Trial Outcomes & Findings for GAUSS: A Study of Obinutuzumab (RO5072759) in Patients With Indolent Non-Hodgkin's Lymphoma (NCT NCT00576758)

Results Overview

Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigator at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

175 participants

Primary outcome timeframe

Randomization to clinical cutoff: 01 September 2011 (Up to 70 days)

Results posted on

2014-08-19

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Induction Treatment Period STARTED	87	88
Induction Treatment Period Received Treatment	86	87
Induction Treatment Period COMPLETED	79	83
Induction Treatment Period NOT COMPLETED	8	5
Extension Treatment Period STARTED	72	73
Extension Treatment Period COMPLETED	30	30
Extension Treatment Period NOT COMPLETED	42	43
Follow-up Period STARTED	55	51
Follow-up Period COMPLETED	28	34
Follow-up Period NOT COMPLETED	27	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Induction Treatment Period Adverse event or Intercurrent illness	3	3
Induction Treatment Period Insufficient therapeutic response	2	0
Induction Treatment Period Violation of selection criteria at entry	1	1
Induction Treatment Period Death	1	0
Induction Treatment Period Refused treatment/ Did not Cooperate	0	1
Induction Treatment Period Withdrew consent	1	0
Extension Treatment Period Adverse event or Intercurrent illness	6	7
Extension Treatment Period Death	1	1
Extension Treatment Period Refused treatment/did not cooperate	2	1
Extension Treatment Period Insufficient therapeutic response	30	33
Extension Treatment Period Administrative/Other	3	1
Follow-up Period Administrative/Other	6	8
Follow-up Period Death	3	3
Follow-up Period Insufficient therapeutic response	16	5
Follow-up Period Withdrew consent	2	1

Baseline Characteristics

GAUSS: A Study of Obinutuzumab (RO5072759) in Patients With Indolent Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab n=87 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=88 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Total n=175 Participants Total of all reporting groups
Age, Customized <65 years	49 participants n=5 Participants	47 participants n=7 Participants	96 participants n=5 Participants
Age, Customized 65-70 years	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Age, Customized >70 years	16 participants n=5 Participants	19 participants n=7 Participants	35 participants n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	42 Participants n=7 Participants	85 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	46 Participants n=7 Participants	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to clinical cutoff: 01 September 2011 (Up to 70 days)

Population: Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigator at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Percentage of Participants With Overall Response At the End of Induction Period	33.3 Percentage of participants	44.6 Percentage of participants

SECONDARY outcome

Timeframe: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)

Population: Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR is defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. All lymph nodes and nodal masses must have regressed to normal size. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. Any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Other organs considered to be enlarged before therapy due to involvement by lymphoma, such as liver and kidneys, must have decreased in size. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Percentage of Participants With Complete Response at the End of the Induction Period	5.3 Percentage of participants Interval 1.5 to 13.1	12.2 Percentage of participants Interval 5.7 to 21.8

SECONDARY outcome

Timeframe: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)

Population: Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Percentage of Participants With Partial Response (PR) at the End of the Induction Period	28.0 Percentage of participants Interval 18.2 to 39.6	32.4 Percentage of participants Interval 22.0 to 44.3

SECONDARY outcome

Timeframe: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)

Population: Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Complete Response	18.7 Percentage of participants Interval 10.6 to 29.3	35.1 Percentage of participants Interval 24.4 to 47.1
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Partial Response	45.3 Percentage of participants Interval 33.8 to 57.3	31.1 Percentage of participants Interval 20.8 to 42.9
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Stable Disease	26.7 Percentage of participants Interval 17.1 to 38.1	21.6 Percentage of participants Interval 12.9 to 32.7
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Progressive Disease	5.3 Percentage of participants Interval 1.5 to 13.1	8.1 Percentage of participants Interval 3.0 to 16.8

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis who received treatment in the extension period.

Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.

Outcome measures

Outcome measures
Measure	Rituximab n=63 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=62 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Number of Participants With Improved Overall Response During the Extended Treatment Period	31 Participants	32 Participants

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Complete Response	22.7 Percentage of participants Interval 13.8 to 33.8	41.9 Percentage of participants Interval 30.5 to 53.9
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Partial Response	41.3 Percentage of participants Interval 30.1 to 53.3	24.3 Percentage of participants Interval 15.1 to 35.7
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Stable Disease	26.7 Percentage of participants Interval 17.1 to 38.1	21.6 Percentage of participants Interval 12.9 to 32.7
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment Progressive Disease	5.3 Percentage of participants Interval 1.5 to 13.1	8.1 Percentage of participants Interval 3.0 to 16.8
Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment No Response Assessment	4.0 Percentage of participants Not estimable.	4.1 Percentage of participants Not estimable.

