A Study of Ramucirumab (IMC-1121B) and Paclitaxel in Participants With Solid Tumors
Study Details
Study Description
Brief Summary
The purpose of this study is to investigate whether there are no clinically significant pharmacokinetic effects of concomitant ramucirumab (IMC-1121B) on paclitaxel by investigating the pharmacokinetics (PK) of each in participants with advanced malignant solid tumors.
Part A of this study will investigate the potential of concomitant ramucirumab (IMC-1121B) to affect the pharmacokinetics of paclitaxel. Part B of this study will investigate the pharmacokinetics of ramucirumab (IMC-1121B) as monotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A: ramucirumab (IMC-1121B) and paclitaxel Experimental: Part A: ramucirumab (IMC-1121B) and paclitaxel Cycle 1: paclitaxel administered on Day 1 of 2-week cycle. Cycle 2 and beyond : ramucirumab (IMC-1121B) administered on Day 1 and Day 15, paclitaxel administered on Day 1, Day 8 and Day 15 of 4-week cycle. |
Biological: ramucirumab (IMC-1121B)
ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1and Day 15 of each 4-week cycle, unless otherwise specified.
Other Names:
Drug: paclitaxel
paclitaxel 80 milligrams/square meter (mg/m²) intravenous infusion, administered on Days 1, 8 and 15 of each 4-week cycle, unless otherwise specified.
|
| Experimental: Part B: ramucirumab (IMC-1121B) and paclitaxel Cycle 1: ramucirumab (IMC-1121B) administered as monotherapy on Day 1 of 3-week cycle. Cycle 2 and beyond: ramucirumab (IMC-1121B) administered on Day 1 and Day 15, paclitaxel administered on Day 1, Day 8 and Day 15 of 4- week cycle. *After Cycle 1 (mandatory pharmacokinetic phase) is completed, participants may continue to receive ramucirumab (IMC-1121B) monotherapy or combination therapy with paclitaxel as described in Part A. |
Biological: ramucirumab (IMC-1121B)
ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1and Day 15 of each 4-week cycle, unless otherwise specified.
Other Names:
Drug: paclitaxel
paclitaxel 80 milligrams/square meter (mg/m²) intravenous infusion, administered on Days 1, 8 and 15 of each 4-week cycle, unless otherwise specified.
|
Outcome Measures
Primary Outcome Measures
- Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 1 [Cycle 1: 0, 1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion]
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
- Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 2 [Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion]
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
- Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 1 [Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion]
Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
- Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 2 [Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion]
Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
- Part B: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] as Monotherapy [Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72,168, 264, 336, 408, and 504 hours post ramucirumab infusion]
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.
Secondary Outcome Measures
- Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Paclitaxel [Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion]
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.
- Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Paclitaxel [Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion]
Dose-normalized Cmax was calculated from Cmax divided by the dose.
- Part A: Immunogenicity of Ramucirumab in Combination With Paclitaxel - Number of Participants With Anti-Ramucirumab Antibodies [-1 hour on Day 1 of Cycle 2, and 30 days after last dose of study drug]
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.
- Part B: Immunogenicity of Ramucirumab as Monotherapy - Number of Participants With Anti-Ramucirumab Antibodies [0 hour on Day 1 of Cycle 1, and 30 days after last dose of study drug]
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has histologic or cytologic documentation of a malignant solid tumor
-
Has an advanced solid tumor that is refractory to standard therapy or for which no standard therapy is available
-
Part A only: Has had 0-1 prior taxane-containing treatment regimens (including taxane monotherapy), which must have been completed at least 6 months before the first dose of study medication (prior bevacizumab is allowed)
-
Part B only: Prior bevacizumab- and taxane-containing treatment regimens (including taxane monotherapy) are allowed, provided these regimens have been completed at least 6 months before the first dose of study medication
-
Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy, which must not have exceeded Grade 1, by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0)
-
Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 - 2
-
Has adequate hematologic function. Blood transfusion is allowed but must be completed 48 hours before study drug administration
-
Has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal [ULN], aspartate transaminase [AST] and alanine transaminase [ALT] ≤ 1.5 x ULN
-
Has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN, the calculated creatinine clearance (CrCl) should be ≥ 40 milliliter/minute (mL/min)
-
Urinary protein is <2+ on dipstick or routine urinalysis (UA)
-
Must have adequate coagulation function as defined by an international normalized ratio (INR) of ≤ 1.5 and a partial thromboplastin time (PTT) or an activated PTT (aPTT) ≤ 1.5 x ULN
-
Eligible participants of reproductive potential agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication
Exclusion Criteria:
-
Is receiving concomitant therapy with clinically relevant inhibitors or inducers of cytochrome P450, CYP2C8, CYP3AY and/or isoenzymes
-
Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
-
Has received a monoclonal antibody within 42 days prior to first dose of study medication
-
Has received radiotherapy within 14 days prior to first dose of study medication
-
Has received cytotoxic chemotherapy within 21 days (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study medication
-
Has a cardiac left ventricular ejection fraction (LVEF) not within institutional limits of normal on a multigated acquisition scan (MUGA) or echocardiogram
-
Is receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, targeted or other investigational anticancer therapy
-
Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents. Aspirin use at doses up to 325 milligrams/day (mg/day) and analgesic agents with no or low bleeding risk are permitted
-
Has a history of uncontrolled hereditary or acquired bleeding or thromboembolic disorders
-
Has experienced any arterial thromboembolic event, including myocardial infarction (MI), unstable angina stroke or transient ischemic attack (TIA), within 6 months prior to first dose of study medication
-
Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to first dose of study medication
-
Has experienced a Grade 3 or 4 hemorrhagic event within 3 months prior to first dose of study medication
-
Has experienced peripheral neuropathy ≥ Grade 2 at any time prior to study entry
-
Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
-
History of gastrointestinal perforation and / or fistulae within 6 months prior to randomization
-
Has an ongoing or active infection requiring treatment with intravenous antibiotics
-
Has a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to first dose of study medication
-
Has uncontrolled hypertension
-
Has symptomatic congestive heart failure
-
Has known brain or leptomeningeal disease
-
Has known positive status for human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related illness
-
Has known active drug or alcohol abuse that would affect participant's ability to comply with study treatment
-
Has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
-
Has had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study medication
-
Has an elective or planned major surgery during the course of the trial
-
If a primary cancer is non-small-cell lung cancer (NSCLC), participant has intratumor cavitation, radiologically documented evidence of major blood vessel invasion or encasement by cancer, or proximity of cancer to major airways
-
Has received prior ramucirumab (IMC-1121B) therapy
-
The participant has:
-
cirrhosis at a level of Child-Pugh B (or worse)
-
cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ImClone Investigational Site | Ann Arbor | Michigan | United States | 48109 |
| 2 | ImClone Investigational Site | Detroit | Michigan | United States | 48202 |
| 3 | ImClone Investigational Site | New Brunswick | New Jersey | United States | 08901 |
| 4 | ImClone Investigational Site | Cleveland | Ohio | United States | 44195 |
| 5 | ImClone Investigational Site | Philadelphia | Pennsylvania | United States | 19111 |
| 6 | ImClone Investigational Site | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 14432
- I4T-IE-JVCA
- CP12-1032
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part A: Paclitaxel and Ramucirumab | Part B: Ramucirumab With or Without Paclitaxel |
|---|---|---|
| Arm/Group Description | Cycle 1: paclitaxel 80 milligrams/square meter (mg/m²) administered on Day 1 of 2-week cycle. Cycle 2 and beyond: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. | Cycle 1: ramucirumab (IMC-1121B) 8 mg/kg administered as monotherapy on Day 1 of 3-week cycle. Cycle 2 and beyond: ramucirumab (IMC-1121B) 8 mg/kg administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. *After Cycle 1 (mandatory pharmacokinetic phase) is completed, participants may continue to receive ramucirumab (IMC-1121B) monotherapy or combination therapy with paclitaxel as described in Part A. |
| Period Title: Overall Study | ||
| STARTED | 24 | 16 |
| Received at Least 1 Dose of Study Drug | 24 | 16 |
| Cycle 1 | 24 | 16 |
| Cycle 2 | 21 | 15 |
| Drug-Drug Interaction Population | 21 | 0 |
| COMPLETED | 0 | 2 |
| NOT COMPLETED | 24 | 14 |
Baseline Characteristics
| Arm/Group Title | Part A: Paclitaxel and Ramucirumab | Part B: Ramucirumab With or Without Paclitaxel | Total |
|---|---|---|---|
| Arm/Group Description | Cycle 1: paclitaxel 80 milligrams/square meter (mg/m²) administered on Day 1 of 2-week cycle. Cycle 2 and beyond: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. | Cycle 1: ramucirumab (IMC-1121B) 8 mg/kg administered as monotherapy on Day 1 of 3-week cycle. Cycle 2 and beyond: ramucirumab (IMC-1121B) 8 mg/kg administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. *After Cycle 1 (mandatory pharmacokinetic phase) is completed, participants may continue to receive ramucirumab (IMC-1121B) monotherapy or combination therapy with paclitaxel as described in Part A. | Total of all reporting groups |
| Overall Participants | 24 | 16 | 40 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
14
58.3%
|
10
62.5%
|
24
60%
|
| >=65 years |
10
41.7%
|
6
37.5%
|
16
40%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
13
54.2%
|
9
56.3%
|
22
55%
|
| Male |
11
45.8%
|
7
43.8%
|
18
45%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
4.2%
|
0
0%
|
1
2.5%
|
| Not Hispanic or Latino |
23
95.8%
|
16
100%
|
39
97.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
4.2%
|
1
6.3%
|
2
5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
22
91.7%
|
15
93.8%
|
37
92.5%
|
| More than one race |
1
4.2%
|
0
0%
|
1
2.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
24
100%
|
16
100%
|
40
100%
|
Outcome Measures
| Title | Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 1 |
|---|---|
| Description | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error. |
| Time Frame | Cycle 1: 0, 1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Part A Cycle 1 and had sufficient concentration data to calculate paclitaxel AUC(0-∞). |
| Arm/Group Title | Part A: Paclitaxel Alone (Cycle 1) |
|---|---|
| Arm/Group Description | Cycle 1: paclitaxel 80 milligrams/square meter (mg/m²) administered on Day 1 of 2-week cycle. |
| Measure Participants | 19 |
| Least Squares Mean (90% Confidence Interval) [nanograms*hour/milliliter/milligram] |
29
|
| Title | Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 2 |
|---|---|
| Description | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error. |
| Time Frame | Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Part A Cycle 2 and had sufficient concentration data to calculate paclitaxel AUC(0-∞). |
| Arm/Group Title | Part A: Paclitaxel + Ramucirumab (Cycle 2) |
|---|---|
| Arm/Group Description | Cycle 2: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. |
| Measure Participants | 17 |
| Least Squares Mean (90% Confidence Interval) [nanograms*hour/milliliter/milligram] |
31.67
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Paclitaxel Alone (Cycle 1) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geo LS means |
| Estimated Value | 1.09 | |
| Confidence Interval |
(2-Sided) 90% 0.93 to 1.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 1 |
|---|---|
| Description | Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error. |
| Time Frame | Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Part A Cycle 1 and had sufficient concentration data to calculate paclitaxel cmax. |
| Arm/Group Title | Part A: Paclitaxel Alone (Cycle 1) |
|---|---|
| Arm/Group Description | Cycle 1: paclitaxel 80 milligrams/square meter (mg/m²) administered on Day 1 of 2-week cycle. |
| Measure Participants | 21 |
| Least Squares Mean (90% Confidence Interval) [nanograms/milliliter/milligram] |
18.84
|
| Title | Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 2 |
|---|---|
| Description | Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error. |
| Time Frame | Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Part A Cycle 2 and had sufficient concentration data to calculate paclitaxel cmax. |
| Arm/Group Title | Part A: Paclitaxel + Ramucirumab (Cycle 2) |
|---|---|
| Arm/Group Description | Cycle 2: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. |
| Measure Participants | 20 |
| Least Squares Mean (90% Confidence Interval) [nanograms/milliliter/milligram] |
18.30
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Paclitaxel Alone (Cycle 1) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geo LS means |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 90% 0.83 to 1.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part B: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] as Monotherapy |
|---|---|
| Description | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. |
| Time Frame | Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72,168, 264, 336, 408, and 504 hours post ramucirumab infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received ramucirumab and had sufficient concentration data to calculate ramucirumab AUC(0-∞) in Cycle 1 of Part B. |
| Arm/Group Title | Part B: Ramucirumab Alone (Cycle 1) |
|---|---|
| Arm/Group Description | Cycle 1: ramucirumab (IMC-1121B) 8 mg/kg administered as monotherapy on Day 1 of 3-week cycle. |
| Measure Participants | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms*hour/milliliter/milligram] |
55.3
(27)
|
| Title | Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Paclitaxel |
|---|---|
