Trial Outcomes & Findings for A Dose-Escalating Study of Obinutuzumab in Patients With B-lymphocyte Antigen (CD20+) Malignant Disease (GAUGUIN) (NCT NCT00517530)
NCT ID: NCT00517530
Last Updated: 2016-10-11
Results Overview
Dose-limiting toxicities were defined as obinutuzumab-related adverse events occurring within the first 28 days of each administration of obinutuzumab, with the exception of B-cell depletion and lymphopenia which are expected outcomes of treatment with obinutuzumab.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
134 participants
Primary outcome timeframe
Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)
Results posted on
2016-10-11
Participant Flow
Different patients were recruited into Phase I and Phase II, and analyzed separately based on their disease. In this adaptive trial design, some of those same patients were included in follow-up even if they did not complete treatment, and 13 who had initially responded to treatment but subsequently progressed were retreated.
Participant milestones
| Measure |
50-2000 mg Phase I, NHL
Obinutuzumab intravenous infusion
|
400-2000 mg Phase I, CLL
Obinutuzumab intravenous infusion
|
400/400 mg - Phase II, iNHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase II, iNHL
Obinutuzumab intravenous infusion
|
400/400 mg - Phase II, aNHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase II, aNHL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase II, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
21
|
13
|
18
|
22
|
21
|
19
|
20
|
|
Overall Study
Completed Treatment
|
11
|
13
|
13
|
18
|
9
|
9
|
13
|
|
Overall Study
Started Follow-up
|
20
|
13
|
17
|
21
|
17
|
16
|
19
|
|
Overall Study
Completed Follow-up
|
2
|
0
|
0
|
1
|
0
|
0
|
1
|
|
Overall Study
Retreated Population
|
2
|
2
|
1
|
4
|
2
|
2
|
0
|
|
Overall Study
COMPLETED
|
2
|
0
|
0
|
1
|
1
|
0
|
1
|
|
Overall Study
NOT COMPLETED
|
19
|
13
|
18
|
21
|
20
|
19
|
19
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Dose-Escalating Study of Obinutuzumab in Patients With B-lymphocyte Antigen (CD20+) Malignant Disease (GAUGUIN)
Baseline characteristics by cohort
| Measure |
50-2000 mg Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
400-2000 mg Phase I, CLL
n=13 Participants
Obinutuzumab intravenous infusion
|
400/400 mg - Phase II, iNHL
n=18 Participants
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase II, iNHL
n=22 Participants
Obinutuzumab intravenous infusion
|
400/400 mg - Phase II, aNHL
n=21 Participants
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase II, aNHL
n=19 Participants
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase II, CLL
n=20 Participants
Obinutuzumab intravenous infusion
|
Total
n=134 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=6 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
11 Participants
n=115 Participants
|
70 Participants
n=6 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
12 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
64 Participants
n=6 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
5 Participants
n=10 Participants
|
8 Participants
n=115 Participants
|
52 Participants
n=6 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
14 Participants
n=10 Participants
|
12 Participants
n=115 Participants
|
82 Participants
n=6 Participants
|
PRIMARY outcome
Timeframe: Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)Population: Safety population: All enrolled participants in Phase I, who had received at least 1 dose of obinutuzumab by 6 months.
Dose-limiting toxicities were defined as obinutuzumab-related adverse events occurring within the first 28 days of each administration of obinutuzumab, with the exception of B-cell depletion and lymphopenia which are expected outcomes of treatment with obinutuzumab.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
n=3 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
n=3 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
n=4 Participants
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
n=3 Participants
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
PRIMARY outcome
Timeframe: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)Population: Safety population: All enrolled participants in Phase II, who had received at least 1 dose of obinutuzumab.
