Determination of Safe Dose of Romiplostim (AMG 531) in Patients With Myelodysplastic Syndromes (MDS)

An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00303472

Enrollment

Registered

2006-03-17

Start date

2006-02-28

Completion date

2008-05-31

Last updated

2013-12-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

MDS, Myelodysplastic Syndromes, Refractory Cytopenias, Thrombocytopenia

Keywords

MDS, Myelodysplastic Syndromes, Refractory Cytopenias, Thrombocytopenia

Brief summary

The purpose of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with low or Intermediate-1 risk MDS. In addition, the study will evaluate the platelet response to romiplostim.

Interventions

DRUGRomiplostim

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of MDS using the World Health Organization classification * Low or Intermediate-1 risk MDS using the International Prognostic Scoring System (IPSS) * The mean of two platelet counts taken during the screening period must be ≤ 50 x 10\^9/L, with no individual count \> 55 x 10\^9/L (The mean platelet counts of 5 subjects enrolled at the maximum tolerated dose (MTD) must be ≤ 20 x 10\^9/L). Standard of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1. * Must be ≥ 18 years of age at the time of obtaining informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening * Adequate Liver Function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert's Disease), alanine aminotransferase (ALT) ≤ 3 times the laboratory normal range, and aspartate aminotransferase (AST) ≤ 3 times the laboratory normal range * A serum creatinine concentration ≤ 2 mg/dL (≤ 176.6 µmol/L) * Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1)

Exclusion criteria

* Currently receiving any treatment for MDS other than transfusions and erythropoietic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1 * Clinically significant bleeding within 2 weeks prior to screening (eg, gastrointestinal (GI) bleeds, intracranial hemorrhage) * Prior malignancy (other than controlled prostate cancer, in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years before screening * Prior history of bone marrow transplantation * Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count \> 1,000/µL) * 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 * Received Anti-Thymocyte Globuline (ATG) within 6 months of screening * Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening * Received interleukin (IL)-11 (oprelvekin) within 4 weeks before screening * Concurrent use of granulocyte growth factors (i.e. granulocyte-colony stimulating factor \[G-CSF; Neupogen, Granocyte\], pegfilgrastim \[Neulasta\], granulocyte macrophage-colony stimulating factor \[GM-CSF; Leukine, Prokine, Sargramostim\]) * Have ever previously received recombinant thrombopoietin (rTPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, or romiplostim * Less than 4 weeks since receipt of any therapeutic drug or device that is not Food and Drug Administration (FDA) approved for any indication * Other investigational procedures are excluded * History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year * History of venous thrombosis that currently requires anti-coagulation therapy * Untreated B12 or folate deficiency * Subject is evidently pregnant (eg, positive human chorionic gonadotropin \[HCG\] test) or is breast feeding * Subject is not using adequate contraceptive precautions * Subject has known hypersensitivity to any recombinant E coli-derived product * Subject previously has enrolled in this study * Subject will not be available for follow-up assessment * Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

Design outcomes

Primary

Measure	Time frame	Description
Part A: Number of Participants With Adverse Events	Treatment period (4 weeks) plus treatment extension (1 year)	The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part A.
Part B: Number of Participants With Adverse Events	Treatment period (8 weeks) plus treatment extension (1 year)	The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part B.

