Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00321711
Collaborator
(none)
69
5
36.6
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the appropriate dose and schedule, will result in reduction in the incidence of clinically significant thrombocytopenic events in low or intermediate risk MDS subjects receiving hypomethylating agents.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
69 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 (AMG 531) Treatment of Subjects With Low or Intermediate Risk Myelodysplastic Syndrome (MDS) Receiving Hypomethylating Agents
Actual Study Start Date
:
Oct 1, 2006
Actual Primary Completion Date
:
Oct 19, 2009
Actual Study Completion Date
:
Oct 19, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Dose level 1 500 AMG 531 (Part A - azacitidine) 500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles |
Biological: AMG 531 (Romiplostim)
AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization.
Drug: Azacitidine
hypomethylating agent
|
| Active Comparator: Dose level 1 750 AMG 531 (Part B - decitabine) 750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles |
Biological: AMG 531 (Romiplostim)
AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization.
Drug: Decitabine
hypomethylating agent
|
| Active Comparator: Dose level 2 750 AMG 531 (Part A - azacitidine) 750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles |
Biological: AMG 531 (Romiplostim)
AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization.
Drug: Azacitidine
hypomethylating agent
|
| Placebo Comparator: Placebo (Part A - azacitidine) Placebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles |
Drug: Placebo
Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period.
Drug: Azacitidine
hypomethylating agent
|
| Placebo Comparator: Placebo (Part B - decitabine) Placebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles |
Drug: Placebo
Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period.
Drug: Decitabine
hypomethylating agent
|
Outcome Measures
Primary Outcome Measures
- Occurrence of a Clinically Significant Thrombocytopenic Event [Treatment period (up to 20 weeks)]
Occurrence of a clinically significant thrombocytopenic event within the participant, defined as any platelet count obtained from day 15 of cycle 1 through the end of the interim follow-up visit that was less than 50 x 10^9/L or receipt of platelet transfusions at any time through the interim follow-up visit.
Secondary Outcome Measures
- Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia [Treatment period (up to 20 weeks)]
Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia
- Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period [Treatment period (up to 20 weeks)]
CR = decrease in bone marrow blast (≤5%) and improvement in peripheral blood counts (Hgb ≥ 11 g/dL, platelets ≥ 100x10^9/L, neutrophils ≥ 1x10^9/L, peripheral blasts=0%). PR = improvement in peripheral blood counts plus a decrease in bone marrow blasts ≥50% but not ≤5, or decrease in International Prognostic Scoring System score.
- Platelet Transfusion [Study day 1 through the interim follow-up visit (up to 20 weeks)]
Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria: - Diagnosis of MDS by bone marrow biopsy based on the World Health Organization (WHO) classification - Low, Intermediate-1 or Intermediate-2 risk category MDS using the IPSS (International Prognostic Scoring System) - Planned to receive either azacytidine 75 mg/m2 by subcutaneous administration each day for 7 days or decitabine 20 mg/m2 by intravenous administration each day for 5 days for at least 4 cycles Exclusion
Criteria:
-
Prior exposure to >3 cycles hypomethylating agents
-
Prior history of leukemia or aplastic anemia
-
Prior history of bone marrow transplantation
-
Prior malignancy (other than in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ³ 3 years before randomization
-
Active or uncontrolled infections
-
Unstable angina, congestive heart failure [NYHA (New York Heart Association) > 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) in the past year
-
History of venous thrombosis that currently requires anti-coagulation therapy
-
Received IL-11 within 4 weeks of screening
-
Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication
-
Have previously received any other thrombopoietic growth factor
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
- Greenberg PL, Garcia-Manero G, Moore M, Damon L, Roboz G, Hu K, Yang AS, Franklin J. A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving decitabine. Leuk Lymphoma. 2013 Feb;54(2):321-8. doi: 10.3109/10428194.2012.713477. Epub 2012 Nov 15.
- Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, Garcia-Manero G, Hu K, Franklin JL, Berger DP. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010 Oct 28;116(17):3163-70. doi: 10.1182/blood-2010-03-274753. Epub 2010 Jul 14.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00321711
Other Study ID Numbers:
- 20050232
First Posted:
May 4, 2006
Last Update Posted:
Oct 17, 2018
Last Verified:
Sep 1, 2018
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants in Part A were enrolled from 9 November 2006 through 31 August 2007; participants in Part B were enrolled from 26 March 2008 through 3 November 2008. Participants who enrolled in Part A were not eligible for enrollment in Part B. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Romiplostim (AMG 531) Placebo Plus Azacitidine | Romiplostim (AMG 531) 500 mcg Plus Azacitidine | Romiplostim (AMG 531) 750 mcg Plus Azacitidine | Romiplostim (AMG 531) Placebo Plus Decitabine | Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|---|---|---|
| Arm/Group Description | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 500 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) |
| Period Title: Part A | |||||
| STARTED | 13 | 13 | 14 | 0 | 0 |
| COMPLETED | 8 | 3 | 3 | 0 | 0 |
| NOT COMPLETED | 5 | 10 | 11 | 0 | 0 |
| Period Title: Part A | |||||
| STARTED | 0 | 0 | 0 | 14 | 15 |
| COMPLETED | 0 | 0 | 0 | 8 | 10 |
| NOT COMPLETED | 0 | 0 | 0 | 6 | 5 |
Baseline Characteristics
| Arm/Group Title | Romiplostim (AMG 531) Placebo Plus Azacitidine | Romiplostim (AMG 531) 500 mcg Plus Azacitidine | Romiplostim (AMG 531) 750 mcg Plus Azacitidine | Romiplostim (AMG 531) Placebo Plus Decitabine | Romiplostim (AMG 531) 750 mcg Plus Decitabine | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 500 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) | Total of all reporting groups |
| Overall Participants | 13 | 13 | 14 | 14 | 15 | 69 |
| Age (Years) [Mean (Full Range) ] | ||||||
| Mean (Full Range) [Years] |
67.3
|
71.9
|
71.4
|
70.5
|
68.2
|
69.8
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
6
46.2%
|
3
23.1%
|
7
50%
|
3
21.4%
|
7
46.7%
|
26
37.7%
|
| Male |
7
53.8%
|
10
76.9%
|
7
50%
|
11
78.6%
|
8
53.3%
|
43
62.3%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||||
| White or Caucasian |
13
100%
|
10
76.9%
|
14
100%
|
9
64.3%
|
11
73.3%
|
57
82.6%
|
| Black or African American |
0
0%
|
2
15.4%
|
0
0%
|
1
7.1%
|
1
6.7%
|
4
5.8%
|
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
2
14.3%
|
3
20%
|
5
7.2%
|
| Asian |
0
0%
|
1
7.7%
|
0
0%
|
2
14.3%
|
0
0%
|
3
4.3%
|
Outcome Measures
| Title | Occurrence of a Clinically Significant Thrombocytopenic Event |
|---|---|
| Description | Occurrence of a clinically significant thrombocytopenic event within the participant, defined as any platelet count obtained from day 15 of cycle 1 through the end of the interim follow-up visit that was less than 50 x 10^9/L or receipt of platelet transfusions at any time through the interim follow-up visit. |
| Time Frame | Treatment period (up to 20 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set, composed of all randomized participants |
| Arm/Group Title | Romiplostim (AMG 531) Placebo Plus Azacitidine | Romiplostim (AMG 531) 500 mcg Plus Azacitidine | Romiplostim (AMG 531) 750 mcg Plus Azacitidine | Romiplostim (AMG 531) Placebo Plus Decitabine | Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|---|---|---|
| Arm/Group Description | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 500 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) |
| Measure Participants | 13 | 13 | 14 | 14 | 15 |
| Number [Participants] |
11
84.6%
|
8
61.5%
|
10
71.4%
|
11
78.6%
|
12
80%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Decitabine, Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.032 | |
| Confidence Interval |
() 95% 0.153 to 6.950 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Azacitidine, Romiplostim (AMG 531) 750 mcg Plus Azacitidine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.333 | |
| Confidence Interval |
() 95% 0.028 to 3.926 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Azacitidine, Romiplostim (AMG 531) 500 mcg Plus Azacitidine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.118 | |
| Confidence Interval |
() 95% 0.007 to 1.882 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted by the stratification factor | |
| Title | Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia |
|---|---|
| Description | Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia |
| Time Frame | Treatment period (up to 20 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set, composed of all randomized participants |
| Arm/Group Title | Romiplostim (AMG 531) Placebo Plus Azacitidine | Romiplostim (AMG 531) 500 mcg Plus Azacitidine | Romiplostim (AMG 531) 750 mcg Plus Azacitidine | Romiplostim (AMG 531) Placebo Plus Decitabine | Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|---|---|---|
| Arm/Group Description | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 500 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) |
| Measure Participants | 13 | 13 | 14 | 14 | 15 |
| Number [Participants] |
1
7.7%
|
1
7.7%
|
0
0%
|
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Azacitidine, Romiplostim (AMG 531) 500 mcg Plus Azacitidine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.000 | |
| Confidence Interval |
() 95% 0.063 to 15.988 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim/placebo | |
| Title | Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period |
|---|---|
| Description | CR = decrease in bone marrow blast (≤5%) and improvement in peripheral blood counts (Hgb ≥ 11 g/dL, platelets ≥ 100x10^9/L, neutrophils ≥ 1x10^9/L, peripheral blasts=0%). PR = improvement in peripheral blood counts plus a decrease in bone marrow blasts ≥50% but not ≤5, or decrease in International Prognostic Scoring System score. |