Best overall response (BOR) was defined as the percentage of participants with a complete response (CR) or partial response (PR)
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=18 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=22 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=19 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
n=20 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants With Best Overall Response in Phase II of the Study
|
33.3 percentage of participants
|
63.6 percentage of participants
|
23.8 percentage of participants
|
36.8 percentage of participants
|
30.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)A complete response was defined as the disappearance of all evidence of disease (NHL) and symptoms; normalization of biochemical abnormalities (NHL); regression of lymph nodes and nodal masses to normal size; decrease of nodes in the sum of the products of the greatest diameters (SPD); regression in size of the spleen and/or liver, should not be palpable, and disappearance of nodules related to lymphoma (CLL). Complete/unconfirmed (CRu) response includes NHL patients with one or more of the following: 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the SPD; 2) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). Complete Response with Incomplete Bone Marrow Recovery (CRi) was measured only in patients with CLL.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=18 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=22 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=19 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
n=20 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study
CR
|
5.6 percentage of participants
|
13.6 percentage of participants
|
9.5 percentage of participants
|
15.8 percentage of participants
|
5.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study
CRu
|
5.6 percentage of participants
|
9.1 percentage of participants
|
4.8 percentage of participants
|
0.0 percentage of participants
|
NA percentage of participants
CRu was measured only in participants with NHL
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study
CRi
|
NA percentage of participants
CRi was measured only in participants with CLL
|
NA percentage of participants
CRi was measured only in participants with CLL
|
NA percentage of participants
CRi was measured only in participants with CLL
|
NA percentage of participants
CRi was measured only in participants with CLL
|
0.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)A PR was defined as a \>=50% decrease in SPD of the 6 largest nodes or nodal masses; no increase in size of other nodes, liver, or spleen; regression of splenic and hepatic nodules by \>=50% in their SPD or, for single nodules, in the long axis (CLL only); and no new disease sites.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=18 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=22 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=19 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
n=20 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants With Partial Response (PR) in Phase II of the Study
|
22.2 percentage of participants
|
40.9 percentage of participants
|
9.5 percentage of participants
|
21.1 percentage of participants
|
25.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)Population: Safety population: All enrolled participants in Phase II, who had received at least 1 dose of obinutuzumab.
PFS was defined as the time from start of treatment to disease progression (PD) or death due to any cause, whichever occurred first. For non-Hodgkin's lymphoma participants, PD was defined as \>= 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for participants with a partial response or non-responders or the appearance of any new lesion during or at the end of therapy. For chronic lymphocytic leukemia participants, PD was defined as: (1) A \>= 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules); a lymph node with a short axis of \< 1.0 cm must increase by \>= 50% and to a size of 1.5×1.5 cm or \> 1.5 cm in the longest axis. (2) Appearance of any new lesion \> 1 cm in the short axis. (4) A new site that is positron emission tomography (PET)-positive with histological confirmation.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=18 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=22 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=19 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
n=20 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression-free Survival (PFS) in Phase II of the Study
|
182 days
Interval 106.0 to 526.0
|
361 days
Interval 343.0 to 678.0
|
78 days
Interval 42.0 to 260.0
|
83 days
Interval 43.0 to 339.0
|
324 days
Interval 217.0 to 357.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)Population: Safety population: All enrolled participants in Phase II, who had received at least 1 dose of obinutuzumab. Data reported for each disease cohort.
Duration of complete response was defined as the time from the first complete or partial response until disease progression (PD) or death, whichever occurred first. For non-Hodgkin's lymphoma participants, PD was defined as \>= 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for participants with a partial response or non-responders or the appearance of any new lesion during or at the end of therapy. For chronic lymphocytic leukemia participants, PD was defined as: (1) A \>= 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules); a lymph node with a short axis of \< 1.0 cm must increase by \>= 50% and to a size of 1.5×1.5 cm or \> 1.5 cm in the longest axis. (2) Appearance of any new lesion \> 1 cm in the short axis. (4) A new site that is PET-positive with histological confirmation.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=20 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=12 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=6 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Response by Disease Type in Phase II of the Study
|
523 days
Interval 23.0 to 952.0
|
298 days
Interval 95.0 to 929.0
|
272.5 days
Interval 23.0 to 794.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)EFS is defined as the time from start of treatment to disease progression/relapse, death or, in case of early withdrawal from the treatment period, the (end) date of last dose, whatever comes first.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=18 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=22 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=19 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
n=20 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Participants With Event-Free Survival (EFS) in Phase II of the Study
|
5 participants
|
6 participants
|
2 participants
|
3 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: by the end of Phase II (within 3 years, 4 months)Population: Participants analyzed include those with B-cell depletion at the end of treatment (N), with assessments (n) at each time point.
