Trial Outcomes & Findings for Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD) (NCT NCT02592798)

NCT ID: NCT02592798

Last Updated: 2021-03-05

Results Overview

Renal Response is defined as the presence of all the following criteria: PROTEINURIA: Reduction of baseline urine protein/creatinine ratio (UPCR) of \>= 50% and to less than 3. RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 36 participants
• Primary outcome timeframe: From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period)
• Results posted on: 2021-03-05

Participant Flow

36 participants were randomized and treated.

Participant milestones

Measure	Abatacept * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administer on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days
Double-Blind Period 1 (DB1) STARTED	17	19
Double-Blind Period 1 (DB1) COMPLETED	14	13
Double-Blind Period 1 (DB1) NOT COMPLETED	3	6
Transition From DB1 to DB2 STARTED	14	13
Transition From DB1 to DB2 COMPLETED	11	11
Transition From DB1 to DB2 NOT COMPLETED	3	2
Double-Blind Period 2 (DB2) STARTED	11	11
Double-Blind Period 2 (DB2) COMPLETED	6	9
Double-Blind Period 2 (DB2) NOT COMPLETED	5	2
Transition From DB2 to OLE STARTED	6	9
Transition From DB2 to OLE COMPLETED	5	9
Transition From DB2 to OLE NOT COMPLETED	1	0
Open Label Period (OLE) STARTED	10	13
Open Label Period (OLE) COMPLETED	6	4
Open Label Period (OLE) NOT COMPLETED	4	9

Reasons for withdrawal

Measure	Abatacept * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administer on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days
Double-Blind Period 1 (DB1) Pregnancy	1	0
Double-Blind Period 1 (DB1) No longer meeting study criteria	0	1
Double-Blind Period 1 (DB1) Lack of Efficacy	1	3
Double-Blind Period 1 (DB1) Adverse Event	1	2
Transition From DB1 to DB2 Skipped DB2 and moved into subsequent OLE	3	2
Double-Blind Period 2 (DB2) Other reasons	1	0
Double-Blind Period 2 (DB2) Participant request to discontinue	1	0
Double-Blind Period 2 (DB2) No longer meeting study criteria	1	0
Double-Blind Period 2 (DB2) Lack of Efficacy	1	2
Double-Blind Period 2 (DB2) Adverse Event	1	0
Transition From DB2 to OLE Other reasons	1	0
Open Label Period (OLE) Other reasons	0	2
Open Label Period (OLE) Participant request to discontinue	1	0
Open Label Period (OLE) Lost to Follow-up	0	1
Open Label Period (OLE) Lack of Efficacy	3	5
Open Label Period (OLE) Adverse Event	0	1

Baseline Characteristics

Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)

Baseline characteristics by cohort

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Total n=36 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Age, Continuous	22.5 Years STANDARD_DEVIATION 13.21 • n=5 Participants	28.7 Years STANDARD_DEVIATION 19.35 • n=7 Participants	25.8 Years STANDARD_DEVIATION 16.80 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period)

Population: All treated participants with available measurements

Renal Response is defined as the presence of all the following criteria:

PROTEINURIA: Reduction of baseline urine protein/creatinine ratio (UPCR) of >= 50% and to less than 3.

RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline.

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Percentage of Participants in Renal Response at Day 113 Double-Blind Period Day 113	0.0 Percent of Participants Interval 0.0 to 24.7	7.7 Percent of Participants Interval 0.2 to 36.0	—
Percentage of Participants in Renal Response at Day 113 Open Label Period Day 113	12.5 Percent of Participants Interval 0.3 to 52.7	33.3 Percent of Participants Interval 7.5 to 70.1	—

SECONDARY outcome

Timeframe: From baseline (measured at day 1 of study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period)

Population: All treated participants with available measurements

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 Double-Blind Period Day 113	0.12 mg/mg Standard Error 0.5738	-0.25 mg/mg Standard Error 0.7914	—
Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 Open Label Period Day 113	1.98 mg/mg Standard Error 1.1598	0.02 mg/mg Standard Error 1.3049	—

SECONDARY outcome

Timeframe: From baseline (measured at day 1 of the study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period)

Population: All treated participants with available measurements

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Mean Change From Baseline in Serum Albumine at Day 113 Double-Blind Period Day 113	0.08 g/dL Standard Error 0.1016	-0.05 g/dL Standard Error 0.0892	—
Mean Change From Baseline in Serum Albumine at Day 113 Open Label Period Day 113	0.21 g/dL Standard Error 0.1829	0.09 g/dL Standard Error 0.2360	—

SECONDARY outcome

Timeframe: From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period)

Population: All treated participants with available measurements

Complete Remission is defined as the presence of all the following criteria:

PROTEINURIA: Urine protein/creatinine ratio (UPCR) ≤ 0.3. RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline.