| Description | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. |
| Time Frame | Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received ramucirumab and paclitaxel and had sufficient concentration data to calculate ramucirumab AUC(0-∞) in Cycle 2 of Part A. |
| Arm/Group Title | Part A: Paclitaxel + Ramucirumab (Cycle 2) |
|---|---|
| Arm/Group Description | Cycle 2: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. |
| Measure Participants | 13 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms*hour/milliliters/milligram] |
55.4
(27)
|
| Title | Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Paclitaxel |
|---|---|
| Description | Dose-normalized Cmax was calculated from Cmax divided by the dose. |
| Time Frame | Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received ramucirumab and paclitaxel and had sufficient concentration data to calculate ramucirumab Cmax in Cycle 2 of Part A. |
| Arm/Group Title | Part A: Paclitaxel + Ramucirumab (Cycle 2) |
|---|---|
| Arm/Group Description | Cycle 2: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. |
| Measure Participants | 21 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms/milliliter/milligram] |
0.384
(31)
|
| Title | Part A: Immunogenicity of Ramucirumab in Combination With Paclitaxel - Number of Participants With Anti-Ramucirumab Antibodies |
|---|---|
| Description | Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline. |
| Time Frame | -1 hour on Day 1 of Cycle 2, and 30 days after last dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Part A Cycle 2, who received ramucirumab and paclitaxel and had data for anti-ramucirumab antibodies. |
| Arm/Group Title | Part A: Paclitaxel and Ramucirumab (Cycle 2) |
|---|---|
| Arm/Group Description | Cycle 2: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. |
| Measure Participants | 10 |
| Count of Participants [Participants] |
0
0%
|
| Title | Part B: Immunogenicity of Ramucirumab as Monotherapy - Number of Participants With Anti-Ramucirumab Antibodies |
|---|---|
| Description | Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline. |
| Time Frame | 0 hour on Day 1 of Cycle 1, and 30 days after last dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Part B cycle 1, who received ramucirumab and had data for anti-ramucirumab antibodies. |
| Arm/Group Title | Part B: Ramucirumab Alone (Cycle 1) |
|---|---|
| Arm/Group Description | Cycle 1: ramucirumab (IMC-1121B) 8 mg/kg administered as monotherapy on Day 1 of 3-week cycle. |
| Measure Participants | 1 |
| Count of Participants [Participants] |
0
0%
|
Adverse Events
| Time Frame | Baseline, up to 8 years | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one dose of study drug. | |||||||
| Arm/Group Title | Part A: Paclitaxel Alone (Cycle 1) | Part A: Paclitaxel + Ramucirumab (Cycle 2) | Part B: Ramucirumab Alone (Cycle 1) | Part B: Ramucirumab + Paclitaxel (Cycle 2) | ||||
| Arm/Group Description | Cycle 1: paclitaxel 80 milligrams/square meter (mg/m²) administered on Day 1 of 2-week cycle. | Cycle 2: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. | Cycle 1: ramucirumab (IMC-1121B) 8 mg/kg administered as monotherapy on Day 1 of 3-week cycle. | Cycle 2 and beyond: ramucirumab (IMC-1121B) 8 mg/kg administered on Day 1 and Day 15, paclitaxel 80 mg/m² administered on Day 1, Day 8 and Day 15 of 4-week cycle. | ||||
All Cause Mortality |
||||||||
| Part A: Paclitaxel Alone (Cycle 1) | Part A: Paclitaxel + Ramucirumab (Cycle 2) | Part B: Ramucirumab Alone (Cycle 1) | Part B: Ramucirumab + Paclitaxel (Cycle 2) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Part A: Paclitaxel Alone (Cycle 1) | Part A: Paclitaxel + Ramucirumab (Cycle 2) | Part B: Ramucirumab Alone (Cycle 1) | Part B: Ramucirumab + Paclitaxel (Cycle 2) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/24 (4.2%) | 6/21 (28.6%) | 0/16 (0%) | 6/15 (40%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/24 (0%) | 0 | 1/21 (4.8%) | 2 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Colitis | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Constipation | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Large intestinal obstruction | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Small intestinal obstruction | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| General disorders | ||||||||
| Non-cardiac chest pain | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Pain | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Pyrexia | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Acute hepatic failure | 1/24 (4.2%) | 1 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Infections and infestations | ||||||||
| Device related infection | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Influenza | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Pneumonia | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Sepsis | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Investigations | ||||||||
