A Study of LY3023414 and Necitumumab in Squamous Lung Cancer
Study Details
Study Description
Brief Summary
The main purpose of this study is to evaluate the safety and activity of the study drug known as LY3023414 in combination with necitumumab in participants with metastatic squamous non-small cell lung cancer (NSCLC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY3023414 + Necitumumab 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. |
Drug: LY3023414
Administered orally
Drug: Necitumumab
Administered IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at 6 Months: Disease Control Rate (DCR) [6 Months]
RECIST v 1.1 was used to assess tumor response.The 6-month DCR was defined as the number of participants with PFS > 6 months (or 26 weeks, to accommodate the scheduled tumor assessment at week 24 be delayed by up to 2 weeks) divided by number of participants with baseline tumor assessment. Target Lesions:CR was defined as the disappearance of all target lesions. PR was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest (nadir) sum of diameters since the treatment started. Non-Target Lesions:CR was defined as disappearance of all non-target lesions and normalization of tumor markers.All lymph nodes must be non-pathological in size (<10 millimeters(mm) short axis).SD was defined as the persistence of one or more non-target lesions and/or persistence of tumor marker level above the normal limits.
Secondary Outcome Measures
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [Baseline to Objective Disease Progression or Initiation of Subsequent Anticancer Therapy (Up To 3 Months)]
RECIST v 1.1 was used to assess tumor response. ORR for a given participant was based on objective responses determined from data obtained up to: progression, the last evaluable assessment in the absence of progression, or initiation of subsequent anticancer therapy. Participants for whom an objective response cannot be determined or for who the best objective response is not evaluable (NE) were considered non-responders. Target Lesions: CR was defined as the disappearance of all target lesions. PR was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesions: CR was defined as disappearance of all non-target lesions and normalization of tumor markers. All lymph nodes must be non-pathological in size (<10 mm short axis). The ORR percentage was calculated as the number of participants with best objective response of CR or PR divided by the number of participants with measurable disease at baseline.
- Progression Free Survival (PFS) [Enrollment to Measured Progressive Disease or Death from Any Cause (Up To 12 Months)]
PFS was defined as the time from enrollment until the date of disease progression per RECIST v 1.1 or death by any cause.Participants who had not progressed or died at the time of assessment were censored at the time of the last date of tumor assessment.Participants who are enrolled but do not receive treatment and participants who have no evaluable visits will be censored on day 1.Participants who received new anti-cancer therapy before disease progression or death will be censored to the last tumor assessment date prior to the new anti-cancer therapy. Target Lesions:PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest(nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over sum. Non-Target Lesions(NTL):PD is defined as appearance of one or more new lesions and/or unequivocal progression of existing NTL.
- Overall Survival (OS) [Enrollment to Death from Any Cause (Up To 16 Months)]
OS was defined as the time from enrollment until the date of death by any cause. Participants lost follow up or did not die at the time of assessment were censored at the time of the last known alive date.
- Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3023414 and Necitumumab [Cycle 1 Day 8, and Cycle 3 Day 8 (pre-dose, end of necitumumab infusion and 1 hour post-necitumumab infusion), Cycle 2 Day 1, Cycle 4 Day 1]
Minimum Concentration (Cmin) of LY3023414 and Necitumumab
- Pharmacokinetics: Maximum Concentration (Cmax) of LY3023414 and Necitumumab [Cycle 1 Day 8, and Cycle 3 Day 8 (pre-dose, end of necitumumab infusion and 1 hour post-necitumumab infusion)]
Maximum Concentration (Cmax) of LY3023414 and Necitumumab
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed squamous advanced NSCLC (Stage IV).
-
Participants must have progressed on one prior line of platinum-based chemotherapy in the advanced or metastatic setting.
-
Measurable disease as measured by response evaluation criteria in solid tumors (RECIST) criteria v 1.1.
-
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
-
Able to swallow the study drugs whole.
-
Adequate organ function.
-
Women of childbearing potential must have a negative serum or urine pregnancy test performed ≤ 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment and during the 3 months following completion of study treatment.
Exclusion Criteria:
-
Participants who have received > 1 prior line of chemotherapy in the advanced or metastatic setting. (Immunotherapy will not be considered a line of chemotherapy.)
-
Prior treatment with a PI3K/mTOR inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and/or necitumumab.
-
History of brain metastases unless irradiated ≥ 2 weeks prior to first study treatment and stable without requirement of corticosteroids.
-
Have serious pre-existing medical conditions.
-
Have insulin-dependent diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics.
-
Women who are pregnant or breast-feeding.
-
Clinically significant electrolyte imbalance ≥ Grade 2.
-
Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin and oral Xa inhibitors are allowed.
-
Have initiated treatment with bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents (e.g. denosumab) ≤ 28 days prior to Day 1 of Cycle 1.
-
Concurrent serious infection requiring parenteral antibiotic therapy.
-
Have a second primary malignancy that in the judgment of the investigator and Medical Monitor may affect the interpretation of results.
-
Have an active, known fungal, bacterial, and/or known viral infection.
-
History of arterial or venous embolism within 3 months prior to study enrollment. If the embolism occurred >3 and <6 months, the participant is eligible provided appropriate treatment according to institutional standard of care is ensured.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Southern Cancer Center, P.C. | Mobile | Alabama | United States | 36608 |
| 2 | Ironwood Cancer & Research Centers | Chandler | Arizona | United States | 85224 |
| 3 | Comprehensive Cancer Care and Research Institute of Colorado | Englewood | Colorado | United States | 80113 |
| 4 | Florida Cancer Specialists | Fort Myers | Florida | United States | 33916 |
| 5 | Florida Hospital Cancer Institute | Orlando | Florida | United States | 32804 |
| 6 | Florida Cancer Specialists | Saint Petersburg | Florida | United States | 33705 |
| 7 | Palm Beach Cancer Institute | West Palm Beach | Florida | United States | 33401 |
| 8 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
| 9 | Oncology Hematology Care Inc. | Cincinnati | Ohio | United States | 45242 |
| 10 | Chattanooga Oncology Hematology | Chattanooga | Tennessee | United States | 37404 |
| 11 | SMO Sarah Cannon Research Inst. | Nashville | Tennessee | United States | 37203 |
| 12 | Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
| 13 | Center for Cancer and Blood Disorders | Fort Worth | Texas | United States | 76104 |
| 14 | University of Virginia Health | Charlottesville | Virginia | United States | 22908 |
Sponsors and Collaborators
- Eli Lilly and Company
- SCRI Development Innovations, LLC
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)
More Information
Publications
None provided.- 15799
- I6A-MC-CBBE
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants completed the study if they had objective progressive disease (PD), stable disease (SD), complete response (CR) or partial response (PR). |
| Arm/Group Title | Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab |
|---|---|---|
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. |
| Period Title: Overall Study | ||
| STARTED | 15 | 16 |
| Received at Least One Dose of Study Drug | 15 | 16 |
| COMPLETED | 10 | 14 |
| NOT COMPLETED | 5 | 2 |
Baseline Characteristics
| Arm/Group Title | Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab | Total |
|---|---|---|---|
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | Total of all reporting groups |
| Overall Participants | 15 | 16 | 31 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
66.0
(10.18)
|
68.1
(5.77)
|
67.1
(8.13)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
13.3%
|
5
31.3%
|
7
22.6%
|
| Male |
13
86.7%
|
11
68.8%
|
24
77.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
15
100%
|
16
100%
|
31
100%
|
| 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 |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
6.7%
|
2
12.5%
|
3
9.7%
|
| White |
14
93.3%
|
14
87.5%
|
28
90.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
15
100%
|
16
100%
|
31
100%
|
Outcome Measures
| Title | Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at 6 Months: Disease Control Rate (DCR) |
|---|---|
| Description | RECIST v 1.1 was used to assess tumor response.The 6-month DCR was defined as the number of participants with PFS > 6 months (or 26 weeks, to accommodate the scheduled tumor assessment at week 24 be delayed by up to 2 weeks) divided by number of participants with baseline tumor assessment. Target Lesions:CR was defined as the disappearance of all target lesions. PR was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest (nadir) sum of diameters since the treatment started. Non-Target Lesions:CR was defined as disappearance of all non-target lesions and normalization of tumor markers.All lymph nodes must be non-pathological in size (<10 millimeters(mm) short axis).SD was defined as the persistence of one or more non-target lesions and/or persistence of tumor marker level above the normal limits. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab |
|---|---|---|
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. |
| Measure Participants | 15 | 16 |
| Number (95% Confidence Interval) [percentage of participants] |
6.6
44%
|
25.0
156.3%
|
| Title | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) |
|---|---|
| Description | RECIST v 1.1 was used to assess tumor response. ORR for a given participant was based on objective responses determined from data obtained up to: progression, the last evaluable assessment in the absence of progression, or initiation of subsequent anticancer therapy. Participants for whom an objective response cannot be determined or for who the best objective response is not evaluable (NE) were considered non-responders. Target Lesions: CR was defined as the disappearance of all target lesions. PR was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesions: CR was defined as disappearance of all non-target lesions and normalization of tumor markers. All lymph nodes must be non-pathological in size (<10 mm short axis). The ORR percentage was calculated as the number of participants with best objective response of CR or PR divided by the number of participants with measurable disease at baseline. |
| Time Frame | Baseline to Objective Disease Progression or Initiation of Subsequent Anticancer Therapy (Up To 3 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab |
|---|---|---|
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. |
| Measure Participants | 15 | 16 |
| Number (95% Confidence Interval) [percentage of participants] |
0.00
0%
|
0.00
0%
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from enrollment until the date of disease progression per RECIST v 1.1 or death by any cause.Participants who had not progressed or died at the time of assessment were censored at the time of the last date of tumor assessment.Participants who are enrolled but do not receive treatment and participants who have no evaluable visits will be censored on day 1.Participants who received new anti-cancer therapy before disease progression or death will be censored to the last tumor assessment date prior to the new anti-cancer therapy. Target Lesions:PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest(nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over sum. Non-Target Lesions(NTL):PD is defined as appearance of one or more new lesions and/or unequivocal progression of existing NTL. |
| Time Frame | Enrollment to Measured Progressive Disease or Death from Any Cause (Up To 12 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. Participants censored: Lead in Cohort 1 LY3023414 + Necitumumab= 4 and Post Lead in Cohort LY3023414 + Necitumumab=3 |
| Arm/Group Title | Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab |
|---|---|---|
| Arm/Group Description | LY3023414 administered orally twice daily and necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | LY3023414 administered orally twice daily and necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. |
| Measure Participants | 15 | 16 |
| Median (95% Confidence Interval) [Days] |
81
|
81
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from enrollment until the date of death by any cause. Participants lost follow up or did not die at the time of assessment were censored at the time of the last known alive date. |
| Time Frame | Enrollment to Death from Any Cause (Up To 16 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. Participants censored: Lead in Cohort 1 LY3023414 + Necitumumab=4 and Post Lead in Cohort LY3023414 + Necitumumab=9 |
| Arm/Group Title | Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab |
|---|---|---|
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. |
| Measure Participants | 15 | 16 |
| Median (95% Confidence Interval) [Days] |
102
|
279
|
| Title | Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3023414 and Necitumumab |
|---|---|
| Description | Minimum Concentration (Cmin) of LY3023414 and Necitumumab |
| Time Frame | Cycle 1 Day 8, and Cycle 3 Day 8 (pre-dose, end of necitumumab infusion and 1 hour post-necitumumab infusion), Cycle 2 Day 1, Cycle 4 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable PK data. |
| Arm/Group Title | LY3023414 | Necitumumab |
|---|---|---|
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily. | 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). |
| Measure Participants | 17 | 26 |
| Cycle 1 Day 8 |
14
(172)
|
69500
(28)
|
| Cycle 2 day 1 |
NA
(NA)
|
54000
(60)
|
| Cycle 3 Day8 |
9.73
(221)
|
121000
(36)
|
| Cycle 4 Day 1 |
NA
(NA)
|
104000
(56)
|
| Title | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023414 and Necitumumab |
|---|---|
| Description | Maximum Concentration (Cmax) of LY3023414 and Necitumumab |
| Time Frame | Cycle 1 Day 8, and Cycle 3 Day 8 (pre-dose, end of necitumumab infusion and 1 hour post-necitumumab infusion) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable PK data. |
| Arm/Group Title | LY3023414 | Necitumumab |
|---|---|---|
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily. | 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. |
| Measure Participants | 23 | 26 |
| Cycle 1 Day 8 |
738
(103)
|
318000
(27)
|
| Cycle 3 Day 8 |
1302
(70)
|
345000
(14)
|
Adverse Events
| Time Frame | Up To 330 Days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one dose of study drug. | |||
| Arm/Group Title | Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab | ||
| Arm/Group Description | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | 200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | ||
All Cause Mortality |
||||
| Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/15 (73.3%) | 6/16 (37.5%) | ||
Serious Adverse Events |
||||
| Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/15 (20%) | 5/16 (31.3%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Atrial flutter | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Constipation | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Diarrhoea | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Vomiting | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Infections and infestations | ||||
| Lung infection | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pneumonia fungal | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Nervous system disorders | ||||
| Seizure | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Vascular disorders | ||||
| Haematoma | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Hypotension | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Lead in Cohort LY3023414 + Necitumumab | Post Lead in Cohort LY3023414 + Necitumumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/15 (100%) | 16/16 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/15 (0%) | 0 | 3/16 (18.8%) | 4 |
| Increased tendency to bruise | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Leukocytosis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Thrombocytopenia | 2/15 (13.3%) | 2 | 2/16 (12.5%) | 4 |
| Cardiac disorders | ||||
| Atrial flutter | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Cyanosis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Supraventricular tachycardia | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Tachycardia | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Tricuspid valve incompetence | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Deafness | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Tinnitus | 0/15 (0%) | 0 | 2/16 (12.5%) | 2 |
| Eye disorders | ||||
| Cataract | 0/15 (0%) | 0 | 1/16 (6.3%) | 2 |
| Dry eye | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Lacrimation increased | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Vision blurred | 0/15 (0%) | 0 | 2/16 (12.5%) | 3 |
| Visual impairment | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/15 (6.7%) | 1 | 2/16 (12.5%) | 3 |
| Cheilitis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Constipation | 2/15 (13.3%) | 2 | 4/16 (25%) | 7 |
| Diarrhoea | 1/15 (6.7%) | 1 | 10/16 (62.5%) | 28 |
| Dry mouth | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Dyspepsia | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Dysphagia | 1/15 (6.7%) | 1 | 2/16 (12.5%) | 2 |
| Flatulence | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Haematochezia | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Hyperchlorhydria | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Mouth ulceration | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Nausea | 5/15 (33.3%) | 5 | 11/16 (68.8%) | 19 |
| Oral pain | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Paraesthesia oral | 1/15 (6.7%) | 2 | 0/16 (0%) | 0 |
| Stomatitis | 1/15 (6.7%) | 2 | 3/16 (18.8%) | 5 |
| Vomiting | 3/15 (20%) | 3 | 5/16 (31.3%) | 9 |
| General disorders | ||||
| Asthenia | 2/15 (13.3%) | 2 | 1/16 (6.3%) | 1 |
| Chills | 2/15 (13.3%) | 2 | 1/16 (6.3%) | 1 |
| Disease progression | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Fatigue | 7/15 (46.7%) | 8 | 11/16 (68.8%) | 17 |
| Gait disturbance | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Influenza like illness | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Mucosal inflammation | 2/15 (13.3%) | 4 | 3/16 (18.8%) | 9 |
| Oedema peripheral | 0/15 (0%) | 0 | 3/16 (18.8%) | 4 |
| Pain | 2/15 (13.3%) | 3 | 1/16 (6.3%) | 1 |
| Pyrexia | 1/15 (6.7%) | 2 | 4/16 (25%) | 5 |
| Temperature intolerance | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Thirst | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hepatobiliary disorders | ||||
| Portal vein thrombosis | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Infections and infestations | ||||
| Bronchitis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Cellulitis | 0/15 (0%) | 0 | 1/16 (6.3%) | 2 |
| Herpes zoster | 1/15 (6.7%) | 2 | 1/16 (6.3%) | 1 |
| Influenza | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Laryngitis | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Nasopharyngitis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Oral candidiasis | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Pneumonia | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pneumonia fungal | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Rash pustular | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Respiratory tract infection | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Sinusitis | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Subcutaneous abscess | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Upper respiratory tract infection | 1/15 (6.7%) | 1 | 3/16 (18.8%) | 3 |
| Urinary tract infection | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Fall | 0/15 (0%) | 0 | 2/16 (12.5%) | 2 |
| Infusion related reaction | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Skin abrasion | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase | 1/15 (6.7%) | 3 | 0/16 (0%) | 0 |
| Alanine aminotransferase increased | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Aspartate aminotransferase | 1/15 (6.7%) | 5 | 0/16 (0%) | 0 |
| Blood alkaline phosphatase | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Blood bilirubin increased | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Blood chloride decreased | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Blood creatinine increased | 0/15 (0%) | 0 | 1/16 (6.3%) | 3 |
| Blood magnesium decreased | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Blood phosphorus decreased | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Electrocardiogram qt prolonged | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Lymphocyte count decreased | 0/15 (0%) | 0 | 1/16 (6.3%) | 8 |
| Urine ketone body present | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Weight decreased | 3/15 (20%) | 4 | 4/16 (25%) | 6 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 5/15 (33.3%) | 5 | 5/16 (31.3%) | 5 |
| Dehydration | 4/15 (26.7%) | 4 | 4/16 (25%) | 4 |
| Hyperglycaemia | 1/15 (6.7%) | 2 | 3/16 (18.8%) | 4 |
| Hypernatraemia | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hypoalbuminaemia | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Hypocalcaemia | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hypokalaemia | 1/15 (6.7%) | 1 | 4/16 (25%) | 6 |
| Hypomagnesaemia | 2/15 (13.3%) | 2 | 5/16 (31.3%) | 15 |
| Hyponatraemia | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Hypophosphataemia | 0/15 (0%) | 0 | 1/16 (6.3%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Back pain | 1/15 (6.7%) | 1 | 3/16 (18.8%) | 4 |
| Bone pain | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Muscle spasms | 1/15 (6.7%) | 2 | 1/16 (6.3%) | 1 |
| Muscular weakness | 0/15 (0%) | 0 | 1/16 (6.3%) | 2 |
| Musculoskeletal chest pain | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Musculoskeletal pain | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Neck pain | 0/15 (0%) | 0 | 3/16 (18.8%) | 3 |
| Pain in extremity | 0/15 (0%) | 0 | 2/16 (12.5%) | 2 |
| Rheumatoid arthritis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Metastases to central nervous system | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Nervous system disorders | ||||
| Dizziness | 2/15 (13.3%) | 2 | 2/16 (12.5%) | 4 |
| Dysarthria | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Dysgeusia | 0/15 (0%) | 0 | 1/16 (6.3%) | 2 |
| Headache | 3/15 (20%) | 4 | 1/16 (6.3%) | 2 |
| Hypoaesthesia | 0/15 (0%) | 0 | 2/16 (12.5%) | 4 |
| Neuropathy peripheral | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Paraesthesia | 1/15 (6.7%) | 1 | 3/16 (18.8%) | 4 |
| Presyncope | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Syncope | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Tremor | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Psychiatric disorders | ||||
| Anxiety | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Confusional state | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Depression | 2/15 (13.3%) | 2 | 0/16 (0%) | 0 |
| Insomnia | 2/15 (13.3%) | 2 | 3/16 (18.8%) | 3 |
| Mental status changes | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 1 |
| Nervousness | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Restlessness | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Renal and urinary disorders | ||||
| Chromaturia | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Haematuria | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pollakiuria | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Proteinuria | 1/15 (6.7%) | 1 | 1/16 (6.3%) | 2 |
| Urinary incontinence | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchial obstruction | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Cough | 3/15 (20%) | 3 | 4/16 (25%) | 4 |
| Dysphonia | 3/15 (20%) | 4 | 2/16 (12.5%) | 4 |
| Dyspnoea | 4/15 (26.7%) | 5 | 7/16 (43.8%) | 8 |
| Epistaxis | 1/15 (6.7%) | 1 | 3/16 (18.8%) | 3 |
| Haemoptysis | 1/15 (6.7%) | 1 | 2/16 (12.5%) | 2 |
| Hiccups | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Lower respiratory tract congestion | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Nasal congestion | 0/15 (0%) | 0 | 1/16 (6.3%) | 2 |
| Nasal discomfort | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Nasal dryness | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Oropharyngeal pain | 0/15 (0%) | 0 | 4/16 (25%) | 4 |
| Paranasal sinus hypersecretion | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pleuritic pain | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Sinus congestion | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Wheezing | 0/15 (0%) | 0 | 2/16 (12.5%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Acne | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Dermatitis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Dermatitis acneiform | 8/15 (53.3%) | 13 | 4/16 (25%) | 5 |
| Dry skin | 4/15 (26.7%) | 4 | 5/16 (31.3%) | 7 |
| Ecchymosis | 0/15 (0%) | 0 | 3/16 (18.8%) | 3 |
| Erythema | 0/15 (0%) | 0 | 1/16 (6.3%) | 2 |
| Nail disorder | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Night sweats | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pruritus | 2/15 (13.3%) | 2 | 2/16 (12.5%) | 4 |
| Purpura | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Rash | 0/15 (0%) | 0 | 5/16 (31.3%) | 8 |
| Rash generalised | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Rash maculo-papular | 0/15 (0%) | 0 | 3/16 (18.8%) | 4 |
| Rash papular | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
| Skin hyperpigmentation | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Urticaria | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/15 (0%) | 0 | 2/16 (12.5%) | 2 |
| Hot flush | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hypotension | 0/15 (0%) | 0 | 2/16 (12.5%) | 2 |
| Jugular vein thrombosis | 0/15 (0%) | 0 | 1/16 (6.3%) | 1 |
| Superior vena cava syndrome | 1/15 (6.7%) | 1 | 0/16 (0%) | 0 |
Limitations/Caveats
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 |
| ClinicalTrials.gov@lilly.com |
- 15799
- I6A-MC-CBBE