Trial Outcomes & Findings for Study of Antithymocyte Globulin for Treatment of New-onset T1DM (NCT NCT00515099)

Last Updated: 2017-05-11

Results Overview

C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Baseline (Pre-treatment initiation), Month 12

Results posted on

2017-05-11

Participant Flow

Subjects were recruited during an approximate 40-month accrual period. Initially 66 subjects were planned, however enrollment closed early at 58 subjects on June 30, 2011 secondary to slow accrual (planned 30-month accrual period).

Subjects ages 12 to 35 years who were first diagnosed with type 1 diabetes mellitus (T1DM) within 100 days of enrollment.

Participant milestones

Participant milestones
Measure	Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Overall Study STARTED	20	38
Overall Study COMPLETED	16	35
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Overall Study Lost to Follow-up	4	0
Overall Study Withdrawal by Subject	0	2
Overall Study IRB Recommendation	0	1

Baseline Characteristics

Study of Antithymocyte Globulin for Treatment of New-onset T1DM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Total n=58 Participants Total of all reporting groups
Age, Categorical <=18 years	19 Participants n=5 Participants	10 Participants n=7 Participants	29 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	10 Participants n=7 Participants	29 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	19.4 years STANDARD_DEVIATION 6.6 • n=5 Participants	20.5 years STANDARD_DEVIATION 7.1 • n=7 Participants	19.8 years STANDARD_DEVIATION 6.7 • n=5 Participants
Age, Customized 12 -15 Years	13 participants n=5 Participants	6 participants n=7 Participants	19 participants n=5 Participants
Age, Customized 16 - 21 Years	13 participants n=5 Participants	6 participants n=7 Participants	19 participants n=5 Participants
Age, Customized 22 - 35 Years	12 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	11 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment United States	38 participants n=5 Participants	20 participants n=7 Participants	58 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Pre-treatment initiation), Month 12

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) Change from Baseline (Pre-treatment initiation)	-0.20 pmol/mL Standard Deviation 0.29	-0.24 pmol/mL Standard Deviation 0.26
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) Baseline (Pre-treatment initiation)	0.86 pmol/mL Standard Deviation 0.37	0.93 pmol/mL Standard Deviation 0.50
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) Month 12	0.66 pmol/mL Standard Deviation 0.37	0.69 pmol/mL Standard Deviation 0.52

SECONDARY outcome

Timeframe: Baseline (Pre-treatment initiation), Month 12

Population: Intent-to-treat

C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 4-hour (e.g., 240 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.

Outcome measures

Outcome measures
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) Baseline (Pre-treatment initiation)	0.86 pmol/mL Standard Deviation 0.30	0.90 pmol/mL Standard Deviation 0.37
4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) Month 12	0.67 pmol/mL Standard Deviation 0.38	0.63 pmol/mL Standard Deviation 0.39
4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) Change from Baseline (Pre-treatment initiation)	-0.19 pmol/mL Standard Deviation 0.30	-0.27 pmol/mL Standard Deviation 0.25

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Months 12 and 24

Population: Intent-to-treat

The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.

Outcome measures

Outcome measures
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Insulin Use in Units Per Kilogram Body Weight Per Day Baseline (Pre-treatment initiation)	0.34 units/day/kg Standard Deviation 0.22	0.42 units/day/kg Standard Deviation 0.24
Insulin Use in Units Per Kilogram Body Weight Per Day Change from Baseline to Month 12	0.07 units/day/kg Standard Deviation 0.20	0.08 units/day/kg Standard Deviation 0.20
Insulin Use in Units Per Kilogram Body Weight Per Day Month 24	0.54 units/day/kg Standard Deviation 0.31	0.47 units/day/kg Standard Deviation 0.21
Insulin Use in Units Per Kilogram Body Weight Per Day Month 12	0.40 units/day/kg Standard Deviation 0.24	0.49 units/day/kg Standard Deviation 0.26
Insulin Use in Units Per Kilogram Body Weight Per Day Change from Baseline to Month 24	0.19 units/day/kg Standard Deviation 0.23	0.06 units/day/kg Standard Deviation 0.25

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Months 12 , 18, and 24

Population: Intent-to-treat

The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.

Outcome measures

Outcome measures
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Number of Participants Who Are Exogenous-Insulin-Free Month 24	1 participants	0 participants
Number of Participants Who Are Exogenous-Insulin-Free Baseline (Pre-treatment initiation)	1 participants	0 participants
Number of Participants Who Are Exogenous-Insulin-Free Month 12	1 participants	0 participants
Number of Participants Who Are Exogenous-Insulin-Free Month 18	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Months 12 , and 24

Population: Intent-to-treat

Major hypoglycemic events are defined as a glucose concentration \<55 mg/dL (grades 2-5, NCI-CTCAE version 3.0), or clinically: involving seizure(s) or involving loss of consciousness (coma), or requiring assistance from another individual in order to recover.

Outcome measures

Outcome measures
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation Participants with Hypoglycemic Events Up to Mo. 12	23 participants	12 participants
Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation Participants with Hypoglycemic Events Up to Mo. 24	30 participants	15 participants

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Month 24

Population: Intent-to-treat

C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) and 4-hour (e.g., 240 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the CDER at the FDA as a valid efficacy endpoint.