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: ITT population included all randomized participants with follicular non-Hodgkin's lymphoma at the time of diagnosis. If no PFS even occurred, PFS was censored at the date of the last tumor assessment. If no tumor assessment was available patient was censored at the date of the first study drug administration.

PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by the Investigator. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Progression-Free Survival (PFS)	772 Days Interval 425.0 to 867.0	536 Days Interval 394.0 to Upper limit was not estimable due to insufficient number of participants with events therefore the upper confidence limit of the survival curve is above 50%.

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: Participants from the ITT population (all randomized participants) with follicular non-Hodgkin's lymphoma at the time of diagnosis. If event did not occur, PFS was censored at the date of the last tumor assessment. If no tumor assessment is available patient was censored at the date of the first study drug administration.

The percentage of participants with progression, relapse, or death events from any cause as assessed by the Investigator. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Percentage of Participants With Progression-Free Survival (PFS) Events	57.7 Percentage of participants	51.4 Percentage of participants

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: ITT population included all randomized participants with follicular non-Hodgkin's lymphoma at the time of diagnosis. If no EFS event occurred, EFS was censored at the date of the last tumor assessment. If no tumor assessment is available patient was censored at the date of the first study drug administration.

Event-free survival (EFS) was defined as the time between date of randomization and the date of disease progression/relapse, death, or start of a new anti-leukemic therapy. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Event Free Survival	472.0 Days Interval 362.0 to 772.0	472.0 Days Interval 318.0 to 605.0

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Percentage of participants with Event Free Events: disease progression/relapse, death, or start of a new anti-leukemic therapy. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

Outcome measures

Outcome measures
Measure	Rituximab n=75 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=74 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Percentage of Participants With Event Free Survival (EFS) Events	64.0 Percentage of participants	63.5 Percentage of participants

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: Participants from the ITT population (all randomized participants with follicular NHL at the time of diagnosis N=75/74\] with response. Patients with no documented progression after CR or PR will be censored at the last tumor assessment. If no assessment available patients will be censored at the first study drug.

Duration of Response was defined as the date the response, either Complete Response (CR) or Partial Response (PR), was first recorded until the date of Disease Progression or death due to any cause. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease. Disease Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.

Outcome measures

Outcome measures
Measure	Rituximab n=48 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=49 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Duration of Response	809 Months Interval 412.0 to Upper limit was not estimable due to insufficient number of participants with events therefore the upper confidence limit of the survival curve is above 50%.	NA Months Interval 672.0 to Median and Upper limit was not estimable due to insufficient number of participants with events therefore the upper confidence limit of the survival curve is above 50%.

SECONDARY outcome

Timeframe: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Population: PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Blood was collected for Pharmacokinetic (PK) Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Terminal Half-Life was calculated in days.

Outcome measures

Outcome measures
Measure	Rituximab n=72 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Serum PK Parameter: Terminal Half-Life (t1/2)	41.0 days Standard Deviation 28.6	—

SECONDARY outcome

Timeframe: Day 1 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours post-infusion), Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Population: PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycles 1, 2, 3 and 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was calculated in micrograms/milliliter (μg/mL).

Outcome measures

Outcome measures
Measure	Rituximab n=78 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax) Cycle 1 (n=74)	292 μg/mL Standard Deviation 87.4	—
Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax) Cycle 2 (n=78)	448 μg/mL Standard Deviation 129	—
Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax) Cycle 3 (n=77)	561 μg/mL Standard Deviation 158	—
Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax) Cycle 4 (n=77)	692 μg/mL Standard Deviation 213	—

SECONDARY outcome

Timeframe: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Population: PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). AUClast was calculated in days\* micrograms/milliliter (μg/mL)

Outcome measures

Outcome measures
Measure	Rituximab n=77 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve (AUClast)	23400 day*μg/mL Standard Deviation 10300	—

SECONDARY outcome

Timeframe: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Population: PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). CLsst was calculated in milliliter/day (mL/day)

Outcome measures

Outcome measures
Measure	Rituximab n=72 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Serum PK Parameter: Clearance at Steady-State (CLss)	308 mL/day Standard Deviation 470	—

SECONDARY outcome

Timeframe: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Population: PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Vss was calculated in liters (L).

