Trial Outcomes & Findings for A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib (NCT NCT01140347)
NCT ID: NCT01140347
Last Updated: 2015-12-28
Results Overview
OS was defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up were censored on the last date the participant was known to be alive.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
565 participants
Primary outcome timeframe
Randomization to death from any cause (up to 37 months)
Results posted on
2015-12-28
Participant Flow
Participants who died due to any cause or were alive and on study at conclusion but off treatment were considered to have completed the study.
Participant milestones
| Measure |
Ramucirumab (IMC-1121B) + BSC
Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) intravenous (IV) infusion every 2 weeks.
Best supportive care (BSC): Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Overall Study
STARTED
|
283
|
282
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
277
|
276
|
|
Overall Study
COMPLETED
|
265
|
268
|
|
Overall Study
NOT COMPLETED
|
18
|
14
|
Reasons for withdrawal
| Measure |
Ramucirumab (IMC-1121B) + BSC
Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) intravenous (IV) infusion every 2 weeks.
Best supportive care (BSC): Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
5
|
6
|
|
Overall Study
Withdrawal by Subject
|
13
|
8
|
Baseline Characteristics
A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib
Baseline characteristics by cohort
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=283 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=282 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Total
n=565 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.9 years
STANDARD_DEVIATION 11.56 • n=5 Participants
|
62.5 years
STANDARD_DEVIATION 11.10 • n=7 Participants
|
62.7 years
STANDARD_DEVIATION 11.33 • n=5 Participants
|
|
Age, Customized
<65 years
|
150 participants
n=5 Participants
|
162 participants
n=7 Participants
|
312 participants
n=5 Participants
|
|
Age, Customized
≥65 years
|
133 participants
n=5 Participants
|
120 participants
n=7 Participants
|
253 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
236 Participants
n=5 Participants
|
242 Participants
n=7 Participants
|
478 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
253 Participants
n=5 Participants
|
260 Participants
n=7 Participants
|
513 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
131 Participants
n=5 Participants
|
135 Participants
n=7 Participants
|
266 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
139 Participants
n=5 Participants
|
137 Participants
n=7 Participants
|
276 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
20 participants
n=7 Participants
|
37 participants
n=5 Participants
|
|
Region of Enrollment
Portugal
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Philippines
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
33 participants
n=5 Participants
|
25 participants
n=7 Participants
|
58 participants
n=5 Participants
|
|
Region of Enrollment
Hong Kong
|
14 participants
n=5 Participants
|
10 participants
n=7 Participants
|
24 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
9 participants
n=5 Participants
|
12 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Switzerland
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
33 participants
n=5 Participants
|
18 participants
n=7 Participants
|
51 participants
n=5 Participants
|
|
Region of Enrollment
France
|
32 participants
n=5 Participants
|
27 participants
n=7 Participants
|
59 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
3 participants
n=5 Participants
|
8 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
28 participants
n=5 Participants
|
42 participants
n=7 Participants
|
70 participants
n=5 Participants
|
|
Region of Enrollment
Finland
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
11 participants
n=5 Participants
|
9 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
15 participants
n=5 Participants
|
12 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
19 participants
n=5 Participants
|
21 participants
n=7 Participants
|
40 participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
45 participants
n=5 Participants
|
48 participants
n=7 Participants
|
93 participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization to death from any cause (up to 37 months)Population: Intent-to-treat (ITT) Population: All randomized participants. Participants censored: Ramucirumab+BSC (Ram)=65, Placebo+BSC (Pl)=58.
OS was defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up were censored on the last date the participant was known to be alive.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=283 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=282 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Overall Survival (OS)
|
9.17 months
Interval 8.05 to 10.64
|
7.62 months
Interval 6.01 to 9.33
|
SECONDARY outcome
Timeframe: Randomization to PD (up to 36 months)Population: ITT Population: All randomized participants. Participants censored: Ram=43, Pl=19.
