Trial Outcomes & Findings for An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP (NCT NCT00508820)

NCT ID: NCT00508820

Last Updated: 2022-11-14

Results Overview

One or more occurences of one or more adverse events within the participant during the study. Participants with more than one event were only counted once

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 407 participants
• Primary outcome timeframe: Duration of Treatment plus 30 days or End of Study (whichever is later). Approximately 205 weeks.
• Results posted on: 2022-11-14

Participant Flow

First Subject Enrolled: 24Feb2005 Last Subject Enrolled: 05Jan2010

Participant milestones

Measure	Romiplostim (AMG 531) Cohort 1 Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under the original protocol or protocol amendments 1-3 where starting dose was 3mcg/kg.	Romiplostim (AMG 531) Cohort 2 Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under protocol amendments 4 where starting dose was 1mcg/kg.
Overall Study STARTED	168	239
Overall Study COMPLETED	113	175
Overall Study NOT COMPLETED	55	64

Reasons for withdrawal

Measure	Romiplostim (AMG 531) Cohort 1 Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under the original protocol or protocol amendments 1-3 where starting dose was 3mcg/kg.	Romiplostim (AMG 531) Cohort 2 Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under protocol amendments 4 where starting dose was 1mcg/kg.
Overall Study Adverse Event	6	10
Overall Study Death	6	8
Overall Study Lost to Follow-up	1	1
Overall Study Physician Decision	8	2
Overall Study Pregnancy	0	2
Overall Study Protocol Violation	2	0
Overall Study Withdrawal by Subject	10	12
Overall Study Other	11	2
Overall Study Noncompliance	1	0
Overall Study Requirement for alternative therapy	7	15
Overall Study Protocol-specified Criteria	3	12

Baseline Characteristics

An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP

Baseline characteristics by cohort

Measure	Romiplostim (AMG 531) Cohort 1 n=168 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under the original protocol or protocol amendments 1-3 where starting dose was 3mcg/kg.	Romiplostim (AMG 531) Cohort 2 n=239 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under protocol amendments 4 where starting dose was 1mcg/kg.	Total n=407 Participants Total of all reporting groups
Age, Continuous	53.6 years STANDARD_DEVIATION 17 • n=5 Participants	54.1 years STANDARD_DEVIATION 18 • n=7 Participants	53.9 years STANDARD_DEVIATION 17.6 • n=5 Participants
Sex: Female, Male Female	94 Participants n=5 Participants	150 Participants n=7 Participants	244 Participants n=5 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	89 Participants n=7 Participants	163 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	149 participants n=5 Participants	232 participants n=7 Participants	381 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	7 participants n=5 Participants	2 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Asian	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Duration of Treatment plus 30 days or End of Study (whichever is later). Approximately 205 weeks.

Population: Safety Analysis Set, comprised of all participants who received at least one dose of romiplostim

One or more occurences of one or more adverse events within the participant during the study. Participants with more than one event were only counted once

Outcome measures

Measure	Romiplostim (AMG 531) Cohort 1 n=168 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under the original protocol or protocol amendments 1-3 where starting dose was 3mcg/kg.	Romiplostim (AMG 531) Cohort 2 n=239 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under protocol amendments 4 where starting dose was 1mcg/kg.
Adverse Events	162 participants	215 participants

SECONDARY outcome

Timeframe: Duration of treatment (up to 201 weeks)

Population: Full Analysis Set, all enrolled participants

Platelet response using definition1 . (a doubling of baseline platelet count and a platelet count of >=50 x 10^9/L

Outcome measures

Measure	Romiplostim (AMG 531) Cohort 1 n=168 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under the original protocol or protocol amendments 1-3 where starting dose was 3mcg/kg.	Romiplostim (AMG 531) Cohort 2 n=239 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under protocol amendments 4 where starting dose was 1mcg/kg.
Platelet Response (Definition 1)	156 Participants	214 Participants