Outcome measures

Outcome measures
Measure	Rituximab n=72 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Serum PK Parameter: Volume of Distribution at Steady-State (Vss)	14.6 Liter Standard Deviation 9.8	—

SECONDARY outcome

Timeframe: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Population: PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). AUCtau was calculated in days\* micrograms/milliliter (μg/mL)

Outcome measures

Outcome measures
Measure	Rituximab n=77 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve Between Dosing Interval (AUCtau)	4370 day*μg/mL Standard Deviation 1340	—

SECONDARY outcome

Timeframe: Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Population: PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycles 2, 3 and 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Ctrough was calculated in micrograms/milliliter (μg/mL).

Outcome measures

Outcome measures
Measure	Rituximab n=78 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Trough Serum Concentration (Ctrough) Cycle 2 (n=78)	154 μg/mL Standard Deviation 62.7	—
Obinutuzumab Trough Serum Concentration (Ctrough) Cycle 3 (n=77)	301 μg/mL Standard Deviation 119	—
Obinutuzumab Trough Serum Concentration (Ctrough) Cycle 4 (n=75)	418 μg/mL Standard Deviation 147	—

SECONDARY outcome

Timeframe: Day 22

Population: Participants from the Safety Population, all randomized participants who received study drug, with data available for analysis.

Blood was collected and sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry at the end of the induction period. B-cell depletion was defined as a CD19 result 5 % of the Baseline value after at least one dose of study drug was administered.

Outcome measures

Outcome measures
Measure	Rituximab n=84 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=85 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Number of Participants With Peripheral Blood B-Cell Depletion	80 Participants	82 Participants

SECONDARY outcome

Timeframe: End of last dose + 6 Months Follow-Up

Population: Participants from the Safety Population, all randomized participants who received study drug, with previous B-Cell Depletion and B-Cell assessment at 6 Month Follow-up.

Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell recovery was defined as the time point when the CD-19 values return to ≥ 50% of baseline levels. The number of participants with B-cell recovery from End of Induction (treatment) Phase to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) or Recovery without PD. PD required one of the following: 50 % increase in the absolute number of circulating lymphocytes, Appearance of new palpable lymph nodes, 50 % increase in the longest diameter of any previous site of lymphadenopathy, 50 % increase in the enlargement of the liver and/or spleen or Transformation to a more aggressive histology.

Outcome measures

Outcome measures
Measure	Rituximab n=69 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=73 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Number of Participants With Peripheral Blood B-Cell Recovery Recovery with PD	0 Participants	2 Participants
Number of Participants With Peripheral Blood B-Cell Recovery Recovery without PD	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) [Includes all AEs reported 28 days after last dose and all Related SAEs regardless of time of last dose.]

Population: Safety Population included all randomized participants who received study drug.

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory result), symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. A SAE was any AE that was one of the following: fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product or considered a significant medical event by the investigator. Additional information about AEs can be found in the Adverse Event Section.

Outcome measures

Outcome measures
Measure	Rituximab n=86 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=87 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	74 Participants	83 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE	17 Participants	21 Participants

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: Safety Population included all randomized participants who received at least once dose of study drug.

Infusion Related Reactions were AEs that occurred during the infusion or within 24 hours of the infusion.

Outcome measures

Outcome measures
Measure	Rituximab n=86 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=87 Participants Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Number of Participants With Infusion Related Reactions	44 Participants	70 Participants

SECONDARY outcome

Timeframe: Day 1

Population: Participants from the Safety Population, all randomized participants who received study drug, who had samples available for HACA analysis.

Blood was collected on Day 1 and was sent to a central laboratory for analysis of human anti-chimeric antibodies (anti-rituximab antibodies) using a validated enzyme-linked immunosorbent assay (ELISA). HACA samples were not collected for participants randomized to the rituximab arm.

Outcome measures

Outcome measures
Measure	Rituximab n=86 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Number of Participants With Human Anti-Chimeric Antibodies (HACA)	1 Participants	—

SECONDARY outcome

Timeframe: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Population: Safety Population included all randomized participants who received study drug.

Blood was collected on Day 1 pre-infusion, during the safety follow-up for those patients who did not enter the Extension period and 6 months after the last infusion of the Extension Period if applicable. Blood was sent to a central laboratory and was tested for anti-obinutuzumab antibodies using a validated enzyme-linked immunosorbent assay (ELISA). HAHA samples were not collected for participants randomized to the rituximab arm.

Outcome measures

Outcome measures
Measure	Rituximab n=86 Participants Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Number of Participants With Human Anti-Human Antibodies (HAHA)	0 Participants	—

Adverse Events

Rituximab

Serious events: 13 serious events

Other events: 70 other events

Deaths: 0 deaths

Obinutuzumab

Serious events: 13 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Rituximab n=86 participants at risk Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=87 participants at risk Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Blood and lymphatic system disorders Febrile neutropenia	2.3% 2/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	2.3% 2/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Blood and lymphatic system disorders Eosinophilia	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Blood and lymphatic system disorders Neutropenia	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Pneumonia	2.3% 2/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	2.3% 2/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Cellulitis	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Herpes zoster disseminated	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Injury, poisoning and procedural complications Infusion related reaction	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	2.3% 2/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Injury, poisoning and procedural complications Fibula fracture	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Cardiac disorders Angina pectoris	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Cardiac disorders Cardio-respiratory arrest	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
General disorders Pyrexia	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Hepatobiliary disorders Hepatitis cholestatic	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Psychiatric disorders Confusional state	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Renal and urinary disorders Renal colic	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Cardiac disorders Diastolic dysfunction	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Chronic sinusitis	0.00% 0/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	1.1% 1/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Respiratory tract infection	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	0.00% 0/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.

Measure	Rituximab n=86 participants at risk Participants received 375 mg/m\^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m\^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Obinutuzumab n=87 participants at risk Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Blood and lymphatic system disorders Neutropenia	7.0% 6/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	3.4% 3/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Gastrointestinal disorders Abdominal pain upper	7.0% 6/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	2.3% 2/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Gastrointestinal disorders Diarrhoea	8.1% 7/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	8.0% 7/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Gastrointestinal disorders Nausea	8.1% 7/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	9.2% 8/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
General disorders Asthenia	5.8% 5/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	6.9% 6/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
General disorders Fatigue	19.8% 17/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	26.4% 23/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
General disorders Oedema peripheral	4.7% 4/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	6.9% 6/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
General disorders Pyrexia	10.5% 9/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	5.7% 5/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Bronchitis	3.5% 3/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	8.0% 7/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Influenza	5.8% 5/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	3.4% 3/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Nasopharyngitis	4.7% 4/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	6.9% 6/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Sinusitis	4.7% 4/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	6.9% 6/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Upper respiratory tract infection	10.5% 9/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	10.3% 9/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Injury, poisoning and procedural complications Infusion related reactions	50.0% 43/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	71.3% 62/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Metabolism and nutrition disorders Decreased appetite	3.5% 3/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	9.2% 8/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Musculoskeletal and connective tissue disorders Arthralgia	9.3% 8/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	4.6% 4/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Musculoskeletal and connective tissue disorders Back pain	3.5% 3/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	8.0% 7/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Musculoskeletal and connective tissue disorders Myalgia	2.3% 2/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	5.7% 5/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Nervous system disorders Dizziness	7.0% 6/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	4.6% 4/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Nervous system disorders Headache	8.1% 7/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	9.2% 8/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Nervous system disorders Paraesthesia	2.3% 2/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	5.7% 5/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Respiratory, thoracic and mediastinal disorders Cough	9.3% 8/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	23.0% 20/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.8% 5/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	2.3% 2/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Skin and subcutaneous tissue disorders Rash	3.5% 3/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	6.9% 6/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Vascular disorders Hypertension	8.1% 7/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	2.3% 2/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Psychiatric disorders Insomnia	1.2% 1/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	4.6% 4/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Gastrointestinal disorders Vomiting	3.5% 3/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	4.6% 4/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Rhinitis	4.7% 4/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	4.6% 4/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Infections and infestations Herpes zoster	2.3% 2/86 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.	4.6% 4/87 • First dose of study drug to 28 days past last dose of study drug (Up to 27 Months) Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.