PFS was defined as time from date of randomization until date of objectively determined progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death from any cause. PD was defined as ≥20% increase in sum of diameters (SOD) of target lesions, taking as reference smallest sum on study (including baseline sum if it was smallest). Sum must show a ≥5 millimeter (mm) increase. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. In primary analysis, participants alive and without PD were censored at day of last adequate tumor assessment; progression or deaths without progression occurring immediately after ≥2 missed tumor assessments, were censored at day of the last adequate tumor assessment prior to missing assessments; participants who began new anticancer therapy were censored at day of the last adequate tumor assessment prior to start of new anticancer therapy.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=283 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=282 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Progression-Free Survival (PFS)
|
2.79 months
Interval 2.69 to 3.94
|
2.10 months
Interval 1.58 to 2.69
|
SECONDARY outcome
Timeframe: Baseline to the date of first evidence of confirmed CR or PR (up to 37 months)Population: ITT Population: All randomized participants.
ORR was defined, using RECIST v1.1 criteria, as the percentage of participants who achieved a best overall response of CR or PR. CR was defined as the disappearance of all lesions and any intratumor arterial enhancement in target lesions, the normalization of the tumor marker level and all lymph nodes short axis reduced to \<10 mm. PR was defined as ≥30% decrease in the SOD of target lesions, including the short axes of any target lymph nodes, taking as reference the baseline SOD of target lesions, no new lesions and stable nontarget lesions. Percentage of participants was calculated as: (number of participants with CR or PR / number of participants randomized) \* 100.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=283 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=282 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
|
7.1 percentage of participants
Interval 4.6 to 10.7
|
0.7 percentage of participants
Interval 0.2 to 2.5
|
SECONDARY outcome
Timeframe: Randomization to PD (up to 36 months)Population: ITT Population: All randomized participants. Participants censored: Ram=86, Pl=52.
TTP was defined as the time from randomization to the first radiographically documented PD. PD was defined, using RECIST v1.1 criteria, as ≥20% increase in SOD of target lesions, taking as reference smallest sum on study (including baseline sum if it was the smallest). Sum must show an absolute increase of ≥5 mm. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. Participants without PD were censored at the day of the last adequate tumor assessment. Progression occurred immediately after ≥2 missed tumor assessments and were censored at the day of the last adequate tumor assessment prior to the missing assessments. Participants who began new anticancer therapy were censored at the day of their last adequate tumor assessment prior to start of new anticancer therapy.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=283 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=282 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Time to Radiographic Progression (TTP)
|
3.48 months
Interval 2.76 to 4.47
|
2.63 months
Interval 1.58 to 2.76
|
SECONDARY outcome
Timeframe: Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), and end of treatment (up to 34 months)Population: Randomized participants who had FHSI-8 at baseline and the specified time points.
The FHSI-8 is a self-administered 8-item questionnaire that measures a participant's symptoms in the domains of jaundice, stomach pain/discomfort weight loss, and fatigue. Participants rated each item on a 5-point scale from 0 (not at all) to 4 (very much). Item scores were calculated as outlined in the FACIT manual. FHSI-8 total score was the sum of each item's score with a total score ranging from 0 (highly symptomatic) to 32 (asymptomatic).
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=169 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=199 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
Cycle 4 (n=166, 147)
|
-1.26 units on a scale
Standard Deviation 3.164
|
-0.81 units on a scale
Standard Deviation 4.623
|
|
Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
Cycle 10 (n=70, 45)
|
-1.28 units on a scale
Standard Deviation 3.989
|
-0.01 units on a scale
Standard Deviation 4.378
|
|
Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
Cycle 16 (n=47, 24)
|
-0.97 units on a scale
Standard Deviation 4.095
|
0.75 units on a scale
Standard Deviation 3.768
|
|
Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
End of Treatment (n=169, 199)
|
-2.44 units on a scale
Standard Deviation 5.561
|
-2.86 units on a scale
Standard Deviation 5.618
|
SECONDARY outcome
Timeframe: Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), end of treatment (up to 34 months)Population: Randomized participants who had an EQ-5D score at baseline and the specified time points.