Outcome measures

Outcome measures
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) Baseline (Pre-treatment initiation)	0.86 pmol/mL Standard Deviation 0.37	0.93 pmol/mL Standard Deviation 0.50
2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) 2-hour AUC Month 24	0.58 pmol/mL Standard Deviation 0.43	0.61 pmol/mL Standard Deviation 0.67
2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) Change from 2-hr MMTT Baseline	-0.27 pmol/mL Standard Deviation 0.31	-0.32 pmol/mL Standard Deviation 0.32
2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) 4-hour AUC Month 24	0.56 pmol/mL Standard Deviation 0.36	0.59 pmol/mL Standard Deviation 0.63
2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) Change from 4-hr MMTT Baseline	-0.26 pmol/mL Standard Deviation 0.28	-0.31 pmol/mL Standard Deviation 0.38

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Months 12 and 24

Population: Intent-to-treat

Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of \<\\=5.6% is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM).

Outcome measures

Outcome measures
Measure	Antithymocyte Globulin n=38 Participants This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.	Placebo n=20 Participants This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Hemoglobin A1c Baseline (Pre-treatment initiation)	6.7 Percentage (%) Standard Deviation 1.3	6.8 Percentage (%) Standard Deviation 1.2
Hemoglobin A1c Change from Baseline to Month 24	0.6 Percentage (%) Standard Deviation 1.8	1.4 Percentage (%) Standard Deviation 1.9
Hemoglobin A1c Month 12	6.9 Percentage (%) Standard Deviation 1.6	7.7 Percentage (%) Standard Deviation 1.8
Hemoglobin A1c Change from Baseline to Month 12	0.1 Percentage (%) Standard Deviation 1.8	1.0 Percentage (%) Standard Deviation 1.5
Hemoglobin A1c Month 24	7.5 Percentage (%) Standard Deviation 1.5	8.2 Percentage (%) Standard Deviation 2.4

Adverse Events

Antithymocyte Globulin

Serious events: 9 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Antithymocyte Globulin n=38 participants at risk This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4 2 mg/kg.	Placebo n=20 participants at risk This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4 2 mg/kg.
Immune system disorders Cytokine release syndrome	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Immune system disorders Serum sickness	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Infections and infestations Appendicitis	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Infections and infestations Gastroenteritis viral	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Infections and infestations Salmonellosis	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Infections and infestations Viral infection	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Injury, poisoning and procedural complications Comminuted fracture	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Investigations CD4 lymphocytes decreased	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Metabolism and nutrition disorders Hyperglycaemia	5.3% 2/38 • Number of events 4 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Metabolism and nutrition disorders Hypoglycaemia	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Metabolism and nutrition disorders Ketosis	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Nervous system disorders Syncope	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Psychiatric disorders Affective disorder	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Psychiatric disorders Bipolar disorder	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Psychiatric disorders Depression	2.6% 1/38 • Number of events 4 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Psychiatric disorders Major depression	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Psychiatric disorders Mood altered	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Psychiatric disorders Substance abuse	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Psychiatric disorders Suicidal ideation	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Skin and subcutaneous tissue disorders Exfoliative rash	2.6% 1/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Vascular disorders Axillary vein thrombosis	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.

Other adverse events
Measure	Antithymocyte Globulin n=38 participants at risk This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4 2 mg/kg.	Placebo n=20 participants at risk This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4 2 mg/kg.
Gastrointestinal disorders Nausea	18.4% 7/38 • Number of events 8 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	25.0% 5/20 • Number of events 7 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Oral disorder	5.3% 2/38 • Number of events 4 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Blood and lymphatic system disorders Leukopenia	36.8% 14/38 • Number of events 20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Blood and lymphatic system disorders Lymphadenopathy	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	10.0% 2/20 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Blood and lymphatic system disorders Lymphopenia	100.0% 38/38 • Number of events 48 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Blood and lymphatic system disorders Neutropenia	23.7% 9/38 • Number of events 10 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	10.0% 2/20 • Number of events 4 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Blood and lymphatic system disorders Thrombocytopenia	13.2% 5/38 • Number of events 5 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Cardiac disorders Bradycardia	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Ear and labyrinth disorders Ear pain	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Ear and labyrinth disorders Middle ear effusion	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Eye disorders Eye irritation	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Eye disorders Ocular hyperaemia	7.9% 3/38 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Eye disorders Visual impairment	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Abdominal pain	7.9% 3/38 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Abdominal pain lower	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Abdominal pain upper	7.9% 3/38 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Constipation	13.2% 5/38 • Number of events 6 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Diarrhoea	13.2% 5/38 • Number of events 5 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	15.0% 3/20 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Dyspepsia	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	15.0% 3/20 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Gastritis	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Toothache	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Gastrointestinal disorders Vomiting	7.9% 3/38 • Number of events 4 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	15.0% 3/20 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Catheter site pain	13.2% 5/38 • Number of events 5 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Chest discomfort	7.9% 3/38 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Chest pain	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Face oedema	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Fatigue	7.9% 3/38 • Number of events 4 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	20.0% 4/20 • Number of events 5 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Influenza like illness	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	15.0% 3/20 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Infusion site pain	2.6% 1/38 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Infusion site swelling	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Injection site discolouration	0.00% 0/38 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Injection site hypertrophy	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Malaise	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Pain	5.3% 2/38 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
General disorders Pyrexia	15.8% 6/38 • Number of events 6 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Hepatobiliary disorders Hyperbilirubinaemia	7.9% 3/38 • Number of events 3 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Immune system disorders Cytokine release syndrome	94.7% 36/38 • Number of events 36 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	5.0% 1/20 • Number of events 1 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Immune system disorders Seasonal allergy	18.4% 7/38 • Number of events 8 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	10.0% 2/20 • Number of events 2 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.
Immune system disorders Serum sickness	94.7% 36/38 • Number of events 37 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.	0.00% 0/20 • From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013. Adverse Events (AEs) could be discovered through any of these methods: * Observing the participant. * Questioning the participant in an objective manner. * Receiving an unsolicited complaint from the participant.