| Time Frame | Treatment period (up to 20 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set, composed of all randomized participants |
| Arm/Group Title | Romiplostim (AMG 531) Placebo Plus Azacitidine | Romiplostim (AMG 531) 500 mcg Plus Azacitidine | Romiplostim (AMG 531) 750 mcg Plus Azacitidine | Romiplostim (AMG 531) Placebo Plus Decitabine | Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|---|---|---|
| Arm/Group Description | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 500 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) |
| Measure Participants | 13 | 13 | 14 | 14 | 15 |
| Number [Participants] |
2
15.4%
|
1
7.7%
|
1
7.1%
|
3
21.4%
|
5
33.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Decitabine, Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.827 | |
| Confidence Interval |
() 95% 0.347 to 9.618 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim/placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Azacitidine, Romiplostim (AMG 531) 750 mcg Plus Azacitidine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.445 | |
| Confidence Interval |
() 95% 0.037 to 5.325 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim/placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Azacitidine, Romiplostim (AMG 531) 500 mcg Plus Azacitidine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.444 | |
| Confidence Interval |
() 95% 0.032 to 6.080 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim/placebo | |
| Title | Platelet Transfusion |
|---|---|
| Description | Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks) |
| Time Frame | Study day 1 through the interim follow-up visit (up to 20 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set, composed of all randomized participants |
| Arm/Group Title | Romiplostim (AMG 531) Placebo Plus Azacitidine | Romiplostim (AMG 531) 500 mcg Plus Azacitidine | Romiplostim (AMG 531) 750 mcg Plus Azacitidine | Romiplostim (AMG 531) Placebo Plus Decitabine | Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|---|---|---|
| Arm/Group Description | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 500 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A) | Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) | 750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 20 mg/m^2 decitabine daily for 5 days during each of four 28-day cycles (Part B) |
| Measure Participants | 13 | 13 | 14 | 14 | 15 |
| Number [Participants] |
9
69.2%
|
6
46.2%
|
5
35.7%
|
8
57.1%
|
7
46.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Azacitidine, Romiplostim (AMG 531) 750 mcg Plus Azacitidine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in incidence rate |
| Estimated Value | -33.5 | |
| Confidence Interval |
() 95% -69.0 to 2.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Romiplostim - placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Decitabine, Romiplostim (AMG 531) 750 mcg Plus Decitabine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.315 | |
| Confidence Interval |
() 95% 0.029 to 3.412 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Romiplostim (AMG 531) Placebo Plus Azacitidine, Romiplostim (AMG 531) 500 mcg Plus Azacitidine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.211 | |
| Confidence Interval |
() 95% 0.021 to 2.082 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Up to 20 weeks | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. | |||||||||
| Arm/Group Title | Part A Placebo | Part A Romiplostim 500 µg | Part A Romiplostim 750 µg | Part B Placebo | Part B Romiplostim 750 µg | |||||
| Arm/Group Description | ||||||||||
All Cause Mortality |
||||||||||
| Part A Placebo | Part A Romiplostim 500 µg | Part A Romiplostim 750 µg | Part B Placebo | Part B Romiplostim 750 µg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Part A Placebo | Part A Romiplostim 500 µg | Part A Romiplostim 750 µg | Part B Placebo | Part B Romiplostim 750 µg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/13 (69.2%) | 4/13 (30.8%) | 10/14 (71.4%) | 8/14 (57.1%) | 8/15 (53.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 1/13 (7.7%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Febrile neutropenia | 3/13 (23.1%) | 1/13 (7.7%) | 1/14 (7.1%) | 3/14 (21.4%) | 4/15 (26.7%) | |||||
| Pancytopenia | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Atrial flutter | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Sick sinus syndrome | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Anal fissure | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Caecitis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Constipation | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Gastrooesophageal reflux disease | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Haemorrhoidal haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Nausea | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Stomatitis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Vomiting | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| General disorders | ||||||||||
| Asthenia | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Chest pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Inflammation | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pain | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pyrexia | 2/13 (15.4%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 2/15 (13.3%) | |||||
| Hepatobiliary disorders | ||||||||||
| Hyperbilirubinaemia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Immune system disorders | ||||||||||
| Hypersensitivity | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Infections and infestations | ||||||||||