The EQ-5D is a self-reported, 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire related to the participant's current health state. Each question was scored using a 3 level scale (no problems, some problems, or extreme problems). EQ-5D health state was defined by combining responses from each of the 5 dimensions into a weighted health-state index score according to the United Kingdom (UK) population based algorithm where 0 = death and 1 = perfect health.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=166 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=190 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score
Cycle 4 (n=166, 145)
|
-0.038 units on a scale
Standard Deviation 0.189
|
-0.046 units on a scale
Standard Deviation 0.245
|
|
Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score
Cycle 10 (n=71, 45)
|
-0.054 units on a scale
Standard Deviation 0.212
|
0.003 units on a scale
Standard Deviation 0.148
|
|
Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score
Cycle 16 (n=47, 25)
|
-0.062 units on a scale
Standard Deviation 0.214
|
-0.012 units on a scale
Standard Deviation 0.085
|
|
Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score
End of Treatment (n=166, 190)
|
-0.129 units on a scale
Standard Deviation 0.290
|
-0.144 units on a scale
Standard Deviation 0.280
|
SECONDARY outcome
Timeframe: Baseline to study completion (up to 37 months)Population: Participants who received at least 1 dose of study drug.
The number of participants with serious AEs (SAEs), other non-serious AEs and participants who died. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=277 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=276 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died
SAEs
|
123 participants
|
92 participants
|
|
Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died
Other Non-SAEs
|
254 participants
|
235 participants
|
|
Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died
Died
|
215 participants
|
220 participants
|
SECONDARY outcome
Timeframe: 1 hour following the completion of Cycle 1 (14-day cycle) infusionPopulation: Participants who received Cycle 1 of Ram and had Cmax results.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=247 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Maximum Concentration (Cmax) of Ramucirumab, Cycle 1
|
149.6 micrograms/milliliter (µg/mL)
Geometric Coefficient of Variation 36.9
|
—
|
SECONDARY outcome
Timeframe: 1 hour following completion of Cycle 4 (14-day cycles) infusionPopulation: Participants who received Cycle 4 of Ram and had Cmax results.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=140 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Cmax of Ramucirumab, Cycle 4
|
189.5 µg/mL
Geometric Coefficient of Variation 39.1
|
—
|
SECONDARY outcome
Timeframe: 1 hour following completion of Cycle 7 (14-day cycles) infusionPopulation: Participants who received Cycle 7 of Ram and had Cmax results.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=81 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Cmax of Ramucirumab, Cycle 7
|
184.4 µg/mL
Geometric Coefficient of Variation 56.3
|
—
|
SECONDARY outcome
Timeframe: Prior to treatment and 1 hour post end of infusion for Cycles 1, 4 and 7 (14-day cycles)Population: Participants who received at least 1 dose of study drug and had post-treatment ADA analysis.