SECONDARY outcome

Timeframe: Duration of treatment (up to 201 weeks)

Population: Full Analysis Set, all enrolled participants

Platelet response using definition 2 (a platelet count increase of >=20 x 109/L from baseline)

Outcome measures

Measure	Romiplostim (AMG 531) Cohort 1 n=168 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under the original protocol or protocol amendments 1-3 where starting dose was 3mcg/kg.	Romiplostim (AMG 531) Cohort 2 n=239 Participants Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under protocol amendments 4 where starting dose was 1mcg/kg.
Platelet Response (Definition 2)	160 Participants	220 Participants

Adverse Events

Romiplostim Cohort 1

Serious events: 61 serious events

Other events: 155 other events

Deaths: 0 deaths

Romiplostim Cohort 2

Serious events: 61 serious events

Other events: 188 other events

Deaths: 0 deaths

Serious adverse events

Measure	Romiplostim Cohort 1 n=168 participants at risk	Romiplostim Cohort 2 n=239 participants at risk
Renal and urinary disorders Renal disorder	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Renal and urinary disorders Renal failure	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Renal and urinary disorders Renal failure acute	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Renal and urinary disorders Urogenital haemorrhage	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Menorrhagia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Vaginal haemorrhage	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.8% 3/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.0% 5/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.3% 3/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.0% 5/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory tract haemorrhage	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Pemphigus	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Petechiae	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Purpura	1.8% 3/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Skin discolouration	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Aortic stenosis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Deep vein thrombosis	1.8% 3/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Haematoma	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Haemorrhage	1.8% 3/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Hypertension	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Hypotension	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Peripheral ischaemia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Thrombophlebitis superficial	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Thrombosis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Venous thrombosis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Venous thrombosis limb	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Anaemia	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Aplasia pure red cell	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Aplastic anaemia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Bone marrow disorder	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Bone marrow reticulin fibrosis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Haemolysis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	3.0% 5/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Leukocytosis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Neutropenia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Splenomegaly	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Thrombocytopenia	6.0% 10/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 10/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Acute coronary syndrome	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Cardiac disorder	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Cardiac failure	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Coronary artery stenosis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Myocardial infarction	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Ear and labyrinth disorders Deafness	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Ear and labyrinth disorders Tinnitus	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Eye disorders Visual impairment	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Abdominal pain	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.3% 3/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Enterocolitis haemorrhagic	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Gastric perforation	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Gastritis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Gastrointestinal haemorrhage	3.0% 5/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Haemorrhoids	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Inguinal hernia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Intestinal infarction	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Mouth haemorrhage	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.3% 3/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Pancreatic pseudocyst	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Pancreatitis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Periodontitis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Peritonitis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Rectal haemorrhage	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Rectal prolapse	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Vomiting	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Chest pain	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Fatigue	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders General physical health deterioration	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Generalised oedema	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Hyperpyrexia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders No therapeutic response	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Polyp	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pyrexia	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Sudden death	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Thrombosis in device	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Hepatobiliary disorders Cholecystitis acute	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Hepatobiliary disorders Hepatic haemorrhage	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Hepatobiliary disorders Portal vein thrombosis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Acute tonsillitis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Bronchitis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Cellulitis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Cytomegalovirus infection	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Erysipelas	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Fungal sepsis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Gastroenteritis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Gastrointestinal infection	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations H1N1 influenza	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Herpes virus infection	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Infected cyst	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Infection	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Intervertebral discitis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Lower respiratory tract infection	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Osteomyelitis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pneumococcal sepsis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pneumonia	3.6% 6/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.3% 3/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pseudomonal sepsis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pyelonephritis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Respiratory syncytial virus infection	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Respiratory tract infection	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Sepsis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Septic shock	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Tuberculous pleurisy	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Upper respiratory tract infection	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Urinary tract infection	1.8% 3/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Viral infection	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Contusion	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Incision site haemorrhage	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Stab wound	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Traumatic haematoma	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Traumatic haemorrhage	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Wound	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Investigations Blood smear test abnormal	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Investigations Electrocardiogram	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Investigations Platelet count abnormal	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Investigations Platelet count decreased	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Investigations Troponin increased	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Dehydration	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hyperkalaemia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hypoglycaemia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hyponatraemia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Juvenile melanoma benign	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Amnesia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Brain oedema	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Carpal tunnel syndrome	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Cerebral haemorrhage	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Cerebrovascular accident	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Dementia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Encephalopathy	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Haemorrhage intracranial	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Headache	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Intracranial aneurysm	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Intracranial venous sinus thrombosis	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Ischaemic stroke	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Mononeuropathy multiplex	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Neuralgia	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Paraesthesia	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Subarachnoid haemorrhage	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Syncope	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Temporal lobe epilepsy	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Transient ischaemic attack	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.84% 2/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Depression	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Renal and urinary disorders Acute prerenal failure	0.00% 0/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Renal and urinary disorders Renal colic	0.60% 1/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Other adverse events