| Hepatic enzyme increased | 1/24 (4.2%) | 1 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Hyponatraemia | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Malignant neoplasm progression | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Nervous system disorders | ||||||||
| Depressed level of consciousness | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Hypoaesthesia | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Renal failure acute | 1/24 (4.2%) | 1 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Dyspnoea | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Hypoxia | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 2 |
| Pneumothorax | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pulmonary embolism | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Part A: Paclitaxel Alone (Cycle 1) | Part A: Paclitaxel + Ramucirumab (Cycle 2) | Part B: Ramucirumab Alone (Cycle 1) | Part B: Ramucirumab + Paclitaxel (Cycle 2) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/24 (75%) | 21/21 (100%) | 8/16 (50%) | 14/15 (93.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 3/24 (12.5%) | 4 | 10/21 (47.6%) | 12 | 0/16 (0%) | 0 | 3/15 (20%) | 3 |
| Neutropenia | 1/24 (4.2%) | 1 | 4/21 (19%) | 10 | 0/16 (0%) | 0 | 3/15 (20%) | 7 |
| Thrombocytopenia | 0/24 (0%) | 0 | 2/21 (9.5%) | 3 | 1/16 (6.3%) | 1 | 2/15 (13.3%) | 3 |
| Cardiac disorders | ||||||||
| Tachycardia | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Eye disorders | ||||||||
| Lacrimation increased | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Vision blurred | 1/24 (4.2%) | 1 | 2/21 (9.5%) | 2 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 1 |
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Abdominal pain | 2/24 (8.3%) | 2 | 2/21 (9.5%) | 2 | 1/16 (6.3%) | 1 | 2/15 (13.3%) | 2 |
| Ascites | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 2 | 0/15 (0%) | 0 |
| Breath odour | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Constipation | 4/24 (16.7%) | 4 | 2/21 (9.5%) | 3 | 1/16 (6.3%) | 1 | 3/15 (20%) | 3 |
| Defaecation urgency | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Diarrhoea | 1/24 (4.2%) | 1 | 8/21 (38.1%) | 9 | 1/16 (6.3%) | 1 | 3/15 (20%) | 5 |
| Dry mouth | 1/24 (4.2%) | 1 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 1 |
| Dysphagia | 1/24 (4.2%) | 1 | 1/21 (4.8%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Gastrooesophageal reflux disease | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Nausea | 2/24 (8.3%) | 2 | 5/21 (23.8%) | 9 | 4/16 (25%) | 4 | 4/15 (26.7%) | 4 |
| Rectal haemorrhage | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Stomatitis | 0/24 (0%) | 0 | 4/21 (19%) | 5 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Vomiting | 1/24 (4.2%) | 1 | 4/21 (19%) | 7 | 2/16 (12.5%) | 2 | 2/15 (13.3%) | 2 |
| General disorders | ||||||||
| Application site dermatitis | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Asthenia | 2/24 (8.3%) | 2 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Catheter site inflammation | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Catheter site pain | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Chills | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Face oedema | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Fatigue | 1/24 (4.2%) | 1 | 14/21 (66.7%) | 17 | 2/16 (12.5%) | 2 | 4/15 (26.7%) | 6 |
| Generalised oedema | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Impaired healing | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Malaise | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Non-cardiac chest pain | 1/24 (4.2%) | 1 | 0/21 (0%) | 0 | 1/16 (6.3%) | 2 | 1/15 (6.7%) | 3 |
| Oedema peripheral | 0/24 (0%) | 0 | 5/21 (23.8%) | 7 | 1/16 (6.3%) | 1 | 4/15 (26.7%) | 5 |
| Pyrexia | 1/24 (4.2%) | 1 | 3/21 (14.3%) | 4 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Thrombosis in device | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Infections and infestations | ||||||||
| Bronchitis | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Catheter site cellulitis | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Cellulitis | 0/24 (0%) | 0 | 1/21 (4.8%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Nasopharyngitis | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Rash pustular | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Sinusitis | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Upper respiratory tract infection | 1/24 (4.2%) | 1 | 5/21 (23.8%) | 6 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Urinary tract infection | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 2/15 (13.3%) | 2 |
| Injury, poisoning and procedural complications | ||||||||
| Infusion related reaction | 1/24 (4.2%) | 1 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Skin abrasion | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 1 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Aspartate aminotransferase increased | 0/24 (0%) | 0 | 2/21 (9.5%) | 3 | 0/16 (0%) | 0 | 3/15 (20%) | 3 |
| Blood alkaline phosphatase increased | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Blood bilirubin increased | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Blood creatinine increased | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Lymphocyte count decreased | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 1 |