Participants were considered positive for anti-ramucirumab antibodies \[anti-drug antibodies (ADA)\] if the post-treatment sample had an increase of at least 4-fold in titer from the pretreatment values. If the pretreatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence of ADA.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=241 Participants
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=231 Participants
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)]
|
10 participants
|
7 participants
|
Adverse Events
Ramucirumab (IMC-1121B) + BSC
Serious events: 124 serious events
Other events: 254 other events
Deaths: 0 deaths
Placebo + BSC
Serious events: 92 serious events
Other events: 235 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=277 participants at risk
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=276 participants at risk
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
General disorders
Generalised oedema
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
General disorders
Hernia obstructive
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/277
|
0.72%
2/276 • Number of events 2
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Cardiac disorders
Pericardial effusion
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Eye disorders
Retinal detachment
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Abdominal distension
|
0.36%
1/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
2.2%
6/277 • Number of events 7
|
3.3%
9/276 • Number of events 10
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Ascites
|
2.9%
8/277 • Number of events 8
|
1.1%
3/276 • Number of events 4
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.36%
1/277 • Number of events 2
|
0.00%
0/276
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Dysphagia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Food poisoning
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Gastric antral vascular ectasia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Gastric varices haemorrhage
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Gastroduodenitis
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
2.5%
7/277 • Number of events 7
|
0.00%
0/276
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/277
|
0.36%
1/276 • Number of events 2
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.72%
2/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Oesophageal haemorrhage
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 2
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
1.4%
4/277 • Number of events 5
|
3.6%
10/276 • Number of events 12
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.72%
2/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
Gastrointestinal disorders
Varices oesophageal
|
0.36%
1/277 • Number of events 2
|
0.00%
0/276
|
|
Gastrointestinal disorders
Vomiting
|
0.36%
1/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
General disorders
Asthenia
|
1.4%
4/277 • Number of events 5
|
0.36%
1/276 • Number of events 1
|
|
General disorders
Chills
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
General disorders
Death
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
General disorders
Extravasation
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
General disorders
Fatigue
|
0.36%
1/277 • Number of events 1
|
0.72%
2/276 • Number of events 2
|
|
General disorders
General physical health deterioration
|
3.2%
9/277 • Number of events 9
|
1.1%
3/276 • Number of events 4
|
|
General disorders
Hyperthermia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
General disorders
Malaise
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
General disorders
Multi-organ failure
|
0.72%
2/277 • Number of events 2
|
0.36%
1/276 • Number of events 2
|
|
General disorders
Non-cardiac chest pain
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
General disorders
Oedema
|
0.00%
0/277
|
0.72%
2/276 • Number of events 2
|
|
General disorders
Oedema peripheral
|
0.72%
2/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
General disorders
Pyrexia
|
2.5%
7/277 • Number of events 8
|
1.1%
3/276 • Number of events 3
|
|
General disorders
Sudden death
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Hepatobiliary disorders
Acute hepatic failure
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Hepatobiliary disorders
Bile duct stone
|
0.36%
1/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
Hepatobiliary disorders
Cholangitis
|
1.8%
5/277 • Number of events 8
|
0.36%
1/276 • Number of events 1
|
|
Hepatobiliary disorders
Cholangitis acute
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic failure
|
2.2%
6/277 • Number of events 9
|
1.8%
5/276 • Number of events 9
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Hepatobiliary disorders
Hepatorenal syndrome
|
1.4%
4/277 • Number of events 4
|
0.36%
1/276 • Number of events 1
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.36%
1/277 • Number of events 1
|
1.1%
3/276 • Number of events 3
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Hepatobiliary disorders
Jaundice
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/277
|
0.72%
2/276 • Number of events 2
|
|
Hepatobiliary disorders
Liver disorder
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Immune system disorders
