A Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01606748
Collaborator
(none)
35
4
1
46
8.8
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to investigate the pharmacokinetics (PK) of necitumumab in combination with gemcitabine-cisplatin in participants with advanced malignant solid tumors and to assess the potential for drug-drug interactions between necitumumab and gemcitabine-cisplatin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
35 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Non-controlled, Non-randomized Sequential Design, Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin in Patients With Advanced Solid Cancers
Study Start Date
:
Aug 1, 2012
Actual Primary Completion Date
:
Jun 1, 2013
Actual Study Completion Date
:
Jun 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Necitumumab, Gemcitabine and Cisplatin The study will be conducted in two sequential periods: a 3-week PK run-in participants will be treated sequentially with single doses of cisplatin, gemcitabine, and necitumumab. Cycle 1 will begin immediately following the PK run-in period. |
Biological: Necitumumab
PK Run-In Period: Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (I.V.) infusion at an absolute dose of 800 mg
Treatment Cycles: Necitumumab administered on Days 1 and 8 of every 3-week cycle as an intravenous (I.V.) infusion at an absolute dose of 800 mg
Participants in Cohort 1 will receive necitumumab Process C drug product and participants in Cohort 2 will receive necitumumab Process D drug product
Other Names:
Drug: Gemcitabine
PK Run-In Period: Gemcitabine administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 1250 milligram per square meter (mg/m2)
Treatment Cycles: Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an I.V. infusion at a dose of 1250 mg/m2
Other Names:
Drug: Cisplatin
PK Run-In Period: Cisplatin administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 75 mg/m2
Treatment Cycles: Cisplatin administered on Day 1 of every 3-week cycle as an I.V. infusion at a dose of 75 mg/m2
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab [Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion]
- PK: Dose-Normalized Cmax of Gemcitabine [Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion]
- PK: Dose-Normalized Cmax of Cisplatin [Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion]
- PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab [Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion]
- PK: Dose-Normalized AUC(0-24) of Gemcitabine [Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion]
- PK: Dose-Normalized AUC(0-5) of Cisplatin [Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion]
- PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab [Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion]
- PK: Dose Normalized AUC(0-∞) of Gemcitabine [Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion]
Secondary Outcome Measures
- Number of Participants With Anti-Necitumumab Antibodies [Baseline through, 30-Day Follow-Up]
A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy) [Baseline to Measured Progressive Disease (Up to 14 Months)]
ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100.
- PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product [Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion]
- PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product [Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have documented advanced or metastatic malignant solid tumors (except for colorectal tumors with KRAS mutation) that are resistant to standard therapy or for which no standard therapy is available
-
May have measurable or non-measurable disease
-
Have resolution to Grade 0 or 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE 4.0) of all clinically significant toxic effects (other than alopecia) of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
-
Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
-
Have adequate hepatic, hematologic and renal function
-
If female, are surgically sterile, postmenopausal, or agree to be compliant with a highly effective contraceptive method during and for 6 months after the treatment period. If male, are surgically sterile or agree to be compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
-
Female participants of childbearing potential have a negative serum pregnancy test within 7 days prior to the first dose of study therapy
Exclusion Criteria:
-
Have received a systemic anticancer agent (including EGFR tyrosine kinase inhibitors) or device within 28 days prior to first dose of study therapy
-
The most recent anticancer therapy received by the participant included either gemcitabine or cisplatin (or both)
-
