Trial Outcomes & Findings for Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes (NCT NCT01017731)
NCT ID: NCT01017731
Last Updated: 2015-06-10
Results Overview
All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR\^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.
COMPLETED
PHASE2
68 participants
Baseline, Cycle 3 (1 cycle=21 days)
2015-06-10
Participant Flow
68 participants signed the informed consent.
Participant milestones
| Measure |
IMC-1121B (Ramucirumab)
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Overall Study
STARTED
|
68
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
66
|
|
Overall Study
COMPLETED
|
60
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
IMC-1121B (Ramucirumab)
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes
Baseline characteristics by cohort
| Measure |
IMC-1121B (Ramucirumab)
n=66 Participants
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Age, Customized
Between 18 and 65 years
|
40 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
26 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
60 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
66 participants
n=5 Participants
|
|
Ethnicity
Hispanic or Latino
|
4 participants
n=5 Participants
|
|
Ethnicity
Non-Hispanic or Latino
|
62 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Cycle 3 (1 cycle=21 days)Population: Participants who received a full study dose of ramucirumab in Cycle 3 and had at least 1 pretreatment ECG and postinfusion ECG at scheduled times as specified in the protocol.
All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR\^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.
Outcome measures
| Measure |
IMC-1121B (Ramucirumab)
n=66 Participants
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants
|
3.9132 milliseconds (msec)
Interval 1.288 to 6.5385
|
SECONDARY outcome
Timeframe: Baseline up to data cut off (approximately 105.6 weeks)Population: Safety population: participants who received any quantity of ramucirumab, regardless of their eligibility for the study.
Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.
Outcome measures
| Measure |
IMC-1121B (Ramucirumab)
n=66 Participants
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Number of Participants With Drug-Related Adverse Events (AEs)
Related TEAE
|
42 participants
|
|
Number of Participants With Drug-Related Adverse Events (AEs)
Related SAE
|
11 participants
|
|
Number of Participants With Drug-Related Adverse Events (AEs)
Related Grade 3 or higher TEAE
|
14 participants
|
|
Number of Participants With Drug-Related Adverse Events (AEs)
Related AE leading to discontinuation
|
6 participants
|
SECONDARY outcome
Timeframe: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]Population: Participants who received a full dose of ramucirumab and have evaluable Cmax data during Cycle 1.
Maximum observed concentration of IMC-1121B (ramucirumab) in serum during Cycle 1 (1 cycle=21 days).
Outcome measures
| Measure |
IMC-1121B (Ramucirumab)
n=61 Participants
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Maximum Concentration (Cmax) During Cycle 1
|
485 micrograms per milliliter (mcg/mL)
Geometric Coefficient of Variation 43
|
SECONDARY outcome
Timeframe: Approximately Week 1 (Cycle 1, Day 4)Population: No participants were analyzed.
Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Approximately Week 2 (Cycle 1, Day 8)Population: No participants were analyzed.
Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Approximately Week 3 (Cycle 1, Day 15)Population: No participants were analyzed.
Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 2 (predose and 1.25 hours postdose)Population: No participants were analyzed.
Cmax was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]Population: Participants who received a full dose of ramucirumab and have evaluable Cmax data during Cycle 3.
The maximum observed serum concentration of IMC-1121B (ramucirumab) at steady state (Cmax,ss) during Cycle 3 (1 cycle=21 days).
Outcome measures
| Measure |
IMC-1121B (Ramucirumab)
n=45 Participants
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Maximum Concentration (Cmax) During Cycle 3
|
571 micrograms per milliliter (mcg/mL)
Geometric Coefficient of Variation 41
|
SECONDARY outcome
Timeframe: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]Population: Participants who received a full dose of ramucirumab and have evaluable AUC data during Cycle 1.
The area under the concentration versus time curve from time 0 to infinity \[AUC(0-inf)\] is reported during Cycle 1 (1 cycle=21 days).
Outcome measures
| Measure |
IMC-1121B (Ramucirumab)
n=58 Participants
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Area Under Concentration (AUC) During Cycle 1
|
67400 hours*micrograms/milliliter (h*mcg/mL)
Geometric Coefficient of Variation 38
|
SECONDARY outcome
Timeframe: Approximately Week 1 (Cycle 1, Day 4)Population: No participants were analyzed.
AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Approximately Week 2 (Cycle 1, Day 8)Population: No participants were analyzed.
AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Approximately Week 3 (Cycle 1, Day 15)Population: No participants analyzed.
AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Approximately Week 1 (Cycle 2, Day 1)Population: No participants were analyzed.
AUC was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]Population: Participants who received a full dose of ramucirumab and have evaluable AUC data during Cycle 3.
The area under the concentration versus time curve over the dosing interval at steady state \[AUC(tau,ss)\] is reported during Cycle 3 (1 cycle=21 days).