Anaphylactic reaction
|
0.72%
2/277 • Number of events 2
|
0.00%
0/276
|
|
Infections and infestations
Anal abscess
|
0.72%
2/277 • Number of events 2
|
0.00%
0/276
|
|
Infections and infestations
Bacteraemia
|
0.36%
1/277 • Number of events 2
|
0.00%
0/276
|
|
Infections and infestations
Campylobacter infection
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Candida sepsis
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Device related infection
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Device related sepsis
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Infection
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Influenza
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Infections and infestations
Liver abscess
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Lobar pneumonia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Lung infection
|
0.72%
2/277 • Number of events 2
|
0.00%
0/276
|
|
Infections and infestations
Peritonitis
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Infections and infestations
Peritonitis bacterial
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Pneumonia
|
1.1%
3/277 • Number of events 3
|
1.1%
3/276 • Number of events 4
|
|
Infections and infestations
Pneumonia bacterial
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Pneumonia klebsiella
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Infections and infestations
Pulmonary sepsis
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Infections and infestations
Sepsis
|
1.1%
3/277 • Number of events 3
|
0.72%
2/276 • Number of events 3
|
|
Infections and infestations
Septic shock
|
0.00%
0/277
|
0.36%
1/276 • Number of events 2
|
|
Infections and infestations
Upper respiratory tract infection
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
1.1%
3/277 • Number of events 4
|
0.00%
0/276
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Investigations
Blood bilirubin increased
|
0.72%
2/277 • Number of events 2
|
0.00%
0/276
|
|
Investigations
Blood creatinine increased
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Investigations
General physical condition abnormal
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Investigations
Liver function test abnormal
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Metabolism and nutrition disorders
Cachexia
|
0.36%
1/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.1%
3/277 • Number of events 3
|
0.00%
0/276
|
|
Metabolism and nutrition disorders
Dehydration
|
0.72%
2/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/277
|
0.72%
2/276 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/277
|
1.4%
4/276 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.36%
1/277 • Number of events 2
|
0.00%
0/276
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liver carcinoma ruptured
|
0.72%
2/277 • Number of events 3
|
0.72%
2/276 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
8.3%
23/277 • Number of events 30
|
5.8%
16/276 • Number of events 22
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.36%
1/277 • Number of events 2
|
0.00%
0/276
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small intestine adenocarcinoma
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/277
|
1.4%
4/276 • Number of events 5
|
|
Nervous system disorders
Central nervous system lesion
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Nervous system disorders
Coma hepatic
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Nervous system disorders
Convulsion
|
0.72%
2/277 • Number of events 2
|
0.00%
0/276
|
|
Nervous system disorders
Diplegia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Nervous system disorders
Dizziness
|
0.36%
1/277 • Number of events 1
|
0.36%
1/276 • Number of events 1
|
|
Nervous system disorders
Encephalopathy
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Nervous system disorders
Hepatic encephalopathy
|
4.3%
12/277 • Number of events 16
|
0.36%
1/276 • Number of events 1
|
|
Nervous system disorders
Mental impairment
|
0.36%
1/277 • Number of events 2
|
0.00%
0/276
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Nervous system disorders
Somnolence
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Nervous system disorders
Spinal cord compression
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Nervous system disorders
Tongue biting
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
0.72%
2/277 • Number of events 4
|
0.00%
0/276
|
|
Renal and urinary disorders
Renal failure acute
|
1.1%
3/277 • Number of events 4
|
0.36%
1/276 • Number of events 1
|
|
Renal and urinary disorders
Renal impairment
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/277
|
0.36%
1/276 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.36%
1/277 • Number of events 1
|
0.72%
2/276 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.72%
2/277 • Number of events 2
|
0.36%
1/276 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.72%
2/277 • Number of events 2
|
1.1%
3/276 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.36%
1/277 • Number of events 1
|
0.72%
2/276 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
|
Vascular disorders
Deep vein thrombosis
|
0.72%
2/277 • Number of events 2
|
0.00%
0/276