B-cell depletion was defined in two ways: definition 1 - decrease below 5% baseline level and definition 2 - decrease below 0.04 x 109/L. B-cell recovery was defined in two ways: definition 1 - return to at least 50% of baseline level and definition 2 - return to at least 0.08 x 109/L.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=16 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=21 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=19 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
n=16 Participants
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
after 24 months (n=3,4,1,2,0)
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
within 6 months (n=11,19,11,12,13)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
within 9 months (n=8,17,6,5,10)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
within 12 months (n=5,16,4,5,9)
|
0 participants
|
2 participants
|
1 participants
|
0 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
within 18 months (n=4,13,3,3,8)
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
within 24 months (n=3,10,2,3,5)
|
2 participants
|
2 participants
|
1 participants
|
0 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: by Cutoff Date: 25 November 2013 (within 4 years, 2 months)Population: Retreated participants
Patients who might benefit from retreatment were allowed to be treated again at the request of the investigator.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=13 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Retreated Participants With Response
Best overall response
|
62 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Retreated Participants With Response
Complete response
|
23 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Retreated Participants With Response
Partial response
|
38 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)Population: Pharmacokinetics (PK)- evaluable population at the given dose (e.g., 3 or more participants at any of the given time points). Other doses did not have a PK-evaluable population, so were not included in the table of results. Due to the limited sampling schedule derived PK parameters could not be accurately obtained during Cycle 1 and Cycle 8.
Obinutuzumab serum pharmacokinetic (PK) parameters in NHL participants following ascending doses.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=4 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=6 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=6 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=6 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Obinutuzumab in NHL Participants
Cycle 1 Day 8 (n=0,4,6,6)
|
NA µm/ml*day
Geometric Coefficient of Variation NA
n=0
|
367 µm/ml*day
Geometric Coefficient of Variation 24.2
|
449 µm/ml*day
Geometric Coefficient of Variation 26.4
|
714 µm/ml*day
Geometric Coefficient of Variation 28.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Obinutuzumab in NHL Participants
Cycle 1 Day 1 (n=4,6,6,0)
|
134 µm/ml*day
Geometric Coefficient of Variation 27.1
|
234 µm/ml*day
Geometric Coefficient of Variation 63.1
|
307 µm/ml*day
Geometric Coefficient of Variation 30.6
|
NA µm/ml*day
Geometric Coefficient of Variation NA
n=0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Obinutuzumab in NHL Participants
Cycle 8 (n=0,5,5,5)
|
NA µm/ml*day
Geometric Coefficient of Variation NA
n=0
|
698 µm/ml*day
Geometric Coefficient of Variation 65.4
|
1070 µm/ml*day
Geometric Coefficient of Variation 62.6
|
1380 µm/ml*day
Geometric Coefficient of Variation 66.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of Cycle 1Population: Pharmacokinetics (PK)- evaluable population at the given dose (e.g., 3 or more participants). Other doses did not have a PK-evaluable population, so were not included in the table of results. Due to the limited sampling schedule derived PK parameters could not be accurately obtained during Cycle 1 and Cycle 8.
Blood samples were taken on Day 1 (pre-infusion, end of infusion, 3-6 hours post-infusion) of Cycle 1. Nonlinear mixed-effects modeling (with NONMEM software) was used to analyze the pooled samples for dose-concentration-time data of obinutuzumab.
Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=4 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=6 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=6 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve of Obinutuzumab Administered on Day 1 of Cycle 1 in Phase I of the Study
|
459 µm/ml*day
Geometric Coefficient of Variation 64.7
|
993 µm/ml*day
Geometric Coefficient of Variation 30.5
|
1057 µm/ml*day
Geometric Coefficient of Variation 60.5
|
146 µm/ml*day
Geometric Coefficient of Variation 49.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)Outcome measures
| Measure |
50/100 mg - Phase I, NHL
n=3 Participants
Obinutuzumab intravenous infusion
|
100/200 mg - Phase I, NHL
n=4 Participants
Obinutuzumab intravenous infusion
|
200/400 mg - Phase I, NHL
n=4 Participants
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, NHL
n=4 Participants
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
1600/800 mg - Phase I, NHL
Obinutuzumab intravenous infusion
|
400/800 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
800/1200 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1200/2000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
1000/1000 mg - Phase I, CLL
Obinutuzumab intravenous infusion
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Obinutuzumab in CLL Patients
Cycle 1 Day 1 (n=3,3,3,0)
|
216 micrograms/mL
Geometric Coefficient of Variation 34.1
|
210 micrograms/mL
Geometric Coefficient of Variation 74.0
|
307 micrograms/mL
Geometric Coefficient of Variation 21.4
|
NA micrograms/mL
Geometric Coefficient of Variation NA
n=0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Obinutuzumab in CLL Patients
Cycle 1 Day 8 (n=0,0,3,3)
|
NA micrograms/mL
Geometric Coefficient of Variation NA
n=0
|
NA micrograms/mL
Geometric Coefficient of Variation NA
n=0
|
437 micrograms/mL
Geometric Coefficient of Variation 11.8
|
735 micrograms/mL
Geometric Coefficient of Variation 9.79
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Obinutuzumab in CLL Patients
Cycle 8 (n=3,3,3,4)
|
485 micrograms/mL
Geometric Coefficient of Variation 48.1
|
573 micrograms/mL
Geometric Coefficient of Variation 73.2
|
741 micrograms/mL
Geometric Coefficient of Variation 32.8
|
1730 micrograms/mL
Geometric Coefficient of Variation 32.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Safety Population
Serious events: 46 serious events
Other events: 123 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Safety Population
n=134 participants at risk
Safety-Evaluable Participants
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.5%
2/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Aplasia pure red cell
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.7%
5/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.5%
2/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Cardiac disorders
Acute coronary syndrome
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Cardiac disorders
Bradycardia
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Cardiac disorders
Cardiac failure
|
1.5%
2/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Cardiac disorders
Cardiorespiratory arrest
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Cardiac disorders
Pericarditis
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.5%
2/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Duodenal ulcer perforation
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
General disorders
Multi-organ failure
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
General disorders
Pyrexia
|
3.0%
4/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Bacteraemia
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Bacterial infection
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Bronchitis
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Clostridium difficile infection
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Colonic abscess
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Gingivitis
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Haemophilus infection
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Herpes zoster
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Lung infection
|
1.5%
2/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Pneumococcal infection
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Pneumococcal sepsis
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Septic shock
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Streptococcal infection
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
6.0%
8/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Injury, poisoning and procedural complications
Tooth avulsion
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Metabolism and nutrition disorders
Tumour lysis sydrome
|
3.0%
4/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal adenocarcinoma
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Nervous system disorders
Carotid artery stenosis
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Nervous system disorders
Sciatica
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Psychiatric disorders
Suicide attempt
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Renal and urinary disorders
Renal colic
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Vascular disorders
Hypertension
|
0.75%
1/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
Other adverse events
| Measure |
Safety Population
n=134 participants at risk
Safety-Evaluable Participants
|
|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
14.2%
19/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Anaemia
|
13.4%
18/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Neutropenia
|
13.4%
18/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.2%
15/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Diarrhoea
|
17.2%
23/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Nausea
|
9.0%
12/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Constipation
|
8.2%
11/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
9/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
General disorders
Asthenia
|
26.1%
35/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
General disorders
Pyrexia
|
9.7%
13/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
General disorders
Oedema peripheral
|
9.0%
12/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
General disorders
Fatigue
|
5.2%
7/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Bronchitis
|
11.2%
15/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Infections and infestations
Nasopharyngitis
|
11.2%
15/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
79.9%
107/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Investigations
Weight decreased
|
7.5%
10/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.0%
8/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.0%
8/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.0%
8/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.2%
7/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Nervous system disorders
Headache
|
6.0%
8/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Nervous system disorders
Insomnia
|
7.5%
10/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.2%
19/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.7%
9/134 • Through final cut off in November 2013
For frequency counts by preferred term, multiple occurrences of the same adverse event (AE) in an individual are counted only once.
|
Additional Information
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