The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02789345
Recruitment Status : Completed
First Posted : June 3, 2016
Results First Posted : February 5, 2024
Last Update Posted : February 5, 2024
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Drug: Ramucirumab
Drug: Necitumumab
Drug: Osimertinib
Enrollment 29
Recruitment Details

The study consisted of the dose-finding portion (Phase 1a) and the dose-expansion portion (Phase 1b)

  • Phase 1a, Arm A = combination of ramucirumab and osimertinib; Arm B = combination of necitumumab and osimertinib
  • Phase 1b included one cohort, the expansion of Arm A with additional participants enrolled i.e., Cohort A, a combination of ramucirumab and osimertinib. Per Protocol, all outcomes for a combination of ramucirumab and osimertinib were analyzed under a single arm i.e., Arm A/Cohort A
Pre-assignment Details Participants who did not "complete" study were those who discontinued study treatment by the time of study completion.
Arm/Group Title Arm A: Ramucirumab + Osimertinib Arm B: Necitumumab + Osimertinib Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Participants received Necitumumab 800 mg given IV on Days 1 and 8 every 3 weeks and osimertinib 80 mg given orally daily during each 21-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Period Title: Overall Study
Started 3 4 22
Received at Least One Dose of Study Drug 3 4 22
Completed 0 1 5
Not Completed 3 3 17
Reason Not Completed
Adverse Event             0             0             1
Death             0             0             1
Physician Decision             2             0             1
Progressive Disease             1             3             14
Arm/Group Title Arm A: Ramucirumab + Osimertinib Arm B: Necitumumab + Osimertinib Cohort A: Ramucirumab + Osimertinib Total
Hide Arm/Group Description Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Participants received Necitumumab 800 mg given IV on Days 1 and 8 every 3 weeks and osimertinib 80 mg given orally daily during each 21 day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Total of all reporting groups
Overall Number of Baseline Participants 3 4 22 29
Hide Baseline Analysis Population Description
All enrolled participants
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 22 participants 29 participants
<=18 years 0 0 0 0
Between 18 and 65 years 2 2 12 16
>=65 years 1 2 10 13
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 22 participants 29 participants
Female 1 3 17 21
Male 2 1 5 8
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 22 participants 29 participants
Hispanic or Latino 0 0 0 0
Not Hispanic or Latino 3 4 22 29
Unknown or Not Reported 0 0 0 0
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 22 participants 29 participants
American Indian or Alaska Native 0 0 0 0
Asian 0 0 13 13
Native Hawaiian or Other Pacific Islander 0 0 0 0
Black or African American 0 0 0 0
White 3 4 9 16
More than one race 0 0 0 0
Unknown or Not Reported 0 0 0 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 3 participants 4 participants 22 participants 29 participants
South Korea 0 0 6 6
United States 1 1 3 5
Taiwan 0 0 5 5
France 0 1 0 1
Spain 2 2 8 12
1.Primary Outcome
Title Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)
Hide Description

A Dose Limiting Toxicity (DLT) was defined as one of the following Adverse Events (AE) that is likely related to the study drug or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0:

  1. Any nonhematologic Grade ≥3 toxicity, except for toxicities such as liver or renal function abnormality, skin rash that resolves with appropriate therapy, transient hypersensitivity and injection site reactions, myalgia, fatigue, constipation, electrolyte imbalance, nausea, vomiting, diarrhea

  2. Hematologic toxicity was considered a DLT as the following:

    1. Grade 4 toxicity lasting ≥7 days, or
    2. Grade 3 or 4 thrombocytopenia if associated with bleeding or requires platelet transfusion, or
    3. Febrile neutropenia
  3. Death if considered related to study treatment
  4. Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting
Time Frame Arm A: Cycle 1 through Cycle 2 (14-day cycle); Arm B: Cycle 1 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Arm A: participants who either completed the first 2 cycles of treatment or discontinued from study treatment or study participation Arm B: participants who either completed the first cycle of treatment or discontinued from study treatment or study participation
Arm/Group Title Arm A: Ramucirumab + Osimertinib Arm B: Necitumumab + Osimertinib
Hide Arm/Group Description:
Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Participants received Necitumumab 800 mg given IV on Days 1 and 8 every 3 weeks and osimertinib 80 mg given orally daily during each 21 day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
0 0
2.Secondary Outcome
Title Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Hide Description Cmin was the concentration of study drug in the blood immediately before the next dose was administered.
Time Frame Predose on Day (D) 1 of Cycle (C) 2, Predose on Day 1 of Cycle 4, Predose on Day 1 of Cycle 5, Predose on Day 1 of Cycle 7, Predose on Day 1 of Cycle 13
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least one dose of ramucirumab and had evaluable PK data.
Arm/Group Title Arm A/Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description:
Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per milliliter (µg/mL)
D1C2 Number Analyzed 20 participants
41.3
(56.3%)
D1C4 Number Analyzed 16 participants
66.7
(34.3%)
D1C5 Number Analyzed 15 participants
76.7
(27%)
D1C7 Number Analyzed 10 participants
90.7
(26.6%)
D1C13 Number Analyzed 4 participants
103
(29.6%)
3.Secondary Outcome
Title Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab
Hide Description Cmin was the concentration of study drug in the blood immediately before the next dose was administered.
Time Frame Predose on Day 1 of Cycle 3, Predose on Day 1 of Cycle 5
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least one dose of necitumumab and had evaluable PK data.
Arm/Group Title Arm B: Necitumumab + Osimertinib
Hide Arm/Group Description:
Participants received Necitumumab 800 mg given IV on Days 1 and 8 every 3 weeks and osimertinib 80 mg given orally daily during each 21 day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
D1C3 Number Analyzed 2 participants
NA [1] 
(NA%)
D1C5 Number Analyzed 1 participants
NA [2] 
(NA%)
[1]
Geometric Mean and Geometric Coefficient of Variation couldn't be calculated as there were only two participants. Individual values reported: 575476.3 ng/mL and 150490.8 ng/mL
[2]
Geometric Mean and Geometric Coefficient of Variation couldn't be calculated as there was only one participant. Individual value reported: 225257.8 ng/mL
4.Secondary Outcome
Title Objective Response Rate (ORR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With a Complete Response (CR) or Partial Response (PR)
Hide Description ORR was the best overall response of complete response (CR) or partial response (PR) as classified by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). CR was a disappearance of all target and non-target lesions and normalization of tumor marker level. PR was an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time Frame Baseline to Objective Disease Progression (up to 25 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug. Per Protocol, the outcomes for a combination of ramucirumab and osimertinib were analyzed under a single arm (Arm A/Cohort A), as Cohort A is an extension of Arm A.
Arm/Group Title Arm A/Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description:
Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 25
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
76
(58.1 to 89.0)
5.Secondary Outcome
Title Disease Control Rate (DCR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With CR, PR or Stable Disease (SD)
Hide Description DCR was the best overall response of CR, PR, or SD as defined by RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or one or more new lesions.
Time Frame Baseline to Objective Disease Progression (up to 25 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug. Per Protocol, the outcomes for a combination of ramucirumab and osimertinib were analyzed under a single arm (Arm A/Cohort A), as Cohort A is an extension of Arm A.
Arm/Group Title Arm A/Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description:
Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 25
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
92
(76.9 to 98.6)
6.Secondary Outcome
Title Duration of Response (DoR) for Ramucirumab in Combination With Osimertinib
Hide Description Duration of Response (DoR) was defined only for participants with a confirmed CR or PR. It was measured from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever is earlier. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date, DOR was censored at the date of the last complete objective progression-free disease assessment.
Time Frame Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (up to 25 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug with a confirmed CR or PR (including censored). Number of participants censored = 7.
Arm/Group Title Arm A/Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description:
Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 19
Median (90% Confidence Interval)
Unit of Measure: Months
13.37
(9.63 to 21.19)
7.Secondary Outcome
Title Progression Free Survival (PFS) for Ramucirumab in Combination With Osimertinib
Hide Description Progression-free survival (PFS) was the time from the date of first study treatment until the date of radiographic documentation of progression (as defined by RECIST v. 1.1) based on investigator assessment or the date of death due to any cause, whichever was earlier. If a participant did not have a complete baseline disease assessment, then the PFS time was censored at the enrollment date, regardless of whether or not objectively determined disease progression or death was observed for the participant; otherwise, if a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last complete objective progression-free disease assessment date.
Time Frame Baseline to Measured Progressive Disease or Death from Any Cause (up to 26 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug (including censored). Number of participants censored = 7.
Arm/Group Title Arm A/Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description:
Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 25
Median (90% Confidence Interval)
Unit of Measure: Months
11.04
(5.49 to 19.29)
8.Secondary Outcome
Title Overall Survival (OS) for Ramucirumab in Combination With Osimertinib
Hide Description OS was date of first study treatment until death due to any cause. If the participant was alive at the data inclusion cutoff date for the analysis (or was lost to follow-up), OS was censored on the last date the participant was known to be alive.
Time Frame Baseline to Death from Any Cause (up to 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug (including censored). Number of participants censored = 13.
Arm/Group Title Arm A/Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description:
Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
Overall Number of Participants Analyzed 25
Median (90% Confidence Interval)
Unit of Measure: Months
NA [1] 
(16.03 to NA)
[1]
There were not enough events to estimate the median, upper confidence limit.
Time Frame Baseline to follow up (5.38 years)
Adverse Event Reporting Description All enrolled participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
 
Arm/Group Title Arm A: Ramucirumab + Osimertinib Arm B: Necitumumab + Osimertinib Cohort A: Ramucirumab + Osimertinib
Hide Arm/Group Description Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Participants received Necitumumab 800 mg given IV on Days 1 and 8 every 3 weeks and osimertinib 80 mg given orally daily during each 21 day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Participants received Ramucirumab 10 mg/kg given IV on Day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle. All participants were treated until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
All-Cause Mortality
Arm A: Ramucirumab + Osimertinib Arm B: Necitumumab + Osimertinib Cohort A: Ramucirumab + Osimertinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/3 (66.67%)      1/4 (25.00%)      11/22 (50.00%)    
Hide Serious Adverse Events
Arm A: Ramucirumab + Osimertinib Arm B: Necitumumab + Osimertinib Cohort A: Ramucirumab + Osimertinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      1/4 (25.00%)      8/22 (36.36%)    
Blood and lymphatic system disorders       
Thrombocytopenia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  3
Cardiac disorders       
Atrioventricular block second degree † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Cardiac failure congestive † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Gastrointestinal disorders       
Abdominal pain upper † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Intestinal obstruction † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pancreatitis acute † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
General disorders       
Pyrexia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 3/22 (13.64%)  3
Infections and infestations       
Cystitis klebsiella † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Device related infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Diverticulitis † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Pneumonia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Injury, poisoning and procedural complications       
Subdural haemorrhage † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Musculoskeletal and connective tissue disorders       
Osteoarthritis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Renal and urinary disorders       
Acute kidney injury † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Respiratory, thoracic and mediastinal disorders       
Dyspnoea † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pneumothorax † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pulmonary oedema † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
1
Term from vocabulary, MedDRA 22.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm A: Ramucirumab + Osimertinib Arm B: Necitumumab + Osimertinib Cohort A: Ramucirumab + Osimertinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      4/4 (100.00%)      22/22 (100.00%)    
Blood and lymphatic system disorders       
Anaemia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 4/22 (18.18%)  9
Neutropenia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  3
Thrombocytopenia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 3/22 (13.64%)  4
Cardiac disorders       
Angina pectoris † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Cardiac failure congestive † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Palpitations † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Sinus bradycardia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Ear and labyrinth disorders       
Tinnitus † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Vertigo † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Endocrine disorders       
Cushingoid † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Eye disorders       
Blepharospasm † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Cataract † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Diplopia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Eye disorder † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Eyelid oedema † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Glaucoma † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Ocular hyperaemia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Trichiasis † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Trichomegaly † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Visual impairment † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Gastrointestinal disorders       
Abdominal distension † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Abdominal pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Anal fissure † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Anal haemorrhage † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Ascites † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Cheilitis † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Constipation † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 7/22 (31.82%)  7
Diarrhoea † 1  3/3 (100.00%)  3 4/4 (100.00%)  19 14/22 (63.64%)  38
Dyspepsia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/22 (4.55%)  2
Dysphagia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Flatulence † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Gingival bleeding † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 4/22 (18.18%)  6
Haemorrhoids † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Impaired gastric emptying † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Nausea † 1  1/3 (33.33%)  1 2/4 (50.00%)  2 8/22 (36.36%)  11
Odynophagia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Oesophagitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Oral pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pancreatitis acute † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Paraesthesia oral † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Periodontal disease † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Stomatitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 8/22 (36.36%)  16
Transient lingual papillitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Vomiting † 1  1/3 (33.33%)  1 1/4 (25.00%)  1 6/22 (27.27%)  9
General disorders       
Asthenia † 1  1/3 (33.33%)  2 1/4 (25.00%)  11 2/22 (9.09%)  3
Chest pain † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Chills † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Face oedema † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  3
Fatigue † 1  0/3 (0.00%)  0 3/4 (75.00%)  3 3/22 (13.64%)  6
Gait disturbance † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Influenza like illness † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Malaise † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Mucosal dryness † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Mucosal inflammation † 1  0/3 (0.00%)  0 1/4 (25.00%)  2 3/22 (13.64%)  5
Non-cardiac chest pain † 1  1/3 (33.33%)  2 1/4 (25.00%)  2 3/22 (13.64%)  3
Oedema † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 3/22 (13.64%)  3
Oedema peripheral † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 5/22 (22.73%)  10
Pain † 1  0/3 (0.00%)  0 1/4 (25.00%)  2 4/22 (18.18%)  4
Pyrexia † 1  2/3 (66.67%)  3 1/4 (25.00%)  1 3/22 (13.64%)  3
Xerosis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  3
Immune system disorders       
Hypersensitivity † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Infections and infestations       
Conjunctivitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Folliculitis † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Gastroenteritis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Gastrointestinal viral infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Influenza † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/22 (4.55%)  1
Nail infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Nasopharyngitis † 1  1/3 (33.33%)  1 1/4 (25.00%)  1 1/22 (4.55%)  1
Paronychia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 3/22 (13.64%)  10
Periodontitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pneumonia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Rhinitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Sinusitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Skin infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 3/22 (13.64%)  3
Tonsillitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Tooth infection † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Upper respiratory tract infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 5/22 (22.73%)  9
Urinary tract infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 5/22 (22.73%)  7
Viral infection † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Injury, poisoning and procedural complications       
Fall † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Foot fracture † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Humerus fracture † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Infusion related reaction † 1  0/3 (0.00%)  0 1/4 (25.00%)  2 3/22 (13.64%)  3
Skin laceration † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Transfusion reaction † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Wound complication † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Investigations       
Alanine aminotransferase increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Amylase increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  3
Aspartate aminotransferase increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  4
Blood bilirubin increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Blood cholesterol increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Blood creatine phosphokinase increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 4/22 (18.18%)  13
Blood creatinine increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Gamma-glutamyltransferase increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Lipase increased † 1  0/3 (0.00%)  0 1/4 (25.00%)  2 1/22 (4.55%)  4
Neutrophil count decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 3/22 (13.64%)  20
Platelet count decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 6/22 (27.27%)  49
Prothrombin time prolonged † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Transaminases increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  3
Urine output decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Weight decreased † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 3/22 (13.64%)  19
Metabolism and nutrition disorders       
Decreased appetite † 1  1/3 (33.33%)  2 2/4 (50.00%)  3 9/22 (40.91%)  11
Hyperglycaemia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Hyperkalaemia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Hypoalbuminaemia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  6
Hypomagnesaemia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Hyponatraemia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 2/22 (9.09%)  2
Hypophosphataemia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  2/3 (66.67%)  2 1/4 (25.00%)  1 4/22 (18.18%)  5
Back pain † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 5/22 (22.73%)  7
Muscle spasms † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Muscular weakness † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Musculoskeletal chest pain † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/22 (4.55%)  1
Musculoskeletal pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Myalgia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Osteoarthritis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Pain in extremity † 1  1/3 (33.33%)  1 1/4 (25.00%)  1 3/22 (13.64%)  6
Spinal osteoarthritis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Haemangioma † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pyogenic granuloma † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Nervous system disorders       
Cerebral haemorrhage † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Dizziness † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 4/22 (18.18%)  4
Dysarthria † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Facial paralysis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Headache † 1  1/3 (33.33%)  1 1/4 (25.00%)  1 9/22 (40.91%)  11
Memory impairment † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Neurological decompensation † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Neuropathy peripheral † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Paraesthesia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Peripheral sensory neuropathy † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Presyncope † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Tremor † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Psychiatric disorders       
Anxiety † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 2/22 (9.09%)  2
Confusional state † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Insomnia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 2/22 (9.09%)  2
Mental status changes † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Renal and urinary disorders       
Cystitis noninfective † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Dysuria † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Haematuria † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Micturition disorder † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Nocturia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pollakiuria † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Proteinuria † 1  1/3 (33.33%)  2 0/4 (0.00%)  0 4/22 (18.18%)  8
Renal impairment † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/22 (0.00%)  0
Reproductive system and breast disorders       
Pruritus genital † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Vulvovaginal dryness † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/17 (5.88%)  1
Respiratory, thoracic and mediastinal disorders       
Asthma † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Cough † 1  3/3 (100.00%)  3 0/4 (0.00%)  0 6/22 (27.27%)  8
Dry throat † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Dyspnoea † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 4/22 (18.18%)  7
Dyspnoea exertional † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/22 (4.55%)  1
Epistaxis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 4/22 (18.18%)  7
Nasal congestion † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 2/22 (9.09%)  2
Nasal dryness † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Oropharyngeal pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Pleural effusion † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 4/22 (18.18%)  24
Pleuritic pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Pneumothorax † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Productive cough † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 3/22 (13.64%)  6
Pulmonary haemorrhage † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Rhinitis allergic † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Rhinorrhoea † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
Sputum discoloured † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Upper-airway cough syndrome † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Skin and subcutaneous tissue disorders       
Alopecia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Cold sweat † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Dermal cyst † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Dermatitis acneiform † 1  1/3 (33.33%)  1 2/4 (50.00%)  12 0/22 (0.00%)  0
Dermatitis allergic † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Dry skin † 1  1/3 (33.33%)  1 3/4 (75.00%)  4 2/22 (9.09%)  3
Hirsutism † 1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/22 (0.00%)  0
Nail dystrophy † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Onychoclasis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Onycholysis † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/22 (4.55%)  1
Onychomadesis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Petechiae † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 3/22 (13.64%)  6
Pruritus † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 5/22 (22.73%)  9
Purpura † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Rash † 1  1/3 (33.33%)  1 2/4 (50.00%)  9 4/22 (18.18%)  7
Rash maculo-papular † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Skin exfoliation † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  2
Skin fissures † 1  0/3 (0.00%)  0 1/4 (25.00%)  3 2/22 (9.09%)  2
Skin irritation † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/22 (0.00%)  0
Skin lesion † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Vascular disorders       
Deep vein thrombosis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/22 (4.55%)  1
Hypertension † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 14/22 (63.64%)  24
Hypotension † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/22 (9.09%)  2
1
Term from vocabulary, MedDRA 22.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
EMail: ClinicalTrials.gov@lilly.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02789345    
Other Study ID Numbers: 16357
I4T-MC-JVDL ( Other Identifier: Eli Lilly and Company )
2015-005296-25 ( EudraCT Number )
First Submitted: May 31, 2016
First Posted: June 3, 2016
Results First Submitted: May 23, 2023
Results First Posted: February 5, 2024
Last Update Posted: February 5, 2024