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Percentage of Participants Achieving Complete Remission at Day 113 Double-Blind Period Day 113	0.0 Percent of Participants Interval 0.0 to 24.7	0.0 Percent of Participants Interval 0.0 to 24.7	—
Percentage of Participants Achieving Complete Remission at Day 113 Open Label Period Day 113	12.5 Percent of Participants Interval 0.3 to 52.7	11.1 Percent of Participants Interval 0.3 to 48.2	—

SECONDARY outcome

Timeframe: From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period

Population: All treated participants with available measurements

PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements:

Fatigue: Short From (SF) Fatigue v1.0 Adult 8a, composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome).

Pain Interference: SF Pain Interference v1.0 Adult 8a, (measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome).

Physical Function: SF Physical Function v1.2 Adult 8b, composed of 8 questions, each one scored from 1 (Without any difficulty) to 5 (Unable to do). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome).

Outcome measures

Measure	Abatacept n=9 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=11 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants Fatigue	-5.56 Score on a scale Standard Error 2.2907	-4.87 Score on a scale Standard Error 2.6125	—
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants Pain Interference	-4.88 Score on a scale Standard Error 2.6395	-1.18 Score on a scale Standard Error 3.9785	—
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants Physical Function	0.78 Score on a scale Standard Error 1.7350	1.77 Score on a scale Standard Error 1.9346	—

SECONDARY outcome

Timeframe: From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period

Population: All treated participants with available measurements

PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements:

Fatigue: Short From (SF) Fatigue v1.0 Peds 10a, composed of 10 questions, each one scored from 0 (Never) to 4 (Almost Always). Output presented as Total score, ranging from 0 (most desirable outcome) to 40 (least desirable outcome).

Pain Interference: SF Pain Interference v1.0 Peds 8a, ( measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 0 (Never) to 4 (Almost always). Output presented as Total score, ranging from 0 (most desirable outcome) to 32 (least desirable outcome).

Mobility: SF Physical Function-Mobility v1.0 Peds 8a, composed of 8 questions, each one scored from 0 (Not able to do) to 4 (With no trouble). Output presented as Total score, ranging from 0 (least desirable outcome) to 32 (most desirable outcome).

Outcome measures

Measure	Abatacept n=8 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=8 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants Fatigue	6.43 Score on a scale Standard Error 6.7142	-6.02 Score on a scale Standard Error 3.6526	—
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants Pain Interference	5.70 Score on a scale Standard Error 3.9781	-1.44 Score on a scale Standard Error 1.9180	—
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants Mobility	0.80 Score on a scale Standard Error 3.5007	1.68 Score on a scale Standard Error 3.1905	—

SECONDARY outcome

Timeframe: From first dose in the indicated period to 56 days following last dose in the indicated period (169 days for the Double-Blind Period, up to 337 days for the Cumulative Abatacept Safety Period)

Population: All treated participants

This outcome describes the number of participants experiencing various types of any grade Adverse Events (AEs).

The Cumulative Abatacept Safety Period starts at the time of the first dose of Abatacept (either in the Double-Blind Period or in the Open Label Period) and lasts 56 days after the last dose of Abatacept

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period n=32 Participants Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Number of Participants Experiencing Adverse Events AEs leading to discontinuation	1 Participants	2 Participants	2 Participants
Number of Participants Experiencing Adverse Events Adverse Events (AEs)	13 Participants	15 Participants	26 Participants
Number of Participants Experiencing Adverse Events Serious Adverse Events (SAEs)	5 Participants	4 Participants	10 Participants
Number of Participants Experiencing Adverse Events Deaths	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose on day 1 to 56 days following last dose (approximately 330 days)

Population: All treated participants

Number of participants experiencing various types of Adverse Events of interest, including infections, malignancies, autoimmune disorders, and infusional related reactions.

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Number of Participants Experiencing Adverse Events of Special Interest Peri-infusional Adverse Event (AE)	6 Participants	3 Participants	—
Number of Participants Experiencing Adverse Events of Special Interest AE within 24 hours of Infusion	8 Participants	9 Participants	—
Number of Participants Experiencing Adverse Events of Special Interest Malignancies	0 Participants	0 Participants	—
Number of Participants Experiencing Adverse Events of Special Interest Infections/Infestations	12 Participants	10 Participants	—
Number of Participants Experiencing Adverse Events of Special Interest Autoimmune disorders	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: From baseline (day 1) to 168 days following last dose (up to 15 months). Results at day 113 from first dose, day 56, day 84 and day 168 after last dose are presented

Population: All treated participants with available measurements

A positive response relative to baseline is defined as a positive response at a post-baseline visit that has a titer value greater than the positive baseline titer value. If the baseline titer is missing or negative, any post-baseline positive titer value is considered a positive response relative to baseline.