| Appendicitis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Arthritis bacterial | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Bronchopulmonary aspergillosis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Diverticulitis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Endocarditis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Escherichia sepsis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Gastroenteritis | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Implant site infection | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Infection | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Neutropenic sepsis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Pneumonia | 1/13 (7.7%) | 0/13 (0%) | 2/14 (14.3%) | 2/14 (14.3%) | 2/15 (13.3%) | |||||
| Pneumonia fungal | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Sepsis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Staphylococcal infection | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Staphylococcal sepsis | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Subcutaneous abscess | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Urinary tract infection | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 2/15 (13.3%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Femoral neck fracture | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Transfusion reaction | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Aspartate aminotransferase increased | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Blood alkaline phosphatase increased | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Failure to thrive | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Myelofibrosis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Nervous system disorders | ||||||||||
| Convulsion | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Dysarthria | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Haemorrhage intracranial | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Neuralgia | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Somnolence | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Syncope | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Disorientation | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Mental status changes | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Renal failure | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Renal failure acute | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 1/13 (7.7%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Dyspnoea exertional | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Epistaxis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Pleural effusion | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Pulmonary artery thrombosis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Pulmonary haemorrhage | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Erythema nodosum | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Vascular disorders | ||||||||||
| Haematoma | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hypotension | 0/13 (0%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Orthostatic hypotension | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Part A Placebo | Part A Romiplostim 500 µg | Part A Romiplostim 750 µg | Part B Placebo | Part B Romiplostim 750 µg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/13 (84.6%) | 13/13 (100%) | 14/14 (100%) | 14/14 (100%) | 14/15 (93.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 3/13 (23.1%) | 1/13 (7.7%) | 2/14 (14.3%) | 4/14 (28.6%) | 2/15 (13.3%) | |||||
| Anaemia haemolytic autoimmune | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Bone marrow disorder | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Febrile neutropenia | 2/13 (15.4%) | 0/13 (0%) | 0/14 (0%) | 2/14 (14.3%) | 1/15 (6.7%) | |||||
| Haemolytic anaemia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Leukocytosis | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Leukopenia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 2/15 (13.3%) | |||||
| Lymphadenopathy | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Neutropenia | 4/13 (30.8%) | 4/13 (30.8%) | 2/14 (14.3%) | 9/14 (64.3%) | 4/15 (26.7%) | |||||
| Pancytopenia | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Thrombocytopenia | 4/13 (30.8%) | 0/13 (0%) | 0/14 (0%) | 3/14 (21.4%) | 2/15 (13.3%) | |||||
| Thrombocytopenic purpura | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Thrombocytosis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Cardiac disorders | ||||||||||
| Atrial flutter | 0/13 (0%) | 2/13 (15.4%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Bradycardia | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Left ventricular dysfunction | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Left ventricular hypertrophy | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Sinus tachycardia | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Tachycardia | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear congestion | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Ear pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Eye disorders | ||||||||||
| Abnormal sensation in eye | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Eye pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Eyelid oedema | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Ocular hyperaemia | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Abdominal distension | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Abdominal pain | 2/13 (15.4%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Abdominal pain upper | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Anal pruritus | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Aphthous stomatitis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Constipation | 5/13 (38.5%) | 7/13 (53.8%) | 7/14 (50%) | 5/14 (35.7%) | 4/15 (26.7%) | |||||
| Diarrhoea | 1/13 (7.7%) | 4/13 (30.8%) | 6/14 (42.9%) | 5/14 (35.7%) | 3/15 (20%) | |||||
| Dry mouth | 1/13 (7.7%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Dyspepsia | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Faecal incontinence | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Flatulence | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Gastrointestinal haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Gastrointestinal oedema | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Gastrooesophageal reflux disease | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Gingival bleeding | 1/13 (7.7%) | 1/13 (7.7%) | 0/14 (0%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Gingival erythema | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Gingival pain | 1/13 (7.7%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Gingival swelling | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Gingivitis | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Glossodynia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Haematemesis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Haematochezia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Haemorrhoidal haemorrhage | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Haemorrhoids | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 2/15 (13.3%) | |||||
| Melaena | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Mouth haemorrhage | 1/13 (7.7%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Mouth ulceration | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Nausea | 6/13 (46.2%) | 4/13 (30.8%) | 6/14 (42.9%) | 6/14 (42.9%) | 5/15 (33.3%) | |||||
| Odynophagia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Oral pain | 0/13 (0%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Proctalgia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Rectal haemorrhage | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Stomatitis | 0/13 (0%) | 2/13 (15.4%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Tongue discolouration | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Tongue ulceration | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Tooth socket haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Toothache | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Vomiting | 2/13 (15.4%) | 2/13 (15.4%) | 1/14 (7.1%) | 1/14 (7.1%) | 2/15 (13.3%) | |||||
| General disorders | ||||||||||
| Asthenia | 2/13 (15.4%) | 1/13 (7.7%) | 2/14 (14.3%) | 1/14 (7.1%) | 2/15 (13.3%) | |||||
| Catheter site haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Catheter site inflammation | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Catheter thrombosis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Chest pain | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Chills | 0/13 (0%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 2/15 (13.3%) | |||||
| Cyst | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Fatigue | 5/13 (38.5%) | 4/13 (30.8%) | 2/14 (14.3%) | 3/14 (21.4%) | 2/15 (13.3%) | |||||
| Gait disturbance | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Infusion site haemorrhage | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site discomfort | 0/13 (0%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site erythema | 1/13 (7.7%) | 2/13 (15.4%) | 3/14 (21.4%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site haematoma | 0/13 (0%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site haemorrhage | 1/13 (7.7%) | 2/13 (15.4%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site irritation | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site pain | 2/13 (15.4%) | 2/13 (15.4%) | 4/14 (28.6%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site pruritus | 1/13 (7.7%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site rash | 0/13 (0%) | 2/13 (15.4%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site reaction | 0/13 (0%) | 1/13 (7.7%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Injection site swelling | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Malaise | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Mucosal inflammation | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Non-cardiac chest pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Oedema peripheral | 4/13 (30.8%) | 2/13 (15.4%) | 2/14 (14.3%) | 3/14 (21.4%) | 3/15 (20%) | |||||
| Pain | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Pyrexia | 1/13 (7.7%) | 0/13 (0%) | 3/14 (21.4%) | 4/14 (28.6%) | 3/15 (20%) | |||||
| Ulcer haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholelithiasis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Hepatic cyst | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hepatomegaly | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Immune system disorders | ||||||||||
| Drug hypersensitivity | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hypersensitivity | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Infections and infestations | ||||||||||
| Bacterial infection | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Bronchitis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Candidiasis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Cellulitis | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Cystitis | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Furuncle | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Infection | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Localised infection | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Nasopharyngitis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 3/15 (20%) | |||||