| Neutrophil count decreased | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 5 |
| Platelet count decreased | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Weight decreased | 0/24 (0%) | 0 | 3/21 (14.3%) | 4 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 1 |
| Weight increased | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| White blood cell count decreased | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 5 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/24 (4.2%) | 1 | 6/21 (28.6%) | 8 | 1/16 (6.3%) | 1 | 3/15 (20%) | 4 |
| Dehydration | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 2 |
| Hyperglycaemia | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 2/15 (13.3%) | 3 |
| Hypoalbuminaemia | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 2/16 (12.5%) | 2 | 3/15 (20%) | 3 |
| Hypocalcaemia | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Hypokalaemia | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Hyponatraemia | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/24 (0%) | 0 | 4/21 (19%) | 5 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Back pain | 1/24 (4.2%) | 1 | 4/21 (19%) | 4 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Bone pain | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Joint range of motion decreased | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Muscle spasms | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Muscular weakness | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Musculoskeletal chest pain | 0/24 (0%) | 0 | 2/21 (9.5%) | 3 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Musculoskeletal discomfort | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Musculoskeletal pain | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 1 |
| Myalgia | 0/24 (0%) | 0 | 4/21 (19%) | 4 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Neck pain | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pain in extremity | 0/24 (0%) | 0 | 3/21 (14.3%) | 3 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 0/24 (0%) | 0 | 3/21 (14.3%) | 3 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Dysgeusia | 0/24 (0%) | 0 | 4/21 (19%) | 4 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Headache | 2/24 (8.3%) | 2 | 7/21 (33.3%) | 8 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Neuralgia | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Neuropathy peripheral | 0/24 (0%) | 0 | 4/21 (19%) | 5 | 0/16 (0%) | 0 | 2/15 (13.3%) | 2 |
| Paraesthesia | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Peripheral sensory neuropathy | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Somnolence | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Psychiatric disorders | ||||||||
| Insomnia | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 1/16 (6.3%) | 1 | 2/15 (13.3%) | 2 |
| Renal and urinary disorders | ||||||||
| Haematuria | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Proteinuria | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 2/16 (12.5%) | 3 | 4/15 (26.7%) | 6 |
| Urinary incontinence | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Reproductive system and breast disorders | ||||||||
| Breast pain | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 2/24 (8.3%) | 2 | 2/21 (9.5%) | 3 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Dysphonia | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Dyspnoea | 1/24 (4.2%) | 1 | 3/21 (14.3%) | 3 | 1/16 (6.3%) | 2 | 1/15 (6.7%) | 1 |
| Epistaxis | 0/24 (0%) | 0 | 7/21 (33.3%) | 7 | 0/16 (0%) | 0 | 6/15 (40%) | 6 |
| Haemoptysis | 0/24 (0%) | 0 | 2/21 (9.5%) | 4 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Oropharyngeal pain | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pleural effusion | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 1/16 (6.3%) | 1 | 0/15 (0%) | 0 |
| Rhinorrhoea | 0/24 (0%) | 0 | 3/21 (14.3%) | 3 | 1/16 (6.3%) | 1 | 1/15 (6.7%) | 1 |
| Sinus congestion | 0/24 (0%) | 0 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Upper-airway cough syndrome | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/24 (0%) | 0 | 6/21 (28.6%) | 6 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Dry skin | 2/24 (8.3%) | 2 | 2/21 (9.5%) | 2 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Nail disorder | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Night sweats | 0/24 (0%) | 0 | 1/21 (4.8%) | 1 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pruritus | 0/24 (0%) | 0 | 3/21 (14.3%) | 3 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Rash | 0/24 (0%) | 0 | 0/21 (0%) | 0 | 0/16 (0%) | 0 | 1/15 (6.7%) | 1 |
| Vascular disorders | ||||||||
| Flushing | 1/24 (4.2%) | 1 | 3/21 (14.3%) | 3 | 0/16 (0%) | 0 | 0/15 (0%) | 0 |
| Hypertension | 0/24 (0%) | 0 | 5/21 (23.8%) | 6 | 1/16 (6.3%) | 1 | 2/15 (13.3%) | 4 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| ClinicalTrials.gov@lilly.com |
- 14432
- I4T-IE-JVCA
- CP12-1032