A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02178358
Collaborator
(none)
132
16
3
78.4
8.3
0.1
Study Details
Study Description
Brief Summary
The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2157299 in participants with hepatocellular carcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
132 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase 2 Study of LY2157299 Versus LY2157299 - Sorafenib Combination Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Actual Study Start Date
:
Aug 8, 2014
Actual Primary Completion Date
:
Jun 30, 2017
Actual Study Completion Date
:
Feb 18, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 150 milligram (mg) Galunisertib Monotherapy 150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle). |
Drug: LY2157299
Administered orally
|
| Experimental: 150 mg Galunisertib + 400 mg Sorafenib Therapy 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
Drug: LY2157299
Administered orally
Drug: Sorafenib
Administered orally
|
| Placebo Comparator: 400 mg Sorafenib + Placebo Therapy Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
Drug: Sorafenib
Administered orally
Drug: Placebo
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS): Number of Events [Randomization to Date of Death from Any Cause (Up To 24 Months)]
OS defined as the time from the date of randomization to the date of death due to any cause. An overall survival event was defined as death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The number of participants with overall survival events (deaths) is reported.
Secondary Outcome Measures
- Population Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib [Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1]
Population mean (between-subject coefficient variance [CV %]) apparent clearance.
- Population Pharmacokinetics (PopPK): Steady State Apparent Volume of Distribution (Vss) of Galunisertib [Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1]
Population Vss [distribution of galunisertib in the body at steady state] after a single dose of galunisertib.
- Time to Tumor Progression (TTP) [Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up To 24 Months)]
TTP at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
- Progression-Free Survival (PFS) [Randomization to Measured Progressive Disease or Death (Up To 24 Months)]
PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was 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 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. 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 adequate tumor assessment date.
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [Randomization to Measured Progressive Disease (Up To 24 Months)]
ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was 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 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Score [Baseline, 24 Months]
EORTC QLQ-C30 consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much). Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.
- Change From Baseline in EORTC QLQ Hepatocellular Carcinoma (HCC-18) Questionnaire Score [Baseline, 24 Months]
The EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as abdominal swelling, sex life, fatigue, body image, jaundice, nutrition, pain and fever. Each individual item ranges from 1 to 4, where 1 = "not at all" and 4 = "very much." All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a symptom scale/item represented a high level of symptomatology/problem.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have histological evidence of a diagnosis of HCC not amenable to curative surgery.
-
Have Child-Pugh Class A.
-
Have the presence of measurable disease.
-
Have adequate organ function.
-
Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
-
If male or female with reproductive potential, must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug.
-
If females with childbearing potential, must have had a negative serum pregnancy test 7 days prior to the first dose of study drug.
-
Are able to swallow capsules or tablets.
-
Have available diagnostic or biopsy tumor tissue.
Exclusion Criteria:
-
Have received previous systemic treatment for advanced disease.
-
Have known HCC with fibro-lamellar or mixed histology.
-
Have presence of clinically relevant ascites.
-
Have had a liver transplant.
-
Have moderate or severe cardiac disease.
-
Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.
-
Have experienced Grade 3 or 4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention.
-
Have esophageal or gastric varices that require immediate intervention or represent a high bleeding risk.
-
Had major surgery within 4 weeks prior to the study randomization.