| Oral candidiasis | 1/13 (7.7%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Oral fungal infection | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Oral herpes | 1/13 (7.7%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Parotitis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Perirectal abscess | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pharyngeal abscess | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pharyngitis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Pneumonia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Sepsis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Sinusitis | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Upper respiratory tract infection | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 4/14 (28.6%) | 0/15 (0%) | |||||
| Urinary tract infection | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 2/15 (13.3%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Compression fracture | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Contusion | 3/13 (23.1%) | 3/13 (23.1%) | 2/14 (14.3%) | 2/14 (14.3%) | 2/15 (13.3%) | |||||
| Excoriation | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Eye injury | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Fall | 0/13 (0%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Incision site pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Scratch | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Skin laceration | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 3/14 (21.4%) | 0/15 (0%) | |||||
| Spinal compression fracture | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Transfusion reaction | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Wound | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Investigations | ||||||||||
| Blood creatinine increased | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Blood magnesium decreased | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Blood pressure increased | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Cardiac murmur | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Heart sounds abnormal | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Platelet count decreased | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Pulmonary arterial pressure increased | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Reticulin increased | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Weight decreased | 0/13 (0%) | 2/13 (15.4%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 0/13 (0%) | 3/13 (23.1%) | 5/14 (35.7%) | 2/14 (14.3%) | 2/15 (13.3%) | |||||
| Dehydration | 2/13 (15.4%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Fluid retention | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Gout | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hypercholesterolaemia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Hyperglycaemia | 1/13 (7.7%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hyperkalaemia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Hypocalcaemia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Hypokalaemia | 2/13 (15.4%) | 0/13 (0%) | 1/14 (7.1%) | 2/14 (14.3%) | 2/15 (13.3%) | |||||
| Hypomagnesaemia | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Hypophosphataemia | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Iron deficiency | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Iron overload | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 1/13 (7.7%) | 2/13 (15.4%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Arthritis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Back pain | 0/13 (0%) | 2/13 (15.4%) | 3/14 (21.4%) | 3/14 (21.4%) | 0/15 (0%) | |||||
| Bone pain | 1/13 (7.7%) | 1/13 (7.7%) | 1/14 (7.1%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Bursitis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Flank pain | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Groin pain | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Joint stiffness | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Joint swelling | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Muscle fatigue | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Muscle haemorrhage | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Muscle spasms | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Muscle swelling | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Muscular weakness | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Musculoskeletal chest pain | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Musculoskeletal pain | 1/13 (7.7%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Myalgia | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Neck pain | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pain in extremity | 1/13 (7.7%) | 2/13 (15.4%) | 5/14 (35.7%) | 1/14 (7.1%) | 3/15 (20%) | |||||
| Pain in jaw | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Trismus | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Hepatic neoplasm | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Lipoma | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Nervous system disorders | ||||||||||
| Balance disorder | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Cerebral ischaemia | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Dizziness | 1/13 (7.7%) | 2/13 (15.4%) | 4/14 (28.6%) | 3/14 (21.4%) | 2/15 (13.3%) | |||||
| Dysgeusia | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Headache | 2/13 (15.4%) | 2/13 (15.4%) | 1/14 (7.1%) | 1/14 (7.1%) | 2/15 (13.3%) | |||||
| Hypersomnia | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Hypoaesthesia | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Lethargy | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Memory impairment | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Mental impairment | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Migraine with aura | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Neuropathy peripheral | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Paraesthesia | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Peripheral sensory neuropathy | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Presyncope | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Tremor | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 1/13 (7.7%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 2/15 (13.3%) | |||||
| Confusional state | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Depression | 1/13 (7.7%) | 2/13 (15.4%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Insomnia | 2/13 (15.4%) | 2/13 (15.4%) | 0/14 (0%) | 4/14 (28.6%) | 4/15 (26.7%) | |||||
| Mental status changes | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Nervousness | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Pollakiuria | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Renal failure | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Renal failure acute | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Urinary retention | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Breast mass | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Breast pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Penile discharge | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Perineal pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Scrotal erythema | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Scrotal swelling | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Vulvovaginal pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 2/13 (15.4%) | 4/13 (30.8%) | 1/14 (7.1%) | 2/14 (14.3%) | 1/15 (6.7%) | |||||
| Dyspnoea | 5/13 (38.5%) | 4/13 (30.8%) | 1/14 (7.1%) | 1/14 (7.1%) | 4/15 (26.7%) | |||||
| Dyspnoea exertional | 1/13 (7.7%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Epistaxis | 5/13 (38.5%) | 3/13 (23.1%) | 1/14 (7.1%) | 3/14 (21.4%) | 3/15 (20%) | |||||
| Haemoptysis | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hypoxia | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Nasal congestion | 0/13 (0%) | 2/13 (15.4%) | 0/14 (0%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Oropharyngeal pain | 1/13 (7.7%) | 0/13 (0%) | 1/14 (7.1%) | 3/14 (21.4%) | 0/15 (0%) | |||||
| Pharyngeal haemorrhage | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pleural effusion | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pleuritic pain | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Postnasal drip | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Productive cough | 1/13 (7.7%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Rales | 1/13 (7.7%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Rhinitis allergic | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Rhinorrhoea | 0/13 (0%) | 0/13 (0%) | 2/14 (14.3%) | 0/14 (0%) | 0/15 (0%) | |||||
| Sputum discoloured | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Throat irritation | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 1/13 (7.7%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Blood blister | 3/13 (23.1%) | 0/13 (0%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Decubitus ulcer | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Dermatitis | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Dermatitis acneiform | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Dermatitis allergic | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Dry skin | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Ecchymosis | 1/13 (7.7%) | 4/13 (30.8%) | 1/14 (7.1%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Erythema | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Hyperhidrosis | 0/13 (0%) | 2/13 (15.4%) | 1/14 (7.1%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Night sweats | 2/13 (15.4%) | 1/13 (7.7%) | 1/14 (7.1%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Petechiae | 2/13 (15.4%) | 2/13 (15.4%) | 1/14 (7.1%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Pruritus | 1/13 (7.7%) | 0/13 (0%) | 2/14 (14.3%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Purpura | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Rash | 2/13 (15.4%) | 2/13 (15.4%) | 3/14 (21.4%) | 1/14 (7.1%) | 1/15 (6.7%) | |||||
| Rosacea | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Skin discolouration | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Skin exfoliation | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Skin lesion | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Skin nodule | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Swelling face | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Urticaria | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 1/15 (6.7%) | |||||
| Vasculitic rash | 0/13 (0%) | 0/13 (0%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Surgical and medical procedures | ||||||||||
| Breast lump removal | 0/13 (0%) | 0/13 (0%) | 0/14 (0%) | 1/14 (7.1%) | 0/15 (0%) | |||||
| Vascular disorders | ||||||||||
| Hot flush | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hypertension | 0/13 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | 0/14 (0%) | 0/15 (0%) | |||||
| Hypotension | 1/13 (7.7%) | 1/13 (7.7%) | 4/14 (28.6%) | 2/14 (14.3%) | 0/15 (0%) | |||||
| Orthostatic hypotension | 1/13 (7.7%) | 0/13 (0%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
| Pallor | 0/13 (0%) | 1/13 (7.7%) | 0/14 (0%) | 0/14 (0%) | 0/15 (0%) | |||||
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 results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00321711
Other Study ID Numbers:
- 20050232
First Posted:
May 4, 2006
Last Update Posted:
Oct 17, 2018
Last Verified:
Sep 1, 2018