Secondary

Measure	Time frame	Description
Part A: Number of Participants With a Platelet Response Per IWG Criteria	Treatment period (4 weeks) and extension period (52 weeks).	The number of participants with a platelet response according to the modified International Working Group (IWG) criteria. Response was defined as an absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline count ≤ 20 x 10\^9/L, increasing to above 20 x 10\^9/L and by at least 100% during the treatment or extension period and maintained for at least 8 consecutive weeks. Platelet transfusion was not considered a rescue medication but platelet counts ≤72 hours after platelet transfusion were excluded from the analysis.
Part B: Number of Participants With a Platelet Response Per IWG	Treatment period (8 weeks) and extension period (52 weeks).	The number of participants with a platelet response according to the modified International Working Group (IWG) criteria. Response was defined as an absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline count ≤ 20 x 10\^9/L, increasing to above 20 x 10\^9/L and by at least 100% during the treatment or extension period and maintained for at least 8 consecutive weeks. Platelet transfusion was not considered a rescue medication but platelet counts ≤72 hours after platelet transfusion were excluded from the analysis.
Part B: Peak Platelet Count	Treatment Period (8 weeks)	Peak platelet count (10\^9/L) during the treatment period.
Part B: Time to First Platelet Response	Treatment Period (8 weeks) and extension period (52 weeks).	Participants achieving first platelet response according to IWG criteria, by study week. Platelet response was defined as an absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline ≤ 20 x 10\^9/L increasing the platelet count to above 20 x 10\^9/L and by at least 100% for 8 consecutive weeks. Platelet counts obtained within 72 hours of platelet transfusion were not evaluable for platelet response.
Part B: Duration of Platelet Response	Treatment Period (8 weeks) and extension period (52 weeks)	Duration of platelet response per IWG criteria (absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline ≤ 20 x 10\^9/L increasing the platelet count to above 20 x 10\^9/L and by at least 100% for 8 consecutive weeks).
Part B: Week 1 Cmax	Week 1	Maximum observed serum concentration (Cmax) of romiplostim during Week 1
Part A: Number of Participants With a Complete or Major Platelet Response	Treatment Period (4 weeks)	Participants with a complete or major response during the treatment phase. A complete platelet response was defined as a platelet count ≥ 100 x 10\^9/L during the treatment phase. A major platelet response was defined as an increase in absolute platelet count of ≥ 30 x 10\^9/L for patients starting with \> 20 x 10\^9/L platelets, or an increase from ≤ 20 x 10\^9/L to \> 20 x 10\^9/L and by at least 100%. Any participant receiving rescue medication was considered a non-responder. Platelet transfusions were considered rescue medication.
Part B: Week 1 AUC0-4	Week 1	Area under the romiplostim concentration-time curve from time zero to the last time point with quantifiable concentration (AUC0-4) during Week 1
Part B: Week 7 Cmax	Week 7	Maximum observed serum concentration (Cmax) of romiplostim during Week 7.
Part B: Week 7 Ctrough	Week 7	Measured romiplostim concentration at the end of the Week 7 dosing interval (Ctrough)
Part B: Week 7 AUC0-4	Week 7	Area under the romiplostim concentration-time curve from time zero to the last time point with quantifiable concentration (AUC0-4) during Week 7.
Part B: Week 1 Tmax	Week 1	Time at which the maximum concentration of romiplostum was observed after subcutaneous administration during Week 1
Part B: Week 7 Tmax	Week 7	Time at which the maximum concentration of romiplostum was observed after subcutaneous administration during Week 7
Part B: Week 1 Ctrough	Week 1	Measured romiplostim concentration at the end of the week 1 dosing interval (Ctrough)
Part B: Number of Participants With a Complete or Major Platelet Response	Treatment Period (8 weeks)	Participants with a complete or major response during the treatment phase. A complete platelet response was defined as a platelet count ≥ 100 x 10\^9/L during the treatment phase. A major platelet response was defined as an increase in absolute platelet count of ≥ 30 x 10\^9/L for patients starting with \> 20 x 10\^9/L platelets, or an increase from ≤ 20 x 10\^9/L to \> 20 x 10\^9/L and by at least 100%. Any participant receiving rescue medication was considered a non-responder. Platelet transfusions were considered rescue medication.

Participant flow

Recruitment details

First Subject Enrolled: 15-Feb-2006 Last Subject Enrolled: 29-Feb-2008

Pre-assignment details

The study had 3 parts: Part A (4 weeks), Part B (8 weeks), and a treatment extension phase (up to 1 year). Subjects could participate in either Part A or Part B, and then could choose to enter the treatment extension phase. Subjects participating in Part A were not eligible for participation in Part B.

Participants by arm

Arm	Count
Part A: 300 µg Romiplostim Cohort 1 in Part A, participants received romiplostim 300 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.	6
Part A: 700 µg Romiplostim Cohort 2 in Part A, participants received romiplostim 700 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.	11
Part A: 1000 µg Romiplostim Cohort 3 in Part A, participants received romiplostim 1000 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.	11
Part A: 1500 µg Romiplostim Cohort 4 in Part A, participants received romiplostim 1500 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.	16
Part B: 750 µg Romiplostim SC QW Part B participants received romiplostim 750 µg subcutaneously (SC) once weekly (QW) for 8 weeks. Participants who completed Part B could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.	11
Part B: 750 µg Romiplostim SC Q2W Part B participants received romiplostim 750 µg subcutaneously every two weeks (Q2W) for 8 weeks. Participants who completed Part B could continue to receive injections of romiplostim for up to 1 year in the extension treatment phase.	12
Part B: 750 µg Romiplostim IV Q2W Part B participants received romiplostim 750 µg intravenously (IV) once every two weeks for 8 weeks. Participants who completed Part B could continue to receive romiplostim for up to 1 year in the extension treatment phase.	5
Total	72

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006
Treatment Extension (Optional)	Adverse Event	1	0	1	0	0	0	0
Treatment Extension (Optional)	Death	2	0	1	0	0	0	0
Treatment Extension (Optional)	Disease Progression (to AML)	1	0	0	0	0	1	0
Treatment Extension (Optional)	Lost to Follow-up	0	0	0	1	0	0	0
Treatment Extension (Optional)	Other	0	2	4	2	1	0	0
Treatment Extension (Optional)	Physician Decision	0	4	2	3	2	0	0
Treatment Extension (Optional)	Withdrawal by Subject	1	0	1	2	1	0	0
Treatment Period	Adverse Event	0	0	0	0	1	0	0
Treatment Period	Death	0	0	0	1	0	0	1
Treatment Period	Disease Progression (to AML)	0	0	0	0	1	0	0
Treatment Period	Other	0	0	0	0	1	0	1
Treatment Period	Withdrawal by Subject	0	0	0	1	0	1	0

Baseline characteristics

Characteristic	Part A: 700 µg Romiplostim	Part A: 300 µg Romiplostim	Part A: 1000 µg Romiplostim	Part A: 1500 µg Romiplostim	Part B: 750 µg Romiplostim SC QW	Part B: 750 µg Romiplostim SC Q2W	Part B: 750 µg Romiplostim IV Q2W	Total
Age, Continuous	68.2 Years STANDARD_DEVIATION 10.2	77.5 Years STANDARD_DEVIATION 3.3	70.9 Years STANDARD_DEVIATION 14.2	68.9 Years STANDARD_DEVIATION 13.8	69.4 Years STANDARD_DEVIATION 6.3	72.1 Years STANDARD_DEVIATION 9.9	72.2 Years STANDARD_DEVIATION 4.3	70.7 Years STANDARD_DEVIATION 10.6
Race/Ethnicity, Customized Aborigine	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Japanese	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized White or Caucasian	11 Participants	5 Participants	9 Participants	14 Participants	10 Participants	10 Participants	4 Participants	63 Participants
Sex: Female, Male Female	5 Participants	0 Participants	2 Participants	5 Participants	2 Participants	3 Participants	1 Participants	18 Participants
Sex: Female, Male Male	6 Participants	6 Participants	9 Participants	11 Participants	9 Participants	9 Participants	4 Participants	54 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	6 / 6	11 / 11	11 / 11	15 / 16	10 / 11	10 / 12	4 / 5
serious Total, serious adverse events	2 / 6	3 / 11	2 / 11	10 / 16	1 / 11	2 / 12	2 / 5

Outcome results

Primary

Part A: Number of Participants With Adverse Events

The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part A.

Time frame: Treatment period (4 weeks) plus treatment extension (1 year)

Population: All participants who received at least one dose of study medication

Arm	Measure	Value (NUMBER)
Part A: 300 µg Romiplostim	Part A: Number of Participants With Adverse Events	6 Participants
Part A: 700 µg Romiplostim	Part A: Number of Participants With Adverse Events	11 Participants
Part A: 1000 µg Romiplostim	Part A: Number of Participants With Adverse Events	11 Participants
Part A: 1500 µg Romiplostim	Part A: Number of Participants With Adverse Events	15 Participants

Primary

Part B: Number of Participants With Adverse Events

The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part B.

Time frame: Treatment period (8 weeks) plus treatment extension (1 year)

Population: All participants who received at least one dose of study medication

Arm	Measure	Value (NUMBER)
Part A: 300 µg Romiplostim	Part B: Number of Participants With Adverse Events	10 Participants
Part A: 700 µg Romiplostim	Part B: Number of Participants With Adverse Events	11 Participants
Part A: 1000 µg Romiplostim	Part B: Number of Participants With Adverse Events	5 Participants

Secondary

Part A: Number of Participants With a Complete or Major Platelet Response

Participants with a complete or major response during the treatment phase. A complete platelet response was defined as a platelet count ≥ 100 x 10\^9/L during the treatment phase. A major platelet response was defined as an increase in absolute platelet count of ≥ 30 x 10\^9/L for patients starting with \> 20 x 10\^9/L platelets, or an increase from ≤ 20 x 10\^9/L to \> 20 x 10\^9/L and by at least 100%. Any participant receiving rescue medication was considered a non-responder. Platelet transfusions were considered rescue medication.

Time frame: Treatment Period (4 weeks)

Population: Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase.

Arm	Measure	Value (NUMBER)
Part A: 300 µg Romiplostim	Part A: Number of Participants With a Complete or Major Platelet Response	3 Participants
Part A: 700 µg Romiplostim	Part A: Number of Participants With a Complete or Major Platelet Response	5 Participants
Part A: 1000 µg Romiplostim	Part A: Number of Participants With a Complete or Major Platelet Response	4 Participants
Part A: 1500 µg Romiplostim	Part A: Number of Participants With a Complete or Major Platelet Response	8 Participants

Secondary

Part A: Number of Participants With a Platelet Response Per IWG Criteria

The number of participants with a platelet response according to the modified International Working Group (IWG) criteria. Response was defined as an absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline count ≤ 20 x 10\^9/L, increasing to above 20 x 10\^9/L and by at least 100% during the treatment or extension period and maintained for at least 8 consecutive weeks. Platelet transfusion was not considered a rescue medication but platelet counts ≤72 hours after platelet transfusion were excluded from the analysis.

Time frame: Treatment period (4 weeks) and extension period (52 weeks).

Population: Subset of Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase, who entered the treatment extension.

Arm	Measure	Value (NUMBER)
Part A: 300 µg Romiplostim	Part A: Number of Participants With a Platelet Response Per IWG Criteria	3 Participants
Part A: 700 µg Romiplostim	Part A: Number of Participants With a Platelet Response Per IWG Criteria	6 Participants
Part A: 1000 µg Romiplostim	Part A: Number of Participants With a Platelet Response Per IWG Criteria	4 Participants
Part A: 1500 µg Romiplostim	Part A: Number of Participants With a Platelet Response Per IWG Criteria	6 Participants

Secondary

Part B: Duration of Platelet Response

Duration of platelet response per IWG criteria (absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline ≤ 20 x 10\^9/L increasing the platelet count to above 20 x 10\^9/L and by at least 100% for 8 consecutive weeks).

Time frame: Treatment Period (8 weeks) and extension period (52 weeks)

Population: Subset of Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase, who had a platelet response

Arm	Measure	Value (MEDIAN)
Part A: 300 µg Romiplostim	Part B: Duration of Platelet Response	19.5 Weeks
Part A: 700 µg Romiplostim	Part B: Duration of Platelet Response	9.0 Weeks
Part A: 1000 µg Romiplostim	Part B: Duration of Platelet Response	9.0 Weeks

Secondary

Part B: Number of Participants With a Complete or Major Platelet Response

Time frame: Treatment Period (8 weeks)

Population: Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase.