Immunogenicity response is presented as the total of immunogenicity response for "CTLA4 and possibly Ig" and "Ig and/or Junction Region".

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Percentage of Participants With Positive Antibody Response Relative to Baseline Day 113 from first dose	7.1 Percent of Participants	0.0 Percent of Participants	—
Percentage of Participants With Positive Antibody Response Relative to Baseline Day 56 from last dose	40.0 Percent of Participants	66.7 Percent of Participants	—
Percentage of Participants With Positive Antibody Response Relative to Baseline Day 84 from last dose	28.6 Percent of Participants	66.7 Percent of Participants	—
Percentage of Participants With Positive Antibody Response Relative to Baseline Day 168 from last dose	16.7 Percent of Participants	25.0 Percent of Participants	—

SECONDARY outcome

Timeframe: From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113

Population: All adult participants receiving Abatacept during the Double Blind Period with available measurements

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants Day 15	7.613 ug/mL Geometric Coefficient of Variation 63.7	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants Day 29	12.274 ug/mL Geometric Coefficient of Variation 86.7	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants Day 57	3.641 ug/mL Geometric Coefficient of Variation 66.5	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants Day 85	4.101 ug/mL Geometric Coefficient of Variation 52.7	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants Day 113	2.786 ug/mL Geometric Coefficient of Variation 68.2	—	—

SECONDARY outcome

Timeframe: From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113

Population: All pediatric participants receiving Abatacept during the Double Blind Period with available measurements

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants Day 15	2.829 ug/mL Geometric Coefficient of Variation 116.4	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants Day 29	2.588 ug/mL Geometric Coefficient of Variation 138.7	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants Day 57	0.504 ug/mL Geometric Coefficient of Variation 143.2	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants Day 85	1.617 ug/mL Geometric Coefficient of Variation 123.5	—	—
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants Day 113	0.990 ug/mL Geometric Coefficient of Variation 163.1	—	—

SECONDARY outcome

Timeframe: Day 85 after first dose in the Double Blind Period

Population: All participants receiving Abatacept during the Double Blind Period with available measurements

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Maximum Observed Serum Concentration (Cmax) of Abatacept Adult participants	200.46 ug/mL Geometric Coefficient of Variation 43.9	—	—
Maximum Observed Serum Concentration (Cmax) of Abatacept Pediatric participants	174.65 ug/mL Geometric Coefficient of Variation 30.0	—	—

SECONDARY outcome

Timeframe: From Day 85 to Day 113 in the Double Blind Period

Population: All participants receiving Abatacept during the Double Blind Period with available measurements

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept Adult participants	20394.83 ug*h/mL Geometric Coefficient of Variation 44.3	—	—
Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept Pediatric participants	18282.50 ug*h/mL Geometric Coefficient of Variation 41.9	—	—

SECONDARY outcome

Timeframe: Day 85 after first dose in the Double Blind Period

Population: All participants receiving Abatacept during the Double Blind Period with available measurements

Outcome measures

Measure	Abatacept n=17 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Placebo n=19 Participants * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days	Abatacept During Cumulative Abatacept Safety Period Any participants receiving at least 1 dose of Abatacept, starting either in the Double-Blind Period or in the Open Label Period
Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept Adult participants	0.883 Hours Standard Deviation 0.242	—	—
Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept Pediatric participants	0.589 Hours Standard Deviation 0.285	—	—

Adverse Events

Abatacept During Double-Blind Period 1 (DB1)

Serious events: 5 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo During Double-Blind Period 1 (DB1)

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Abatacept During Double-Blind Period 2 (DB2)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo During Double-Blind Period 2 (DB2)

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Abatacept During Open Label Period (OLE)

Serious events: 6 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Abatacept During Double-Blind Period 1 (DB1) n=17 participants at risk Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Placebo During Double-Blind Period 1 (DB1) n=19 participants at risk Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Abatacept During Double-Blind Period 2 (DB2) n=11 participants at risk Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Placebo During Double-Blind Period 2 (DB2) n=11 participants at risk Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Abatacept During Open Label Period (OLE) n=23 participants at risk Abatacept IV administered every 28 days
Blood and lymphatic system disorders Anaemia	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Blood and lymphatic system disorders Thrombotic microangiopathy	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Cardiac disorders Palpitations	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Eye disorders Periorbital swelling	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Diarrhoea	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Lip swelling	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Chest pain	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Generalised oedema	11.8% 2/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Oedema	11.8% 2/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Oedema peripheral	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Parainfluenzae virus infection	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Pneumonia	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Blood creatinine increased	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	8.7% 2/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Metabolism and nutrition disorders Fluid overload	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Metabolism and nutrition disorders Metabolic acidosis	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Nervous system disorders Seizure	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Renal and urinary disorders Acute kidney injury	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Renal and urinary disorders Nephrotic syndrome	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Renal and urinary disorders Renal disorder	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Renal and urinary disorders Renal failure	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Renal and urinary disorders Renal impairment	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Renal and urinary disorders Renal tubular necrosis	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)

Other adverse events

Measure	Abatacept During Double-Blind Period 1 (DB1) n=17 participants at risk Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Placebo During Double-Blind Period 1 (DB1) n=19 participants at risk Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Abatacept During Double-Blind Period 2 (DB2) n=11 participants at risk Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Placebo During Double-Blind Period 2 (DB2) n=11 participants at risk Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.	Abatacept During Open Label Period (OLE) n=23 participants at risk Abatacept IV administered every 28 days
Infections and infestations Pulpitis dental	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Sinusitis	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Upper respiratory tract infection	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	17.4% 4/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Viral pharyngitis	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Injury, poisoning and procedural complications Contusion	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Injury, poisoning and procedural complications Fall	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Injury, poisoning and procedural complications Heat cramps	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Injury, poisoning and procedural complications Infusion related reaction	11.8% 2/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Injury, poisoning and procedural complications Patella fracture	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Blood and lymphatic system disorders Anaemia	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Blood and lymphatic system disorders Leukopenia	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Blood and lymphatic system disorders Nephrogenic anaemia	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Blood and lymphatic system disorders Splenomegaly	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Cardiac disorders Tachycardia	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Ear and labyrinth disorders Middle ear effusion	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Endocrine disorders Hypothyroidism	11.8% 2/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Eye disorders Eye inflammation	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Abdominal pain	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Abdominal pain upper	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	8.7% 2/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Diarrhoea	23.5% 4/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	15.8% 3/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	13.0% 3/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Dyspepsia	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	8.7% 2/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Gastrooesophageal reflux disease	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Mouth ulceration	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Nausea	11.8% 2/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	17.4% 4/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Gastrointestinal disorders Vomiting	29.4% 5/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	13.0% 3/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Chest pain	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Complication associated with device	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Energy increased	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Face oedema	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	8.7% 2/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Fatigue	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Feeling cold	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Malaise	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Nodule	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Non-cardiac chest pain	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Oedema	23.5% 4/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Oedema peripheral	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	15.8% 3/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Pain	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Pyrexia	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	17.4% 4/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
General disorders Swelling	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Immune system disorders Hypersensitivity	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Immune system disorders Seasonal allergy	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Bronchitis	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Ear infection	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Furuncle	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Gastroenteritis viral	11.8% 2/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Gastrointestinal infection	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Gastrointestinal viral infection	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Influenza	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Infections and infestations Nasopharyngitis	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Injury, poisoning and procedural complications Post-traumatic pain	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Injury, poisoning and procedural complications Tendon rupture	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Blood albumin decreased	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Blood creatinine increased	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Blood pressure increased	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Blood triglycerides increased	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Influenza A virus test positive	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Respiratory syncytial virus test positive	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Investigations Weight increased	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Metabolism and nutrition disorders Decreased appetite	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Metabolism and nutrition disorders Dehydration	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Metabolism and nutrition disorders Gout	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Metabolism and nutrition disorders Hypoalbuminaemia	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Musculoskeletal and connective tissue disorders Muscle spasms	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Musculoskeletal and connective tissue disorders Myalgia	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	18.2% 2/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Nervous system disorders Dizziness	17.6% 3/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Nervous system disorders Headache	11.8% 2/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	26.3% 5/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	18.2% 2/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	8.7% 2/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Nervous system disorders Visual field defect	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Psychiatric disorders Depression	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	13.0% 3/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Psychiatric disorders Insomnia	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Psychiatric disorders Panic attack	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Renal and urinary disorders Nephrotic syndrome	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Reproductive system and breast disorders Amenorrhoea	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Reproductive system and breast disorders Menorrhagia	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Reproductive system and breast disorders Polymenorrhoea	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Asthma	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Cough	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	8.7% 2/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Hyperventilation	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	17.4% 4/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	8.7% 2/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Acne	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Alopecia areata	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Eczema	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Hyperhidrosis	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Rash	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	5.3% 1/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	9.1% 1/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Skin and subcutaneous tissue disorders Skin lesion inflammation	5.9% 1/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/23 • From first dose to 100 days following administration of last dose (approximately 1 year)
Vascular disorders Hypertension	0.00% 0/17 • From first dose to 100 days following administration of last dose (approximately 1 year)	10.5% 2/19 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	0.00% 0/11 • From first dose to 100 days following administration of last dose (approximately 1 year)	4.3% 1/23 • From first dose to 100 days following administration of last dose (approximately 1 year)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER