%) | 1/168 (0.6%) | ||
| Hydrocephalus | 0/82 (0%) | 1/168 (0.6%) | ||
| Subarachnoid haemorrhage | 1/82 (1.2%) | 0/168 (0%) | ||
| Syncope | 0/82 (0%) | 2/168 (1.2%) | ||
| Transient ischaemic attack | 0/82 (0%) | 1/168 (0.6%) | ||
| Wallenberg syndrome | 0/82 (0%) | 1/168 (0.6%) | ||
| Renal and urinary disorders | ||||
| Acute prerenal failure | 0/82 (0%) | 1/168 (0.6%) | ||
| Haematuria | 1/82 (1.2%) | 1/168 (0.6%) | ||
| Obstructive uropathy | 0/82 (0%) | 1/168 (0.6%) | ||
| Reproductive system and breast disorders | ||||
| Vaginal haemorrhage | 1/82 (1.2%) | 0/168 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 0/82 (0%) | 1/168 (0.6%) | ||
| Dyspnoea | 2/82 (2.4%) | 1/168 (0.6%) | ||
| Epistaxis | 1/82 (1.2%) | 4/168 (2.4%) | ||
| Respiratory distress | 0/82 (0%) | 1/168 (0.6%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 0/82 (0%) | 1/168 (0.6%) | ||
| Haemorrhage | 1/82 (1.2%) | 0/168 (0%) | ||
| Hypertensive crisis | 0/82 (0%) | 1/168 (0.6%) | ||
| Hypotension | 0/82 (0%) | 1/168 (0.6%) | ||
| Shock haemorrhagic | 1/82 (1.2%) | 0/168 (0%) | ||
| Thrombosis | 0/82 (0%) | 1/168 (0.6%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Romiplostim | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 74/82 (90.2%) | 146/168 (86.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 7/82 (8.5%) | 16/168 (9.5%) | ||
| Eye disorders | ||||
| Conjunctival haemorrhage | 5/82 (6.1%) | 9/168 (5.4%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 5/82 (6.1%) | 10/168 (6%) | ||
| Constipation | 6/82 (7.3%) | 9/168 (5.4%) | ||
| Diarrhoea | 10/82 (12.2%) | 23/168 (13.7%) | ||
| Gingival bleeding | 14/82 (17.1%) | 33/168 (19.6%) | ||
| Mouth haemorrhage | 8/82 (9.8%) | 21/168 (12.5%) | ||
| Nausea | 7/82 (8.5%) | 27/168 (16.1%) | ||
| Vomiting | 5/82 (6.1%) | 8/168 (4.8%) | ||
| General disorders | ||||
| Asthenia | 6/82 (7.3%) | 22/168 (13.1%) | ||
| Fatigue | 7/82 (8.5%) | 24/168 (14.3%) | ||
| Injection site haematoma | 11/82 (13.4%) | 12/168 (7.1%) | ||
| Oedema peripheral | 7/82 (8.5%) | 26/168 (15.5%) | ||
| Pyrexia | 12/82 (14.6%) | 17/168 (10.1%) | ||
| Vessel puncture site haematoma | 6/82 (7.3%) | 6/168 (3.6%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 8/82 (9.8%) | 14/168 (8.3%) | ||
| Oral herpes | 5/82 (6.1%) | 7/168 (4.2%) | ||
| Upper respiratory tract infection | 6/82 (7.3%) | 6/168 (3.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 10/82 (12.2%) | 41/168 (24.4%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 2/82 (2.4%) | 17/168 (10.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/82 (3.7%) | 20/168 (11.9%) | ||
| Back pain | 6/82 (7.3%) | 15/168 (8.9%) | ||
| Bone pain | 1/82 (1.2%) | 9/168 (5.4%) | ||
| Musculoskeletal pain | 3/82 (3.7%) | 15/168 (8.9%) | ||
| Myalgia | 5/82 (6.1%) | 4/168 (2.4%) | ||
| Pain in extremity | 5/82 (6.1%) | 17/168 (10.1%) | ||
| Nervous system disorders | ||||
| Dizziness | 6/82 (7.3%) | 16/168 (9.5%) | ||
| Headache | 10/82 (12.2%) | 29/168 (17.3%) | ||
| Syncope | 5/82 (6.1%) | 0/168 (0%) | ||
| Psychiatric disorders | ||||
| Insomnia | 2/82 (2.4%) | 13/168 (7.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 10/82 (12.2%) | 25/168 (14.9%) | ||
| Dyspnoea | 4/82 (4.9%) | 13/168 (7.7%) | ||
| Epistaxis | 32/82 (39%) | 66/168 (39.3%) | ||
| Oropharyngeal pain | 4/82 (4.9%) | 9/168 (5.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Blood blister | 11/82 (13.4%) | 25/168 (14.9%) | ||
| Ecchymosis | 8/82 (9.8%) | 20/168 (11.9%) | ||
| Petechiae | 20/82 (24.4%) | 42/168 (25%) | ||
| Pruritus | 6/82 (7.3%) | 10/168 (6%) | ||
| Rash | 10/82 (12.2%) | 12/168 (7.1%) | ||
| Vascular disorders | ||||
| Capillary fragility | 5/82 (6.1%) | 0/168 (0%) | ||
| Haematoma | 33/82 (40.2%) | 58/168 (34.5%) | ||
| Haemorrhage | 15/82 (18.3%) | 24/168 (14.3%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial resul
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00614523
Other Study ID Numbers:
- 20060198
First Posted:
Feb 13, 2008
Last Update Posted:
Jan 18, 2020
Last Verified:
Jan 1, 2020