Outcome measures
| Measure |
IMC-1121B (Ramucirumab)
n=38 Participants
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Area Under Concentration (AUC) During Cycle 3
|
69900 hours*micrograms/milliliter (h*mcg/mL)
Geometric Coefficient of Variation 41
|
Adverse Events
IMC-1121B (Ramucirumab)
Serious adverse events
| Measure |
IMC-1121B (Ramucirumab)
n=66 participants at risk
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
Infections and infestations
Diverticulitis
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
1.5%
1/66 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
6.1%
4/66 • Number of events 4
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
1.5%
1/66 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.0%
2/66 • Number of events 2
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
1.5%
1/66 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage
|
1.5%
1/66 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
4.5%
3/66 • Number of events 4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
1.5%
1/66 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour necrosis
|
1.5%
1/66 • Number of events 1
|
|
Nervous system disorders
Headache
|
1.5%
1/66 • Number of events 1
|
|
Psychiatric disorders
Agitation
|
1.5%
1/66 • Number of events 1
|
|
Psychiatric disorders
Mental status changes
|
1.5%
1/66 • Number of events 1
|
|
Renal and urinary disorders
Calculus urinary
|
1.5%
1/66 • Number of events 1
|
|
Renal and urinary disorders
Haematuria
|
1.5%
1/66 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.1%
6/66 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.0%
2/66 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.0%
2/66 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.5%
1/66 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
3.0%
2/66 • Number of events 2
|
|
Vascular disorders
Hypertension
|
1.5%
1/66 • Number of events 1
|
|
Blood and lymphatic system disorders
Anaemia
|
1.5%
1/66 • Number of events 1
|
|
Blood and lymphatic system disorders
Anaemia megaloblastic
|
1.5%
1/66 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
1.5%
1/66 • Number of events 1
|
|
Cardiac disorders
Cardiac arrest
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
6.1%
4/66 • Number of events 4
|
|
Gastrointestinal disorders
Ascites
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Ileus
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
3.0%
2/66 • Number of events 2
|
|
Gastrointestinal disorders
Pancreatitis
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
3.0%
2/66 • Number of events 2
|
|
General disorders
Disease progression
|
9.1%
6/66 • Number of events 9
|
|
General disorders
Infusion related reaction
|
1.5%
1/66 • Number of events 1
|
|
General disorders
Oedema peripheral
|
1.5%
1/66 • Number of events 1
|
|
Hepatobiliary disorders
Bile duct obstruction
|
1.5%
1/66 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic failure
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Clostridial infection
|
1.5%
1/66 • Number of events 1
|
Other adverse events
| Measure |
IMC-1121B (Ramucirumab)
n=66 participants at risk
Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.
Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.
Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.
|
|---|---|
|
General disorders
Asthenia
|
10.6%
7/66 • Number of events 7
|
|
General disorders
Chills
|
13.6%
9/66 • Number of events 9
|
|
General disorders
Fatigue
|
31.8%
21/66 • Number of events 27
|
|
General disorders
Oedema peripheral
|
16.7%
11/66 • Number of events 19
|
|
Blood and lymphatic system disorders
Anaemia
|
6.1%
4/66 • Number of events 6
|
|
Endocrine disorders
Hypothyroidism
|
6.1%
4/66 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal distension
|
6.1%
4/66 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal pain
|
24.2%
16/66 • Number of events 18
|
|
Gastrointestinal disorders
Abdominal pain lower
|
7.6%
5/66 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
15.2%
10/66 • Number of events 10
|
|
Gastrointestinal disorders
Diarrhoea
|
24.2%
16/66 • Number of events 21
|
|
Gastrointestinal disorders
Nausea
|
31.8%
21/66 • Number of events 36
|
|
Gastrointestinal disorders
Vomiting
|
24.2%
16/66 • Number of events 22
|
|
General disorders
Pyrexia
|
15.2%
10/66 • Number of events 11
|
|
Immune system disorders
Seasonal allergy
|
6.1%
4/66 • Number of events 4
|
|
Investigations
Blood creatinine increased
|
6.1%
4/66 • Number of events 9
|
|
Metabolism and nutrition disorders
Abnormal loss of weight
|
12.1%
8/66 • Number of events 11
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
22/66 • Number of events 24
|
|
Metabolism and nutrition disorders
Dehydration
|
13.6%
9/66 • Number of events 10
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.1%
4/66 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.1%
8/66 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.6%
5/66 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.6%
5/66 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.1%
4/66 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.1%
4/66 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.1%
6/66 • Number of events 10
|
|
Nervous system disorders
Dizziness
|
15.2%
10/66 • Number of events 12
|
|
Nervous system disorders
Headache
|
30.3%
20/66 • Number of events 29
|
|
Psychiatric disorders
Anxiety
|
6.1%
4/66 • Number of events 4
|
|
Psychiatric disorders
Depression
|
10.6%
7/66 • Number of events 8
|
|
Psychiatric disorders
Insomnia
|
7.6%
5/66 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.2%
14/66 • Number of events 17
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
6.1%
4/66 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
27.3%
18/66 • Number of events 19
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
7.6%
5/66 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.6%
7/66 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.6%
5/66 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.1%
4/66 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.1%
4/66 • Number of events 4
|
|
Vascular disorders
Hypertension
|
13.6%
9/66 • Number of events 11
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
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