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. | Beijing | China | 100036 | |
| 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. | Bengbu | China | 233004 | |
| 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. | Changchun | China | 130012 | |
| 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. | Hangzhou | China | 310016 | |
| 5 | 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. | Hefei | China | 230022 | |
| 6 | 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. | Hong Kong | Hong Kong | ||
| 7 | 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. | Kowloon | Hong Kong | ||
| 8 | 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. | Incheon | Korea, Republic of | 405-760 | |
| 9 | 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. | Seoul | Korea, Republic of | 135 720 | |
| 10 | 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. | Gwei Shan Township | Taiwan | 333 | |
| 11 | 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. | Liouying/Tainan | Taiwan | 736 | |
| 12 | 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. | Puzih City | Taiwan | 613 | |
| 13 | 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. | Tainan | Taiwan | 70403 | |
| 14 | 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. | Taipei | Taiwan | 11217 | |
| 15 | 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. | Taoyuan | Taiwan | 33378 | |
| 16 | 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. | Bangkok | Thailand | 10330 |
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 - hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02178358
Other Study ID Numbers:
- 15065
- H9H-MC-JBAS
First Posted:
Jun 30, 2014
Last Update Posted:
Feb 25, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | In the Participant Flow, participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment. |
| Arm/Group Title | 150 Milligram (mg) Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy |
|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Period Title: Overall Study | |||
| STARTED | 20 | 74 | 38 |
| Received at Least 1 Dose of Study Drug | 20 | 74 | 38 |
| COMPLETED | 19 | 72 | 36 |
| NOT COMPLETED | 1 | 2 | 2 |
Baseline Characteristics
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy | Total |
|---|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Total of all reporting groups |
| Overall Participants | 20 | 74 | 38 | 132 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
13
65%
|
55
74.3%
|
28
73.7%
|
96
72.7%
|
| >=65 years |
7
35%
|
19
25.7%
|
10
26.3%
|
36
27.3%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
60.6
(7.8)
|
59.0
(8.5)
|
58.6
(11.8)
|
59.1
(9.4)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
4
20%
|
12
16.2%
|
1
2.6%
|
17
12.9%
|
| Male |
16
80%
|
62
83.8%
|
37
97.4%
|
115
87.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
20
100%
|
74
100%
|
38
100%
|
132
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| South Korea |
7
35%
|
33
44.6%
|
13
34.2%
|
53
40.2%
|
| Hong Kong |
6
30%
|
10
13.5%
|
6
15.8%
|
22
16.7%
|
| China |
0
0%
|
15
20.3%
|
8
21.1%
|
23
17.4%
|
| Taiwan |
7
35%
|
11
14.9%
|
9
23.7%
|
27
20.5%
|
| Thailand |
0
0%
|
5
6.8%
|
2
5.3%
|
7
5.3%
|
| Weight (kilogram (kg)) [Median (Full Range) ] | ||||
| Median (Full Range) [kilogram (kg)] |
66.400
|
63.575
|
62.400
|
63.575
|
| Height (Centimeter (cm)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Centimeter (cm)] |
162.84
(7.38)
|
165.30
(7.50)
|
166.55
(5.69)
|
165.29
(7.05)
|
| BMI (kilogram per square metre (kg/m2)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kilogram per square metre (kg/m2)] |
24.806
(4.105)
|
23.224
(3.248)
|
22.843
(3.062)
|
23.354
(3.373)
|
| Tobacco use (Count of Participants) | ||||
| Never |
7
35%
|
28
37.8%
|
11
28.9%
|
46
34.8%
|
| Former |
7
35%
|
35
47.3%
|
22
57.9%
|
64
48.5%
|
| Current |
6
30%
|
11
14.9%
|
5
13.2%
|
22
16.7%
|
| Alcohol use (Count of Participants) | ||||
| Never |
7
35%
|
29
39.2%
|
16
42.1%
|
52
39.4%
|
| Former |
0
0%
|
1
1.4%
|
2
5.3%
|
3
2.3%
|
| Current |
13
65%
|
44
59.5%
|
20
52.6%
|
77
58.3%
|
| Alcohol drinks per week (Standard alcohol drinks per week) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Standard alcohol drinks per week] |
5.7
(7.2)
|
3.3
(4.7)
|
2.3
(2.8)
|
3.4
(4.8)
|
Outcome Measures
| Title | Overall Survival (OS): Number of Events |
|---|---|
| Description | OS defined as the time from the date of randomization to the date of death due to any cause. An overall survival event was defined as death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The number of participants with overall survival events (deaths) is reported. |
| Time Frame | Randomization to Date of Death from Any Cause (Up To 24 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Censored participants: Galunisertib Monotherapy =5, Galunisertib Plus Sorafenib Therapy = 16 and Sorafenib Plus Placebo Therapy = 7. |
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy |
|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 20 | 74 | 38 |
| Number [Participants with events] |
15
75%
|
58
78.4%
|
31
81.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 150 mg Galunisertib Monotherapy, 400 mg Sorafenib + Placebo Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.837 |
| Comments | ||
| Method | Bayesian exponential-likelihood model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.776 | |
| Confidence Interval |
(2-Sided) 95% 0.434 to 1.226 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 150 mg Galunisertib + 400 mg Sorafenib Therapy, 400 mg Sorafenib + Placebo Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.704 |
| Comments | ||
| Method | Bayesian exponential-likelihood model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.917 | |
| Confidence Interval |
(2-Sided) 95% 0.633 to 1.266 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Population Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib |
|---|---|
| Description | Population mean (between-subject coefficient variance [CV %]) apparent clearance. |
| Time Frame | Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug, with evaluable galunisertib PK data. The analyses conducted on galunisertib exposure parameter from both arms combined per the statistical analysis plan, as monotherapy and combination arm showed no difference in galunisertib PK. |
| Arm/Group Title | Galunisertib Monotherapy and Galunisertib + Sorafenib Therapy |
|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 91 |
| Geometric Mean (Geometric Coefficient of Variation) [Liter per hour (L/hr)] |
33.6
(48)
|
| Title | Population Pharmacokinetics (PopPK): Steady State Apparent Volume of Distribution (Vss) of Galunisertib |
|---|---|
| Description | Population Vss [distribution of galunisertib in the body at steady state] after a single dose of galunisertib. |
| Time Frame | Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug, with evaluable galunisertib PK data. The analyses conducted on galunisertib exposure parameter from both arms combined per the statistical analysis plan, as monotherapy and combination arm showed no difference in galunisertib PK. |
| Arm/Group Title | Galunisertib Monotherapy and Galunisertib + Sorafenib Therapy |
|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 91 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters (L)] |
192
(69)
|
| Title | Time to Tumor Progression (TTP) |
|---|---|
| Description | TTP at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Time Frame | Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up To 24 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Censored participants: Galunisertib Monotherapy =2, Galunisertib Plus Sorafenib Therapy = 15 and Sorafenib Plus Placebo Therapy = 9. |
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy |
|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 20 | 74 | 38 |
| Median (95% Confidence Interval) [Months] |
1.41
|
2.86
|
4.14
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was 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 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. 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 adequate tumor assessment date. |
| Time Frame | Randomization to Measured Progressive Disease or Death (Up To 24 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Censored participants: Galunisertib Monotherapy =1, Galunisertib Plus Sorafenib Therapy = 8 and Sorafenib Plus Placebo Therapy = 5. |
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy |
|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 20 | 74 | 38 |
| Median (99% Confidence Interval) [Months] |
1.41
|
2.86
|
4.14
|
| Title | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) |
|---|---|
| Description | ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was 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 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. |
| Time Frame | Randomization to Measured Progressive Disease (Up To 24 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy |
|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 20 | 74 | 38 |
| Number (95% Confidence Interval) [Percentage of participants] |
0.05
0.3%
|
0.027
0%
|
0.158
0.4%
|
| Title | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Score |
|---|---|
| Description | EORTC QLQ-C30 consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much). Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem. |
| Time Frame | Baseline, 24 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and with baseline and post-baseline EORTC QLQ-C30 data for each EORTC QLQ-C30 items. |
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy |
|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 19 | 65 | 35 |
| Global health status |
43.42
(23.171)
|
55.90
(22.473)
|
58.57
(17.326)
|
| Functional scale: Physical functioning |
84.56
(16.338)
|
82.87
(19.613)
|
80.95
(16.580)
|
| Functional scale: Role functioning |
89.47
(14.918)
|
82.05
(24.880)
|
85.24
(19.289)
|
| Functional Scale: Emotional Functioning |
84.65
(18.271)
|
87.18
(17.247)
|
86.90
(13.898)
|
| Functional Scale: Cognitive Functioning |
89.47
(16.860)
|
91.03
(14.754)
|
85.71
(18.142)
|
| Functional Scale: Social Functioning |
83.33
(24.845)
|
84.10
(19.859)
|
84.29
(18.052)
|
| Symptom Scale: Fatigue |
21.05
(23.393)
|
24.10
(22.444)
|
25.40
(18.390)
|
| Symptom Scale: Nausea and Vomiting |
2.63
(8.358)
|
3.85
(8.725)
|
3.33
(8.856)
|
| Symptom scale: Pain |
17.54
(19.621)
|
17.18
(25.340)
|
14.76
(20.521)
|
| Symptom scale: Dyspnoea |
17.54
(28.040)
|
11.79
(19.922)
|
12.38
(18.232)
|
| Symptom scale: Insomnia |
21.05
(31.838)
|
9.74
(19.296)
|
16.19
(16.903)
|
| Symptom scale: Appetite loss |
15.79
(25.744)
|
16.92
(25.768)
|
18.10
(23.351)
|
| Symptom scale: Constipation |
5.26
(12.488)
|
6.15
(13.033)
|
6.67
(15.760)
|
| Symptom scale: Diarrhoea |
10.53
(19.413)
|
4.62
(13.013)
|
10.48
(17.660)
|
| Symptom scale: Financial difficulties |
15.79
(25.744)
|
23.08
(26.954)
|
20.95
(22.989)
|
| Title | Change From Baseline in EORTC QLQ Hepatocellular Carcinoma (HCC-18) Questionnaire Score |
|---|---|
| Description | The EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as abdominal swelling, sex life, fatigue, body image, jaundice, nutrition, pain and fever. Each individual item ranges from 1 to 4, where 1 = "not at all" and 4 = "very much." All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a symptom scale/item represented a high level of symptomatology/problem. |
| Time Frame | Baseline, 24 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC-QLQ HCC-18 data for each EORTC-QLQ HCC-18 items. |
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy |
|---|---|---|---|
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| Measure Participants | 19 | 65 | 35 |
| Abdominal swelling |
24.56
(33.040)
|
32.82
(31.453)
|
27.62
(24.899)
|
| Sex Life |
28.07
(31.940)
|
58.97
(35.242)
|
46.08
(35.783)
|
| Fatigue |
32.16
(21.563)
|
47.86
(29.128)
|
46.98
(26.278)
|
| Body Image |
28.07
(26.089)
|
36.15
(22.930)
|
31.90
(20.758)
|
| Jaundice |
20.18
(25.202)
|
27.69
(25.392)
|
25.24
(21.531)
|
| Nutrition |
22.46
(21.223)
|
34.05
(23.456)
|
34.48
(18.611)
|
| Pain |
25.44
(18.732)
|
25.38
(21.471)
|
30.95
(21.822)
|
| Fever |
14.04
(16.909)
|
25.38
(25.019)
|
20.48
(20.646)
|
Adverse Events
| Time Frame | Up To 63 Months | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. | |||||
| Arm/Group Title | 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy | |||
| Arm/Group Description | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. | |||
All Cause Mortality |
||||||
| 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/20 (75%) | 58/74 (78.4%) | 31/38 (81.6%) | |||
Serious Adverse Events |
||||||
| 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/20 (30%) | 31/74 (41.9%) | 11/38 (28.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/20 (0%) | 0 | 2/74 (2.7%) | 2 | 0/38 (0%) | 0 |
| Febrile neutropenia | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Leukopenia | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Lymphadenopathy | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Cardiac disorders | ||||||
| Myocardial infarction | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Hearing impaired | 1/20 (5%) | 1 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Vertigo | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Abdominal pain | 0/20 (0%) | 0 | 3/74 (4.1%) | 4 | 2/38 (5.3%) | 2 |
| Ascites | 0/20 (0%) | 0 | 2/74 (2.7%) | 2 | 1/38 (2.6%) | 2 |
| Diarrhoea | 0/20 (0%) | 0 | 2/74 (2.7%) | 2 | 1/38 (2.6%) | 1 |
| Duodenal ulcer haemorrhage | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Food poisoning | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Gastritis | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Gastritis haemorrhagic | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/20 (0%) | 0 | 2/74 (2.7%) | 2 | 0/38 (0%) | 0 |
| Haematochezia | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Haemorrhoidal haemorrhage | 1/20 (5%) | 3 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Haemorrhoids | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Nausea | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Oesophageal varices haemorrhage | 1/20 (5%) | 1 | 3/74 (4.1%) | 3 | 0/38 (0%) | 0 |
| Rectal haemorrhage | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/20 (0%) | 0 | 4/74 (5.4%) | 4 | 0/38 (0%) | 0 |
| Varices oesophageal | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| General disorders | ||||||
| Chest pain | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Fatigue | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Oedema peripheral | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Pyrexia | 0/20 (0%) | 0 | 4/74 (5.4%) | 6 | 0/38 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholangitis | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 2 |
| Hepatic failure | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Hepatic haemorrhage | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Jaundice | 1/20 (5%) | 1 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Infections and infestations | ||||||
| Anal infection | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Biliary tract infection | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Cellulitis | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Endocarditis bacterial | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Influenza | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Oesophageal candidiasis | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Pneumonia | 1/20 (5%) | 1 | 1/74 (1.4%) | 1 | 1/38 (2.6%) | 1 |
| Sepsis | 1/20 (5%) | 1 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Streptococcal sepsis | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Hepatic rupture | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Investigations | ||||||
| Blood bilirubin increased | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 2 |
| Platelet count decreased | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Troponin i increased | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Hypoalbuminaemia | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Hypoglycaemia | 1/20 (5%) | 1 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Neck pain | 1/20 (5%) | 1 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Nervous system disorders | ||||||
| Cerebral haemorrhage | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 1/38 (2.6%) | 1 |
| Dizziness | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Haemorrhage intracranial | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Hepatic encephalopathy | 1/20 (5%) | 1 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Azotaemia | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 1/38 (2.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pneumonia aspiration | 1/20 (5%) | 1 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Rash maculo-papular | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Urticaria | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
| Vascular disorders | ||||||
| Shock | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 0/38 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| 150 mg Galunisertib Monotherapy | 150 mg Galunisertib + 400 mg Sorafenib Therapy | 400 mg Sorafenib + Placebo Therapy | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/20 (85%) | 73/74 (98.6%) | 38/38 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/20 (10%) | 3 | 17/74 (23%) | 26 | 7/38 (18.4%) | 7 |
| Thrombocytopenia | 0/20 (0%) | 0 | 1/74 (1.4%) | 2 | 3/38 (7.9%) | 3 |
| Cardiac disorders | ||||||
| Palpitations | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 2 |
| Endocrine disorders | ||||||
| Hyperthyroidism | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 2/38 (5.3%) | 2 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 6/20 (30%) | 6 | 8/74 (10.8%) | 10 | 4/38 (10.5%) | 5 |
| Abdominal pain | 5/20 (25%) | 6 | 16/74 (21.6%) | 18 | 7/38 (18.4%) | 7 |
| Abdominal pain upper | 1/20 (5%) | 1 | 1/74 (1.4%) | 1 | 4/38 (10.5%) | 6 |
| Ascites | 3/20 (15%) | 3 | 6/74 (8.1%) | 6 | 4/38 (10.5%) | 4 |
| Constipation | 2/20 (10%) | 3 | 10/74 (13.5%) | 11 | 7/38 (18.4%) | 10 |
| Diarrhoea | 5/20 (25%) | 8 | 29/74 (39.2%) | 51 | 22/38 (57.9%) | 50 |
| Dyspepsia | 2/20 (10%) | 2 | 7/74 (9.5%) | 9 | 1/38 (2.6%) | 1 |
| Nausea | 1/20 (5%) | 1 | 14/74 (18.9%) | 15 | 4/38 (10.5%) | 4 |
| Stomatitis | 0/20 (0%) | 0 | 7/74 (9.5%) | 10 | 10/38 (26.3%) | 13 |
| Toothache | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 3 |
| Vomiting | 2/20 (10%) | 2 | 15/74 (20.3%) | 19 | 4/38 (10.5%) | 8 |
| General disorders | ||||||
| Asthenia | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 2 |
| Chills | 1/20 (5%) | 1 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 2 |
| Fatigue | 6/20 (30%) | 8 | 23/74 (31.1%) | 28 | 14/38 (36.8%) | 16 |
| Influenza like illness | 2/20 (10%) | 3 | 7/74 (9.5%) | 8 | 1/38 (2.6%) | 2 |
| Malaise | 0/20 (0%) | 0 | 4/74 (5.4%) | 6 | 3/38 (7.9%) | 4 |
| Mucosal inflammation | 0/20 (0%) | 0 | 4/74 (5.4%) | 4 | 1/38 (2.6%) | 1 |
| Non-cardiac chest pain | 1/20 (5%) | 1 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 2 |
| Oedema | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 2/38 (5.3%) | 2 |
| Oedema peripheral | 2/20 (10%) | 2 | 4/74 (5.4%) | 4 | 6/38 (15.8%) | 6 |
| Pain | 1/20 (5%) | 1 | 4/74 (5.4%) | 4 | 1/38 (2.6%) | 1 |
| Pyrexia | 1/20 (5%) | 3 | 26/74 (35.1%) | 43 | 5/38 (13.2%) | 5 |
| Infections and infestations | ||||||
| Rash pustular | 1/20 (5%) | 1 | 4/74 (5.4%) | 4 | 3/38 (7.9%) | 3 |
| Upper respiratory tract infection | 0/20 (0%) | 0 | 2/74 (2.7%) | 2 | 5/38 (13.2%) | 6 |
| Investigations | ||||||
| Alanine aminotransferase increased | 2/20 (10%) | 2 | 23/74 (31.1%) | 40 | 15/38 (39.5%) | 24 |
| Aspartate aminotransferase increased | 2/20 (10%) | 2 | 26/74 (35.1%) | 42 | 15/38 (39.5%) | 25 |
| Blood alkaline phosphatase increased | 0/20 (0%) | 0 | 10/74 (13.5%) | 12 | 3/38 (7.9%) | 4 |
| Blood bilirubin increased | 2/20 (10%) | 2 | 11/74 (14.9%) | 15 | 15/38 (39.5%) | 22 |
| Blood creatine phosphokinase increased | 0/20 (0%) | 0 | 5/74 (6.8%) | 8 | 3/38 (7.9%) | 9 |
| Blood lactate dehydrogenase increased | 0/20 (0%) | 0 | 8/74 (10.8%) | 12 | 3/38 (7.9%) | 3 |
| Gamma-glutamyltransferase increased | 0/20 (0%) | 0 | 9/74 (12.2%) | 9 | 5/38 (13.2%) | 7 |
| Lipase increased | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 5 |
| Lymphocyte count decreased | 0/20 (0%) | 0 | 4/74 (5.4%) | 5 | 1/38 (2.6%) | 1 |
| Neutrophil count decreased | 1/20 (5%) | 1 | 9/74 (12.2%) | 14 | 4/38 (10.5%) | 4 |
| Platelet count decreased | 0/20 (0%) | 0 | 19/74 (25.7%) | 35 | 13/38 (34.2%) | 21 |
| Thyroxine increased | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 2/38 (5.3%) | 2 |
| Weight decreased | 2/20 (10%) | 2 | 5/74 (6.8%) | 6 | 6/38 (15.8%) | 6 |
| White blood cell count decreased | 0/20 (0%) | 0 | 4/74 (5.4%) | 6 | 5/38 (13.2%) | 10 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/20 (15%) | 3 | 27/74 (36.5%) | 28 | 12/38 (31.6%) | 15 |
| Hyperglycaemia | 2/20 (10%) | 2 | 2/74 (2.7%) | 5 | 2/38 (5.3%) | 3 |
| Hypoalbuminaemia | 1/20 (5%) | 1 | 7/74 (9.5%) | 7 | 9/38 (23.7%) | 10 |
| Hypocalcaemia | 0/20 (0%) | 0 | 6/74 (8.1%) | 6 | 5/38 (13.2%) | 7 |
| Hypokalaemia | 1/20 (5%) | 1 | 10/74 (13.5%) | 16 | 4/38 (10.5%) | 6 |
| Hypomagnesaemia | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 6/38 (15.8%) | 9 |
| Hyponatraemia | 1/20 (5%) | 1 | 5/74 (6.8%) | 6 | 7/38 (18.4%) | 10 |
| Hypophosphataemia | 2/20 (10%) | 2 | 33/74 (44.6%) | 74 | 13/38 (34.2%) | 23 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/20 (5%) | 1 | 2/74 (2.7%) | 2 | 2/38 (5.3%) | 2 |
| Back pain | 1/20 (5%) | 1 | 3/74 (4.1%) | 3 | 3/38 (7.9%) | 3 |
| Musculoskeletal pain | 0/20 (0%) | 0 | 2/74 (2.7%) | 3 | 4/38 (10.5%) | 4 |
| Myalgia | 0/20 (0%) | 0 | 2/74 (2.7%) | 2 | 4/38 (10.5%) | 4 |
| Nervous system disorders | ||||||
| Dizziness | 0/20 (0%) | 0 | 5/74 (6.8%) | 5 | 4/38 (10.5%) | 7 |
| Headache | 3/20 (15%) | 3 | 7/74 (9.5%) | 8 | 1/38 (2.6%) | 1 |
| Peripheral sensory neuropathy | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 2/38 (5.3%) | 2 |
| Psychiatric disorders | ||||||
| Insomnia | 1/20 (5%) | 1 | 6/74 (8.1%) | 6 | 3/38 (7.9%) | 3 |
| Renal and urinary disorders | ||||||
| Proteinuria | 1/20 (5%) | 1 | 7/74 (9.5%) | 10 | 6/38 (15.8%) | 9 |
| Reproductive system and breast disorders | ||||||
| Genital disorder female | 0/4 (0%) | 0 | 1/12 (8.3%) | 1 | 0/1 (0%) | 0 |
| Genital rash | 0/20 (0%) | 0 | 0/74 (0%) | 0 | 2/38 (5.3%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 3/20 (15%) | 3 | 8/74 (10.8%) | 9 | 6/38 (15.8%) | 6 |
| Dysphonia | 0/20 (0%) | 0 | 6/74 (8.1%) | 7 | 5/38 (13.2%) | 5 |
| Dyspnoea | 2/20 (10%) | 2 | 6/74 (8.1%) | 6 | 6/38 (15.8%) | 6 |
| Epistaxis | 0/20 (0%) | 0 | 3/74 (4.1%) | 3 | 3/38 (7.9%) | 4 |
| Haemoptysis | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 3/38 (7.9%) | 4 |
| Oropharyngeal pain | 1/20 (5%) | 1 | 4/74 (5.4%) | 4 | 6/38 (15.8%) | 7 |
| Pleural effusion | 0/20 (0%) | 0 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 2 |
| Productive cough | 1/20 (5%) | 1 | 1/74 (1.4%) | 1 | 2/38 (5.3%) | 3 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/20 (0%) | 0 | 15/74 (20.3%) | 15 | 7/38 (18.4%) | 7 |
| Dermatitis acneiform | 0/20 (0%) | 0 | 13/74 (17.6%) | 18 | 6/38 (15.8%) | 7 |
| Dry skin | 1/20 (5%) | 1 | 2/74 (2.7%) | 2 | 2/38 (5.3%) | 2 |
| Erythema | 0/20 (0%) | 0 | 4/74 (5.4%) | 4 | 1/38 (2.6%) | 1 |
| Erythema multiforme | 2/20 (10%) | 2 | 0/74 (0%) | 0 | 0/38 (0%) | 0 |
| Palmar-plantar erythrodysaesthesia syndrome | 4/20 (20%) | 5 | 42/74 (56.8%) | 57 | 19/38 (50%) | 25 |
| Pruritus | 3/20 (15%) | 3 | 13/74 (17.6%) | 20 | 4/38 (10.5%) | 5 |
| Rash | 1/20 (5%) | 1 | 20/74 (27%) | 24 | 9/38 (23.7%) | 10 |
| Rash maculo-papular | 1/20 (5%) | 1 | 7/74 (9.5%) | 11 | 3/38 (7.9%) | 4 |
| Vascular disorders | ||||||
| Hypertension | 0/20 (0%) | 0 | 15/74 (20.3%) | 15 | 4/38 (10.5%) | 4 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The 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 of less than 90 days from the time submitted to the sponsor for review.The PI will remove from publication the information which the sponsor reasonably thinks would jeopardize its intellectual property interests or delay the publication until the publication no longer jeopardizes its intellectual property interests.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| clinicaltrials.gov@lilly.com |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02178358
Other Study ID Numbers:
- 15065
- H9H-MC-JBAS
First Posted:
Jun 30, 2014
Last Update Posted:
Feb 25, 2022
Last Verified:
Feb 1, 2022