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/277
|
0.36%
1/276 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.36%
1/277 • Number of events 2
|
0.00%
0/276
|
|
Vascular disorders
Shock haemorrhagic
|
0.36%
1/277 • Number of events 1
|
0.00%
0/276
|
Other adverse events
| Measure |
Ramucirumab (IMC-1121B) + BSC
n=277 participants at risk
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
Placebo + BSC
n=276 participants at risk
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.5%
29/277 • Number of events 54
|
11.2%
31/276 • Number of events 44
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.1%
14/277 • Number of events 54
|
2.5%
7/276 • Number of events 19
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.8%
16/277 • Number of events 80
|
1.4%
4/276 • Number of events 8
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.3%
48/277 • Number of events 189
|
4.3%
12/276 • Number of events 26
|
|
Gastrointestinal disorders
Abdominal distension
|
6.9%
19/277 • Number of events 27
|
10.1%
28/276 • Number of events 31
|
|
Gastrointestinal disorders
Abdominal pain
|
16.2%
45/277 • Number of events 63
|
21.0%
58/276 • Number of events 86
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.4%
26/277 • Number of events 34
|
9.1%
25/276 • Number of events 32
|
|
Gastrointestinal disorders
Ascites
|
26.0%
72/277 • Number of events 110
|
14.5%
40/276 • Number of events 47
|
|
Gastrointestinal disorders
Constipation
|
13.0%
36/277 • Number of events 39
|
12.3%
34/276 • Number of events 39
|
|
Gastrointestinal disorders
Diarrhoea
|
18.1%
50/277 • Number of events 74
|
13.8%
38/276 • Number of events 52
|
|
Gastrointestinal disorders
Gingival bleeding
|
6.5%
18/277 • Number of events 22
|
1.4%
4/276 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
18.8%
52/277 • Number of events 71
|
18.8%
52/276 • Number of events 74
|
|
Gastrointestinal disorders
Vomiting
|
10.8%
30/277 • Number of events 39
|
14.5%
40/276 • Number of events 47
|
|
General disorders
Asthenia
|
18.1%
50/277 • Number of events 80
|
13.0%
36/276 • Number of events 63
|
|
General disorders
Fatigue
|
23.8%
66/277 • Number of events 97
|
21.7%
60/276 • Number of events 99
|
|
General disorders
Oedema peripheral
|
36.1%
100/277 • Number of events 151
|
18.1%
50/276 • Number of events 58
|
|
General disorders
Pyrexia
|
15.2%
42/277 • Number of events 59
|
9.1%
25/276 • Number of events 32
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
3.6%
10/277 • Number of events 16
|
5.4%
15/276 • Number of events 32
|
|
Infections and infestations
Nasopharyngitis
|
5.4%
15/277 • Number of events 15
|
5.1%
14/276 • Number of events 16
|
|
Investigations
Alanine aminotransferase increased
|
4.7%
13/277 • Number of events 34
|
7.6%
21/276 • Number of events 33
|
|
Investigations
Aspartate aminotransferase increased
|
10.8%
30/277 • Number of events 59
|
14.1%
39/276 • Number of events 70
|
|
Investigations
Blood alkaline phosphatase increased
|
6.5%
18/277 • Number of events 40
|
5.1%
14/276 • Number of events 25
|
|
Investigations
Blood bilirubin increased
|
6.9%
19/277 • Number of events 39
|
8.7%
24/276 • Number of events 38
|
|
Metabolism and nutrition disorders
Decreased appetite
|
21.3%
59/277 • Number of events 81
|
18.1%
50/276 • Number of events 62
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
11.9%
33/277 • Number of events 66
|
5.1%
14/276 • Number of events 27
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
4.7%
13/277 • Number of events 21
|
5.4%
15/276 • Number of events 20
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.9%
19/277 • Number of events 26
|
3.6%
10/276 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
23/277 • Number of events 27
|
8.3%
23/276 • Number of events 32
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.5%
18/277 • Number of events 26
|
4.3%
12/276 • Number of events 13
|
|
Nervous system disorders
Dizziness
|
8.3%
23/277 • Number of events 25
|
5.8%
16/276 • Number of events 18
|
|
Nervous system disorders
Headache
|
19.1%
53/277 • Number of events 69
|
5.4%
15/276 • Number of events 18
|
|
Psychiatric disorders
Insomnia
|
6.9%
19/277 • Number of events 20
|
7.2%
20/276 • Number of events 20
|
|
Renal and urinary disorders
Proteinuria
|
16.6%
46/277 • Number of events 117
|
4.7%
13/276 • Number of events 18
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.8%
41/277 • Number of events 54
|
9.1%
25/276 • Number of events 29
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.4%
26/277 • Number of events 33
|
9.4%
26/276 • Number of events 33
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
13.7%
38/277 • Number of events 48
|
6.2%
17/276 • Number of events 22
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.8%
16/277 • Number of events 17
|
4.3%
12/276 • Number of events 13
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.1%
28/277 • Number of events 33
|
10.5%
29/276 • Number of events 41
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
23/277 • Number of events 27
|
4.3%
12/276 • Number of events 16
|
|
Vascular disorders
Hypertension
|
19.9%
55/277 • Number of events 104
|
7.2%
20/276 • Number of events 43
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
- Publication restrictions are in place
Restriction type: OTHER