Have received radiotherapy within 14 days prior to first dose of study therapy
-
Have received cytotoxic chemotherapy within 21 days prior to first dose of study therapy
-
Are receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, or targeted therapy
-
Are considered surgical candidates (with resectable disease)
-
Have brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants
-
Have narrowing of or blockage in large veins
-
Have coronary artery disease or uncontrolled congestive heart failure
-
Have uncontrolled angina pectoris, or experienced myocardial infarction within 6 months prior to first dose of study therapy
-
Have an ongoing or active infection (requiring treatment), including active tuberculosis or known infection with the human immunodeficiency virus
-
Have a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
-
Have known drug or alcohol abuse
-
If female, are pregnant or breastfeeding
-
Have 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 therapy
-
Are currently enrolled in, or discontinued within the 30 days prior to first dose of study therapy from a clinical trial involving an investigational product or nonapproved 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Scottsdale | Arizona | United States | 85258 |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Detroit | Michigan | United States | 48202 |
| 3 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Las Vegas | Nevada | United States | 89169 |
| 4 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Pittsburgh | Pennsylvania | United States | 15213 |
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.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01606748
Other Study ID Numbers:
- 14473
- CP11-1115
- I4X-IE-JFCJ
First Posted:
May 28, 2012
Last Update Posted:
Sep 30, 2019
Last Verified:
Sep 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Cohort 1 'completers' completed the PK run-in period (3 Weeks) and Cycle 1, Day 1 and Cohort 2 'completers' completed the PK run-in period. |
| Arm/Group Title | Necitumumab Cohort 1 | Necitumumab Cohort 2 |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (IV) infusion at an absolute dose of 800 milligrams (mg). Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/square meter (m2). Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 2 received necitumumab drug product manufactured using a new and comparable necitumumab drug substance (Process D drug product). Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Period Title: Overall Study | ||
| STARTED | 18 | 17 |
| Received at Least 1 Dose of Study Drug | 18 | 17 |
| COMPLETED | 15 | 17 |
| NOT COMPLETED | 3 | 0 |
Baseline Characteristics
| Arm/Group Title | Necitumumab Cohort 1 | Necitumumab Cohort 2 | Total |
|---|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Total of all reporting groups |
| Overall Participants | 18 | 17 | 35 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
55.3
(15.54)
|
58.2
(13.84)
|
56.7
(14.59)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
11
61.1%
|
10
58.8%
|
21
60%
|
| Male |
7
38.9%
|
7
41.2%
|
14
40%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
5.6%
|
1
5.9%
|
2
5.7%
|
| Not Hispanic or Latino |
17
94.4%
|
16
94.1%
|
33
94.3%
|
| 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
5.6%
|
0
0%
|
1
2.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
3
17.6%
|
3
8.6%
|
| White |
17
94.4%
|
14
82.4%
|
31
88.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
18
100%
|
17
100%
|
35
100%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline (participants) [Number] | |||
| 0 |
9
50%
|
7
41.2%
|
16
45.7%
|
| 1 |
9
50%
|
10
58.8%
|
19
54.3%
|
| >=2 |
0
0%
|
0
0%
|
0
0%
|
| Disease Characteristics - Tumor Type (participants) [Number] | |||
| Breast Carcinoma |
3
16.7%
|
4
23.5%
|
7
20%
|
| Ovarian Carcinoma |
2
11.1%
|
1
5.9%
|
3
8.6%
|
| Small Cell Lung Carcinoma |
2
11.1%
|
1
5.9%
|
3
8.6%
|
| Thymic Tumor |
2
11.1%
|
0
0%
|
2
5.7%
|
| Nonsmall Cell Lung Carcinoma |
2
11.1%
|
0
0%
|
2
5.7%
|
| Melanoma |
1
5.6%
|
1
5.9%
|
2
5.7%
|
| Head and Neck Carcinoma |
1
5.6%
|
1
5.9%
|
2
5.7%
|
| Endometrial Carcinoma |
1
5.6%
|
1
5.9%
|
2
5.7%
|
| Hepatobilliary Carcinoma |
1
5.6%
|
0
0%
|
1
2.9%
|
| Left Parotid |
1
5.6%
|
0
0%
|
1
2.9%
|
| Liver |
1
5.6%
|
0
0%
|
1
2.9%
|
| Granulosa Cell Tumor of the Ovary |
1
5.6%
|
0
0%
|
1
2.9%
|
| Mesothelioma |
0
0%
|
1
5.9%
|
1
2.9%
|
| Neuroendocrine Tumor |
0
0%
|
1
5.9%
|
1
2.9%
|
| Hepatocellular Carcinoma |
0
0%
|
1
5.9%
|
1
2.9%
|
| Esophageal Carcinoma |
0
0%
|
1
5.9%
|
1
2.9%
|
| Colorectal Carcinoma |
0
0%
|
1
5.9%
|
1
2.9%
|
| Sarcoma, soft tissue |
0
0%
|
1
5.9%
|
1
2.9%
|
| Adenocarcinoma of the Ampula of Vater |
0
0%
|
1
5.9%
|
1
2.9%
|
| Pancreatic Carcinoma |
0
0%
|
1
5.9%
|
1
2.9%
|
| Prior Anti-Cancer Therapy (participants) [Number] | |||
| Any Prior Radiotherapy |
13
72.2%
|
10
58.8%
|
23
65.7%
|
| Any Prior (Adjuvant/Neoadjuvant) Systemic Therapy |
17
94.4%
|
16
94.1%
|
33
94.3%
|
Outcome Measures
| Title | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. |
| Arm/Group Title | Necitumumab Cohort 1 Day 3 Run-in | Necitumumab Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product. | Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product. |
| Measure Participants | 18 | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [microgram/milliliter (ug/mL)] |
277
(22)
|
315
(23)
|
| Title | PK: Dose-Normalized Cmax of Gemcitabine |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2. |
| Arm/Group Title | Gemcitabine Cohort 1 Day 1 PK Run-In | Gemcitabine Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. | Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Measure Participants | 18 | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram(ng)/mL/mg] |
4.83
(66)
|
7.87
(43)
|
| Title | PK: Dose-Normalized Cmax of Cisplatin |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2. |
| Arm/Group Title | Cisplatin Cohort 1 Day 1 Run-in | Cisplatin Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Cisplatin administered on Day 1 of the 3-week PK run-in period as an IV infusion of 75 mg/m2. | Cisplatin administered 75 mg/m2 on Days 1 and 8 of every 3-week cycle as an IV infusion. |
| Measure Participants | 18 | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram (ng)/mL/mg] |
19.2
(21)
|
22.1
(30)
|
| Title | PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2. |
| Arm/Group Title | Necitumumab Cohort 1 Day 3 Run-In | Necitumumab Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. | Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. |
| Measure Participants | 18 | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [ug*hour(h)/mL] |
21900
(24)
|
22900
(34)
|
| Title | Number of Participants With Anti-Necitumumab Antibodies |
|---|---|
| Description | A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer. |
| Time Frame | Baseline through, 30-Day Follow-Up |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable baseline and postbaseline data for antibodies. |
| Arm/Group Title | Necitumumab Cohort 1 | Necitumumab Cohort 2 |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Measure Participants | 18 | 17 |
| ADA Positive |
3
16.7%
|
0
0%
|
| TE Antibodies |
1
5.6%
|
0
0%
|
| Neutralizing Antibodies |
0
0%
|
0
0%
|
| Title | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy) |
|---|---|
| Description | ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100. |
| Time Frame | Baseline to Measured Progressive Disease (Up to 14 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | Necitumumab Cohort 1 | Necitumumab Cohort 2 |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Measure Participants | 18 | 17 |
| Number (95% Confidence Interval) [percentage of participants] |
16.7
92.8%
|
5.9
34.7%
|
| Title | PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. |
| Arm/Group Title | Necitumumab Cohort 1 | Necitumumab Cohort 2 |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Measure Participants | 18 | 17 |
| Geometric Mean (Geometric Coefficient of Variation) [ug/mL] |
277
(22)
|
300
(36)
|
| Title | PK: Dose-Normalized AUC(0-24) of Gemcitabine |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2. |
| Arm/Group Title | Gemcitabine Cohort 1 Day 1 PK Run-in | Gemcitabine Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. | Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Measure Participants | 17 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL/mg] |
2.71
(45)
|
3.31
(33)
|
| Title | PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. |
| Arm/Group Title | Necitumumab Cohort 1 | Necitumumab Cohort 2 |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Measure Participants | 14 | 14 |
| Geometric Mean (Geometric Coefficient of Variation) [ug*h/mL] |
33800
(33)
|
35500
(35)
|
| Title | PK: Dose-Normalized AUC(0-5) of Cisplatin |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2. |
| Arm/Group Title | Cisplatin Cohort 1 Day 1 Run-in | Cisplatin Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Cisplatin administered on Day 1 of the 3-week PK run-in period as an IV infusion of 75 mg/m2. | Cisplatin administered 75 mg/m2 on Days 1 and 8 of every 3-week cycle as an IV infusion. |
| Measure Participants | 17 | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL/mg] |
61.5
(20)
|
67.3
(24)
|
| Title | PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. |
| Arm/Group Title | Necitumumab Cohort 1 Day 3 PK Run-In | Necitumumab Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. | Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. |
| Measure Participants | 14 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [ug*h/mL] |
33800
(33)
|
26400
(30)
|
| Title | PK: Dose Normalized AUC(0-∞) of Gemcitabine |
|---|---|
| Description | |
| Time Frame | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2. |
| Arm/Group Title | Gemcitabine Cohort 1 Day 1 PK Run-in | Gemcitabine Cohort 1 Day 1, Cycle 1, Combination |
|---|---|---|
| Arm/Group Description | Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. | Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. |
| Measure Participants | 17 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL/mg] |
2.72
(45)
|
3.32
(33)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one dose of study drug. | |||
| Arm/Group Title | Necitumumab Cohort 1 | Necitumumab Cohort 2 | ||
| Arm/Group Description | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | ||
All Cause Mortality |
||||
| Necitumumab Cohort 1 | Necitumumab Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Necitumumab Cohort 1 | Necitumumab Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/18 (27.8%) | 8/17 (47.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Febrile neutropenia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Pancytopenia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Thrombocytopenia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Eye disorders | ||||
| Eye pain | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Intestinal obstruction | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Nausea | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Small intestinal obstruction | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| General disorders | ||||
| Asthenia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Pyrexia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Infections and infestations | ||||
| Catheter site infection | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Implant site cellulitis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Sepsis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Skin infection | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Staphylococcal infection | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Urinary tract infection bacterial | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Fall | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Dehydration | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Hypokalaemia | 0/18 (0%) | 0 | 1/17 (5.9%) | 3 |
| Hypomagnesaemia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nervous system disorders | ||||
| Cerebral ischaemia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Ischaemic stroke | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Presyncope | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Renal and urinary disorders | ||||
| Renal failure acute | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Epistaxis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypoxia | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Pulmonary embolism | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Vascular disorders | ||||
| Hypertension | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Necitumumab Cohort 1 | Necitumumab Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/18 (100%) | 17/17 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 10/18 (55.6%) | 51 | 13/17 (76.5%) | 50 |
| Anisocytosis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Leukocytosis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Leukopenia | 2/18 (11.1%) | 8 | 5/17 (29.4%) | 14 |
| Lymphopenia | 2/18 (11.1%) | 2 | 4/17 (23.5%) | 10 |
| Macrocytosis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Microcytosis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Neutropenia | 8/18 (44.4%) | 25 | 9/17 (52.9%) | 18 |
| Thrombocytopenia | 11/18 (61.1%) | 25 | 6/17 (35.3%) | 26 |
| Cardiac disorders | ||||
| Palpitations | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Tachycardia | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Ear and labyrinth disorders | ||||
| Cerumen impaction | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Deafness | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Ear pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Tinnitus | 5/18 (27.8%) | 6 | 1/17 (5.9%) | 1 |
| Eye disorders | ||||
| Asthenopia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Dry eye | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Eye irritation | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Eye pain | 2/18 (11.1%) | 2 | 0/17 (0%) | 0 |
| Growth of eyelashes | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Lacrimation increased | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Periorbital oedema | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Photophobia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Photopsia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Trichiasis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Vision blurred | 2/18 (11.1%) | 2 | 3/17 (17.6%) | 3 |
| Visual acuity reduced | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Visual impairment | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Abdominal distension | 0/18 (0%) | 0 | 5/17 (29.4%) | 5 |
| Abdominal pain | 1/18 (5.6%) | 1 | 3/17 (17.6%) | 5 |
| Abdominal pain upper | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Ascites | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Cheilitis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Constipation | 7/18 (38.9%) | 7 | 6/17 (35.3%) | 13 |
| Diarrhoea | 6/18 (33.3%) | 9 | 7/17 (41.2%) | 11 |
| Dry mouth | 0/18 (0%) | 0 | 4/17 (23.5%) | 4 |
| Duodenal ulcer | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Dyspepsia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Dysphagia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Gastrooesophageal reflux disease | 2/18 (11.1%) | 2 | 2/17 (11.8%) | 2 |
| Gingival bleeding | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Glossodynia | 2/18 (11.1%) | 2 | 0/17 (0%) | 0 |
| Haematochezia | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Haemorrhoids | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Lip disorder | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nausea | 12/18 (66.7%) | 15 | 10/17 (58.8%) | 26 |
| Oral pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Sensitivity of teeth | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Stomatitis | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Stomatitis necrotising | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Vomiting | 10/18 (55.6%) | 13 | 6/17 (35.3%) | 16 |
| General disorders | ||||
| Asthenia | 1/18 (5.6%) | 2 | 1/17 (5.9%) | 1 |
| Catheter site haemorrhage | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Catheter site pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Chills | 1/18 (5.6%) | 1 | 3/17 (17.6%) | 4 |
| Device deployment issue | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Device leakage | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Fatigue | 14/18 (77.8%) | 19 | 13/17 (76.5%) | 28 |
| Gait disturbance | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Implant site erythema | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Implant site irritation | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Mucosal dryness | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Mucosal inflammation | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Non-cardiac chest pain | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Oedema | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Oedema peripheral | 0/18 (0%) | 0 | 2/17 (11.8%) | 5 |
| Pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Pyrexia | 1/18 (5.6%) | 1 | 3/17 (17.6%) | 4 |
| Tenderness | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Immune system disorders | ||||
| Multiple allergies | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Infections and infestations | ||||
| Abscess neck | 1/18 (5.6%) | 2 | 0/17 (0%) | 0 |
| Abscess oral | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Bronchitis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Cellulitis orbital | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Fungal skin infection | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hand-foot-and-mouth disease | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Herpes zoster | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Oral herpes | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Paronychia | 1/18 (5.6%) | 4 | 0/17 (0%) | 0 |
| Rash pustular | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Sinusitis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Upper respiratory tract infection | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Urinary tract infection | 1/18 (5.6%) | 1 | 3/17 (17.6%) | 6 |
| Injury, poisoning and procedural complications | ||||
| Excoriation | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Fall | 0/18 (0%) | 0 | 1/17 (5.9%) | 3 |
| Gastrostomy failure | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Infusion related reaction | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 2 |
| Laceration | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Procedural pain | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Wound | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 1/18 (5.6%) | 1 | 6/17 (35.3%) | 7 |
| Alanine aminotransferase decreased | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Alanine aminotransferase increased | 8/18 (44.4%) | 15 | 5/17 (29.4%) | 7 |
| Aspartate aminotransferase increased | 11/18 (61.1%) | 16 | 8/17 (47.1%) | 12 |
| Blood albumin decreased | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Blood alkaline phosphatase increased | 4/18 (22.2%) | 9 | 2/17 (11.8%) | 5 |
| Blood bilirubin increased | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Blood cholesterol increased | 1/18 (5.6%) | 1 | 3/17 (17.6%) | 3 |
| Blood creatine phosphokinase increased | 4/18 (22.2%) | 4 | 1/17 (5.9%) | 1 |
| Blood creatinine increased | 4/18 (22.2%) | 11 | 5/17 (29.4%) | 15 |
| Blood fibrinogen increased | 2/18 (11.1%) | 2 | 2/17 (11.8%) | 2 |
| Blood magnesium decreased | 3/18 (16.7%) | 3 | 0/17 (0%) | 0 |
| Blood magnesium increased | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Blood potassium decreased | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Blood urea increased | 4/18 (22.2%) | 9 | 3/17 (17.6%) | 3 |
| Blood uric acid increased | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Blood urine present | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Carbohydrate antigen 125 increased | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Carbohydrate antigen 19-9 increased | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Carcinoembryonic antigen increased | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Fibrin d dimer increased | 5/18 (27.8%) | 6 | 2/17 (11.8%) | 3 |
| Glucose urine present | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Haematocrit decreased | 3/18 (16.7%) | 4 | 0/17 (0%) | 0 |
| Haemoglobin decreased | 3/18 (16.7%) | 5 | 0/17 (0%) | 0 |
| International normalised ratio increased | 3/18 (16.7%) | 3 | 1/17 (5.9%) | 1 |
| Lymphocyte count decreased | 7/18 (38.9%) | 13 | 5/17 (29.4%) | 22 |
| Lymphocyte count increased | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Monocyte count decreased | 3/18 (16.7%) | 3 | 0/17 (0%) | 0 |
| Monocyte count increased | 4/18 (22.2%) | 5 | 0/17 (0%) | 0 |
| Neutrophil count decreased | 7/18 (38.9%) | 24 | 4/17 (23.5%) | 12 |
| Neutrophil count increased | 5/18 (27.8%) | 5 | 0/17 (0%) | 0 |
| Platelet count decreased | 8/18 (44.4%) | 13 | 5/17 (29.4%) | 15 |
| Platelet count increased | 3/18 (16.7%) | 3 | 0/17 (0%) | 0 |
| Protein urine present | 1/18 (5.6%) | 1 | 2/17 (11.8%) | 2 |
| Prothrombin time prolonged | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Red blood cell count decreased | 2/18 (11.1%) | 4 | 0/17 (0%) | 0 |
| Urine leukocyte esterase | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Weight decreased | 0/18 (0%) | 0 | 4/17 (23.5%) | 4 |
| Weight increased | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| White blood cell count decreased | 10/18 (55.6%) | 23 | 7/17 (41.2%) | 15 |
| White blood cell count increased | 2/18 (11.1%) | 2 | 0/17 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 7/18 (38.9%) | 7 | 7/17 (41.2%) | 14 |
| Dehydration | 1/18 (5.6%) | 1 | 3/17 (17.6%) | 4 |
| Hypercalcaemia | 0/18 (0%) | 0 | 4/17 (23.5%) | 7 |
| Hypercholesterolaemia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hyperglycaemia | 2/18 (11.1%) | 4 | 1/17 (5.9%) | 1 |
| Hypermagnesaemia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Hypernatraemia | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Hyperuricaemia | 0/18 (0%) | 0 | 1/17 (5.9%) | 3 |
| Hypoalbuminaemia | 4/18 (22.2%) | 12 | 9/17 (52.9%) | 12 |
| Hypocalcaemia | 3/18 (16.7%) | 6 | 5/17 (29.4%) | 8 |
| Hypoglycaemia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypokalaemia | 8/18 (44.4%) | 20 | 7/17 (41.2%) | 20 |
| Hypomagnesaemia | 10/18 (55.6%) | 30 | 12/17 (70.6%) | 32 |
| Hyponatraemia | 4/18 (22.2%) | 7 | 4/17 (23.5%) | 6 |
| Hypophosphataemia | 2/18 (11.1%) | 2 | 1/17 (5.9%) | 1 |
| Malnutrition | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Metabolic acidosis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Vitamin d deficiency | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/18 (5.6%) | 1 | 3/17 (17.6%) | 3 |
| Bone pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Flank pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Joint range of motion decreased | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Muscle spasms | 2/18 (11.1%) | 2 | 0/17 (0%) | 0 |
| Muscular weakness | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Musculoskeletal chest pain | 1/18 (5.6%) | 2 | 0/17 (0%) | 0 |
| Musculoskeletal stiffness | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Myalgia | 0/18 (0%) | 0 | 3/17 (17.6%) | 5 |
| Neck pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Pain in extremity | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Benign neoplasm | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nervous system disorders | ||||
| Cognitive disorder | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Dizziness | 1/18 (5.6%) | 1 | 4/17 (23.5%) | 5 |
| Dysgeusia | 2/18 (11.1%) | 2 | 7/17 (41.2%) | 10 |
| Headache | 4/18 (22.2%) | 6 | 5/17 (29.4%) | 7 |
| Memory impairment | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Neuropathy peripheral | 3/18 (16.7%) | 3 | 2/17 (11.8%) | 2 |
| Paraesthesia | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Presyncope | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Sinus headache | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Tremor | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Psychiatric disorders | ||||
| Anxiety | 2/18 (11.1%) | 2 | 3/17 (17.6%) | 3 |
| Depression | 3/18 (16.7%) | 4 | 2/17 (11.8%) | 2 |
| Insomnia | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Mental status changes | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Restlessness | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Renal and urinary disorders | ||||
| Dysuria | 0/18 (0%) | 0 | 2/17 (11.8%) | 2 |
| Haematuria | 1/18 (5.6%) | 1 | 2/17 (11.8%) | 2 |
| Micturition urgency | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nocturia | 2/18 (11.1%) | 2 | 0/17 (0%) | 0 |
| Pollakiuria | 0/18 (0%) | 0 | 3/17 (17.6%) | 3 |
| Proteinuria | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Renal failure | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Urinary incontinence | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Urinary tract pain | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Atelectasis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Cough | 4/18 (22.2%) | 4 | 4/17 (23.5%) | 4 |
| Dyspnoea | 5/18 (27.8%) | 5 | 3/17 (17.6%) | 4 |
| Dyspnoea exertional | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Epistaxis | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Hiccups | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Hypoxia | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nasal congestion | 0/18 (0%) | 0 | 4/17 (23.5%) | 7 |
| Nasal dryness | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Oropharyngeal pain | 0/18 (0%) | 0 | 3/17 (17.6%) | 3 |
| Pleural effusion | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Productive cough | 1/18 (5.6%) | 2 | 1/17 (5.9%) | 2 |
| Rhinorrhoea | 1/18 (5.6%) | 1 | 4/17 (23.5%) | 4 |
| Sinus congestion | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Upper-airway cough syndrome | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Wheezing | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 1/18 (5.6%) | 1 | 2/17 (11.8%) | 2 |
| Dermatitis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Dermatitis acneiform | 4/18 (22.2%) | 5 | 8/17 (47.1%) | 8 |
| Dry skin | 3/18 (16.7%) | 3 | 3/17 (17.6%) | 3 |
| Erythema | 1/18 (5.6%) | 1 | 2/17 (11.8%) | 2 |
| Hirsutism | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Hyperhidrosis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Ingrowing nail | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Night sweats | 1/18 (5.6%) | 1 | 1/17 (5.9%) | 1 |
| Onychomadesis | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 5/18 (27.8%) | 5 | 2/17 (11.8%) | 2 |
| Pruritus | 1/18 (5.6%) | 3 | 2/17 (11.8%) | 3 |
| Rash | 5/18 (27.8%) | 7 | 5/17 (29.4%) | 8 |
| Rash macular | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Rash maculo-papular | 7/18 (38.9%) | 10 | 0/17 (0%) | 0 |
| Rash papular | 0/18 (0%) | 0 | 1/17 (5.9%) | 2 |
| Rash pruritic | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Skin fissures | 0/18 (0%) | 0 | 2/17 (11.8%) | 3 |
| Skin hyperpigmentation | 0/18 (0%) | 0 | 2/17 (11.8%) | 4 |
| Skin irritation | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Skin lesion | 2/18 (11.1%) | 2 | 0/17 (0%) | 0 |
| Skin reaction | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Swelling face | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Vascular disorders | ||||
| Deep vein thrombosis | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Flushing | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hot flush | 1/18 (5.6%) | 1 | 0/17 (0%) | 0 |
| Hypertension | 2/18 (11.1%) | 2 | 1/17 (5.9%) | 1 |
| Hypotension | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
| Orthostatic hypotension | 0/18 (0%) | 0 | 1/17 (5.9%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01606748
Other Study ID Numbers:
- 14473
- CP11-1115
- I4X-IE-JFCJ
First Posted:
May 28, 2012
Last Update Posted:
Sep 30, 2019
Last Verified:
Sep 1, 2019