Trial Outcomes & Findings for ATG-GCSF in New Onset Type 1 Diabetes (NCT NCT02215200)

Last Updated: 2020-03-02

Results Overview

The C-peptide 2 hour area under the curve (AUC) mean is calculated at baseline and 12 months and measured in nmol/L. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis").

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

89 participants

Primary outcome timeframe

-10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months

Results posted on

2020-03-02

Participant Flow

Participant milestones

Participant milestones
Measure	Anti-Thymocyte Globulin (ATG) and Placebo Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose. Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF	ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg. GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)	Placebo Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF
Overall Study STARTED	29	29	31
Overall Study COMPLETED	29	28	30
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ATG-GCSF in New Onset Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anti-Thymocyte Globulin (ATG) and Placebo n=29 Participants Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose. Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF	ATG Plus Granulocyte Colony Stimulating Factor (GCSF) n=29 Participants Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg. GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)	Placebo n=31 Participants Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF	Total n=89 Participants Total of all reporting groups
Age, Continuous	17.2 Years STANDARD_DEVIATION 5 • n=5 Participants	18.1 Years STANDARD_DEVIATION 6.9 • n=7 Participants	16.9 Years STANDARD_DEVIATION 4.6 • n=5 Participants	17.4 Years STANDARD_DEVIATION 5.56 • n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	39 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	17 Participants n=7 Participants	17 Participants n=5 Participants	50 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants	27 Participants n=7 Participants	30 Participants n=5 Participants	85 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	29 Participants n=7 Participants	29 Participants n=5 Participants	86 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	29 participants n=5 Participants	29 participants n=7 Participants	31 participants n=5 Participants	89 participants n=4 Participants

PRIMARY outcome

Timeframe: -10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months

Outcome measures

Outcome measures
Measure	Anti-Thymocyte Globulin (ATG) and Placebo n=29 Participants Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose. Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF	ATG Plus Granulocyte Colony Stimulating Factor (GCSF) n=28 Participants Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg. GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)	Placebo n=30 Participants Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF
Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months.	0.528 nmol/L Interval 0.435 to 0.627	0.646 nmol/L Interval 0.547 to 0.75	0.406 nmol/L Interval 0.324 to 0.494

Adverse Events

Anti-Thymocyte Globulin (ATG) and Placebo

Serious events: 28 serious events

Other events: 28 other events

Deaths: 0 deaths

ATG Plus Granulocyte Colony Stimulating Factor (GCSF)

Serious events: 29 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Anti-Thymocyte Globulin (ATG) and Placebo n=29 participants at risk Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose. Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF	ATG Plus Granulocyte Colony Stimulating Factor (GCSF) n=29 participants at risk Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg. GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)	Placebo n=31 participants at risk Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF
Immune system disorders All immune system disorders	41.4% 12/29 • Number of events 14 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	51.7% 15/29 • Number of events 15 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Blood and lymphatic system disorders CD4 lymphocyte decrease or other	62.1% 18/29 • Number of events 24 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	58.6% 17/29 • Number of events 23 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders General Disorders and administration	6.9% 2/29 • Number of events 4 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Endocrine disorders Endocrine Disorders	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 5 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Infections and infestations	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Gastrointestinal Disorders	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Surgical and medical procedures Surgical and medical procedures	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Psychiatric disorders Psychiatric Disorders	3.4% 1/29 • Number of events 3 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Injury, poisoning and procedural complications Injury, poisoning, and procedural complications	3.4% 1/29 • Number of events 2 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Nervous system disorders	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Metabolism and nutrition disorders	6.9% 2/29 • Number of events 3 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	6.5% 2/31 • Number of events 2 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms: benign, malignant, and unspecified	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Blood and lymphatic system disorders Blood and lymphatic system disorder	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Other adverse events

Additional Information

Carla Greenbaum, MD

Benaroya Research Institute

Phone: 1-800-425-8361

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Anti-Thymocyte Globulin (ATG) and Placebo n=29 participants at risk Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose. Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF	ATG Plus Granulocyte Colony Stimulating Factor (GCSF) n=29 participants at risk Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg. GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses Anti-Thymocyte Globulin (ATG): Thymoglobulin Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)	Placebo n=31 participants at risk Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorder	17.2% 5/29 • Number of events 6 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	24.1% 7/29 • Number of events 10 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	12.9% 4/31 • Number of events 7 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Immune system disorders All Immune system disorders	72.4% 21/29 • Number of events 33 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	79.3% 23/29 • Number of events 38 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue	34.5% 10/29 • Number of events 14 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	10.3% 3/29 • Number of events 3 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	16.1% 5/31 • Number of events 6 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Blood and lymphatic system disorders CD4 lymphocyte decrease or other	72.4% 21/29 • Number of events 42 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	75.9% 22/29 • Number of events 43 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	9.7% 3/31 • Number of events 4 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders General Disorders and administration	24.1% 7/29 • Number of events 16 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	27.6% 8/29 • Number of events 18 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Endocrine disorders Endocrine Disorders	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	9.7% 3/31 • Number of events 7 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Infections and infestations	31.0% 9/29 • Number of events 14 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	24.1% 7/29 • Number of events 9 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	29.0% 9/31 • Number of events 16 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Gastrointestinal Disorders	17.2% 5/29 • Number of events 7 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	10.3% 3/29 • Number of events 5 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	19.4% 6/31 • Number of events 6 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Surgical and medical procedures Surgical and medical procedures	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Psychiatric disorders Psychiatric Disorders	6.9% 2/29 • Number of events 7 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Injury, poisoning and procedural complications Injury, poisoning, and procedural complications	3.4% 1/29 • Number of events 4 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	6.9% 2/29 • Number of events 2 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	16.1% 5/31 • Number of events 5 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Nervous system disorders	13.8% 4/29 • Number of events 4 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	13.8% 4/29 • Number of events 11 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	6.5% 2/31 • Number of events 5 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Metabolism and nutrition disorders	13.8% 4/29 • Number of events 7 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	6.9% 2/29 • Number of events 4 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	12.9% 4/31 • Number of events 4 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Vascular disorders Vascular Disorders	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	6.9% 2/29 • Number of events 2 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms: benign, malignant, and unspecified	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic, and mediastinal	6.9% 2/29 • Number of events 2 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	6.9% 2/29 • Number of events 3 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.2% 1/31 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Blood and lymphatic system disorders Blood and lymphatic system disorder	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	6.5% 2/31 • Number of events 2 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Cardiac Disorders	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Ear and labyrinth disorders Ear and labyrinth disorders	3.4% 1/29 • Number of events 1 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/29 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	0.00% 0/31 • Adverse events were collected over 1 year. Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.