Arm	Measure	Value (NUMBER)
Part A: 300 µg Romiplostim	Part B: Number of Participants With a Complete or Major Platelet Response	5 Participants
Part A: 700 µg Romiplostim	Part B: Number of Participants With a Complete or Major Platelet Response	8 Participants
Part A: 1000 µg Romiplostim	Part B: Number of Participants With a Complete or Major Platelet Response	2 Participants

Secondary

Part B: Number of Participants With a Platelet Response Per IWG

Time frame: Treatment period (8 weeks) and extension period (52 weeks).

Population: Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase

Arm	Measure	Value (NUMBER)
Part A: 300 µg Romiplostim	Part B: Number of Participants With a Platelet Response Per IWG	2 Participants
Part A: 700 µg Romiplostim	Part B: Number of Participants With a Platelet Response Per IWG	4 Participants
Part A: 1000 µg Romiplostim	Part B: Number of Participants With a Platelet Response Per IWG	1 Participants

Secondary

Part B: Peak Platelet Count

Peak platelet count (10\^9/L) during the treatment period.

Time frame: Treatment Period (8 weeks)

Population: Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase.

Arm	Measure	Value (MEDIAN)
Part A: 300 µg Romiplostim	Part B: Peak Platelet Count	100.0 10^9/L
Part A: 700 µg Romiplostim	Part B: Peak Platelet Count	111.0 10^9/L
Part A: 1000 µg Romiplostim	Part B: Peak Platelet Count	83.0 10^9/L

Secondary

Part B: Time to First Platelet Response

Participants achieving first platelet response according to IWG criteria, by study week. Platelet response was defined as an absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline ≤ 20 x 10\^9/L increasing the platelet count to above 20 x 10\^9/L and by at least 100% for 8 consecutive weeks. Platelet counts obtained within 72 hours of platelet transfusion were not evaluable for platelet response.

Time frame: Treatment Period (8 weeks) and extension period (52 weeks).

Population: Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase

Arm	Measure	Group	Value (NUMBER)
Part A: 300 µg Romiplostim	Part B: Time to First Platelet Response	Week 1 Day 3	0 Participants
Part A: 300 µg Romiplostim	Part B: Time to First Platelet Response	Week 2	2 Participants
Part A: 300 µg Romiplostim	Part B: Time to First Platelet Response	Week 3	0 Participants
Part A: 300 µg Romiplostim	Part B: Time to First Platelet Response	Week 4	0 Participants
Part A: 300 µg Romiplostim	Part B: Time to First Platelet Response	Week 5 or later	0 Participants
Part A: 300 µg Romiplostim	Part B: Time to First Platelet Response	Not Observed	6 Participants
Part A: 700 µg Romiplostim	Part B: Time to First Platelet Response	Not Observed	7 Participants
Part A: 700 µg Romiplostim	Part B: Time to First Platelet Response	Week 1 Day 3	1 Participants
Part A: 700 µg Romiplostim	Part B: Time to First Platelet Response	Week 4	0 Participants
Part A: 700 µg Romiplostim	Part B: Time to First Platelet Response	Week 5 or later	1 Participants
Part A: 700 µg Romiplostim	Part B: Time to First Platelet Response	Week 2	1 Participants
Part A: 700 µg Romiplostim	Part B: Time to First Platelet Response	Week 3	1 Participants
Part A: 1000 µg Romiplostim	Part B: Time to First Platelet Response	Week 2	1 Participants
Part A: 1000 µg Romiplostim	Part B: Time to First Platelet Response	Week 3	0 Participants
Part A: 1000 µg Romiplostim	Part B: Time to First Platelet Response	Not Observed	3 Participants
Part A: 1000 µg Romiplostim	Part B: Time to First Platelet Response	Week 4	0 Participants
Part A: 1000 µg Romiplostim	Part B: Time to First Platelet Response	Week 1 Day 3	0 Participants
Part A: 1000 µg Romiplostim	Part B: Time to First Platelet Response	Week 5 or later	0 Participants

Secondary

Part B: Week 1 AUC0-4

Area under the romiplostim concentration-time curve from time zero to the last time point with quantifiable concentration (AUC0-4) during Week 1

Time frame: Week 1