Measure	Romiplostim Cohort 1 n=168 participants at risk	Romiplostim Cohort 2 n=239 participants at risk
Blood and lymphatic system disorders Anaemia	7.7% 13/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 10/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Thrombocytopenia	8.9% 15/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.6% 11/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Abdominal pain	10.7% 18/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.6% 11/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Constipation	11.9% 20/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.0% 12/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea	19.6% 33/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.0% 24/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Dyspepsia	5.4% 9/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.1% 5/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Gingival bleeding	8.3% 14/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.1% 5/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Mouth haemorrhage	6.5% 11/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.3% 15/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	19.0% 32/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	15.9% 38/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Vomiting	7.1% 12/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.6% 11/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Asthenia	7.7% 13/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.5% 18/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Chest pain	6.0% 10/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 7/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Chills	6.5% 11/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.7% 4/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Fatigue	29.8% 50/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.5% 25/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Influenza like illness	6.5% 11/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.3% 8/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Oedema peripheral	14.3% 24/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	9.6% 23/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pain	9.5% 16/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 7/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pyrexia	11.3% 19/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.4% 13/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Influenza	5.4% 9/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.5% 25/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Nasopharyngitis	22.6% 38/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.0% 31/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Rhinitis	6.0% 10/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.7% 4/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Upper respiratory tract infection	14.3% 24/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.9% 14/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Urinary tract infection	6.5% 11/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.3% 8/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Viral infection	8.9% 15/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.42% 1/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Contusion	23.2% 39/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.8% 21/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Decreased appetite	9.5% 16/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.5% 6/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	27.4% 46/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	14.2% 34/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	16.7% 28/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.7% 16/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Bone pain	1.2% 2/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.7% 16/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Muscle spasms	8.9% 15/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.3% 8/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.7% 18/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 10/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Myalgia	12.5% 21/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.3% 15/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	16.1% 27/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.7% 28/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Dizziness	16.7% 28/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.3% 15/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Headache	33.9% 57/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	25.5% 61/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Hypoaesthesia	5.4% 9/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Paraesthesia	6.0% 10/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.7% 16/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Anxiety	6.5% 11/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.1% 5/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Depression	6.0% 10/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 7/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Insomnia	11.3% 19/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.6% 11/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	20.8% 35/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	9.2% 22/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.1% 17/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.3% 8/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.2% 34/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.0% 31/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.1% 17/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.9% 14/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Ecchymosis	5.4% 9/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.3% 3/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Petechiae	17.3% 29/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.0% 31/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Pruritus	8.3% 14/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.0% 12/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Rash	10.1% 17/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.3% 8/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Haematoma	4.8% 8/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.1% 17/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Hypertension	7.7% 13/168 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.6% 11/239 • Average duration: cohort 1 52 wks; cohort 2 42 wks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER