A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02518113
Collaborator
(none)
36
22
4
27.5
1.6
0.1
Study Details
Study Description
Brief Summary
The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with dexamethasone in participants with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma (T-ALL/T-LBL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
36 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients
Actual Study Start Date
:
Oct 1, 2015
Actual Primary Completion Date
:
Jan 15, 2018
Actual Study Completion Date
:
Jan 15, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY3039478 + Dexamethasone (Adult) Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
Drug: LY3039478
Administered orally
Drug: Dexamethasone
Administered orally
|
| Experimental: LY3039478 + Dexamethasone (Pediatric) Part B: LY3039478 administered orally TIW at escalating doses and dexamethasone administered orally twice a day (BID) on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Part B of the study. |
Drug: LY3039478
Administered orally
Drug: Dexamethasone
Administered orally
|
| Experimental: Phase 2: LY3039478 + Dexamethasone LY3039478 administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Phase 2 of the study. |
Drug: LY3039478
Administered orally
Drug: Dexamethasone
Administered orally
|
| Placebo Comparator: Phase 2: Placebo + Dexamethasone Placebo administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Phase 2 of the study. |
Drug: Dexamethasone
Administered orally
Drug: Placebo
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities (DLTs) [Cycle 1 (Up To 28 Days)]
A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria: CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of the patient from the study during Cycle 1).
- Recommended Dose of LY3039478 in Combination With Dexamethasone [Cycle 1 (28 Days)]
A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria:CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting.A dose-limiting equivalent toxicity (DLET) was defined as an AE occurring between Day 1 and Day 28 of any cycle (other than Cycle 1) for a patient enrolled in the Phase 1 portion or in any cycle (including Cycle 1) for a patient enrolled in the Phase 2 portion that would have met the criteria for DLT if it had occurred during Cycle 1 for a patient enrolled in the Phase 1 portion.
- Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR) [Baseline to Objective Disease Progression (Up To 2 Months)]
ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of patients achieving a CR or a CRi divided by the total number of patients randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm.
Secondary Outcome Measures
- Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination With Dexamethasone in Day 1 [Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours]
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination with Dexamethasone in Day 1
- Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8 [Cycle 1 Day 8: Predose, 1-2, 3-4,6-8,24-30 hours]
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination with Dexamethasone in Day 8
- Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations [Baseline to Objective Disease Progression (Up To 12 Months)]
ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of participants achieving a CR or a CRi divided by the total number of participants randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm.
- Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR [Baseline to Objective Disease Progression (Up To 12 Months)]
- Phase 2: Number of Participants Who Achieve PR [Baseline to Objective Disease Progression (Up To 12 Months)]
- Phase 2: Duration of Remission (DoR) [Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year)]
- Phase 2:Relapse Free Survival (RFS) [Date of CR to Relapse or Death from any Cause (Approximately 1 Year)]
- Phase 2: Event Free Survival (EFS) [Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year)]
- Phase 2: Overall Survival (OS) [Baseline to the Date of Death from Any Cause (Approximately 1.5 Years)]
- Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score [Baseline, End of Study (Approximately 1.5 Years)]
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have acute T-cell lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
-
T-ALL or T-LBL participants with relapsed/refractory disease.
-
Have had at least 60 days between prior hematopoietic stem cell transplantation (SCT) and first dose of study drug.
-
Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale for adults.
-
Lansky score >50% for participants <16 years old.
-
Have adequate organ function.
-
Are at least:
-
adult Phase 1 Part A and Phase 2: ≥16 years old at the time of screening
-
pediatric Phase 1 Part B: 2 to <16 years old
-
Men and women with reproductive potential: Must agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug(s) or country requirements, whichever is longer.
-
Females with childbearing potential: Have had a negative serum pregnancy test ≤7 days before the first dose of study drug and also must not be breastfeeding.
-
Are able to swallow capsules and tablets.
Exclusion Criteria:
-
Have previously completed or withdrawn from this study or any other study investigating LY3039478 or other Notch inhibitors.
-
Have evidence of uncontrolled, active infection <7 days prior to administration of study medication.
-
Have current or recent gastrointestinal disease with chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease.
-
Have active leukemic involvement of the central nervous system (CNS).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope National Medical Center | Duarte | California | United States | 91010-0269 |
| 2 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 3 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 4 | Montefiore Medical Center | Bronx | New York | United States | 10467 |
| 5 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 6 | University of Pennsylvania Hospital | Philadelphia | Pennsylvania | United States | 19106 |
| 7 | University of Texas MD Anderson | Houston | Texas | United States | 77030 |
| 8 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | LIlle | France | 59037 | |
| 9 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Nantes | France | 44093 | |
| 10 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Paris | France | 75475 | |
| 11 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Pierre Benite | France | 69495 | |
| 12 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Toulouse | France | 31059 | |
| 13 | Johann Wolfgang Goethe-Universität Frankfurt | Frankfurt | Germany | 60590 | |
| 14 | Universitätsklinikum Heidelberg | Heidelberg | Germany | 69120 | |
| 15 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Ulm | Germany | 89081 | |
| 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. | Haifa | Israel | 3525408 | |
| 17 | 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. | Jerusalem | Israel | 9112001 | |
| 18 | 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. | Ramat Gan | Israel | 5266202 | |
| 19 | 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. | Tel Aviv | Israel | 6423906 | |
| 20 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Milano | Italy | 20132 | |
| 21 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Napoli | Italy | 80131 | |
| 22 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. | Torino | Italy | 10126 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02518113
Other Study ID Numbers:
- 14548
- I6F-MC-JJCB
- 2014-005024-10
First Posted:
Aug 7, 2015
Last Update Posted:
Sep 11, 2019
Last Verified:
Aug 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Study completers are those participants that completed Part A cycle 1 or experienced a DLT. There were no participants enrolled to Part B and Phase 2 of the study. |
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Period Title: Overall Study | ||||
| STARTED | 6 | 12 | 15 | 3 |
| COMPLETED | 3 | 7 | 11 | 3 |
| NOT COMPLETED | 3 | 5 | 4 | 0 |
Baseline Characteristics
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Total of all reporting groups |
| Overall Participants | 6 | 12 | 15 | 3 | 36 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
38.83
(12.22)
|
36.42
(13.40)
|
45.87
(14.41)
|
26.67
(10.69)
|
39.94
(14.21)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
0
0%
|
5
41.7%
|
5
33.3%
|
1
33.3%
|
11
30.6%
|
| Male |
6
100%
|
7
58.3%
|
10
66.7%
|
2
66.7%
|
25
69.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
16.7%
|
1
8.3%
|
1
6.7%
|
1
33.3%
|
4
11.1%
|
| Not Hispanic or Latino |
4
66.7%
|
8
66.7%
|
11
73.3%
|
2
66.7%
|
25
69.4%
|
| Unknown or Not Reported |
1
16.7%
|
3
25%
|
3
20%
|
0
0%
|
7
19.4%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
1
2.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
8.3%
|
1
6.7%
|
0
0%
|
2
5.6%
|
| White |
5
83.3%
|
10
83.3%
|
12
80%
|
3
100%
|
30
83.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
16.7%
|
0
0%
|
2
13.3%
|
0
0%
|
3
8.3%
|
| Region of Enrollment (Count of Participants) | |||||
| United States |
2
33.3%
|
7
58.3%
|
7
46.7%
|
1
33.3%
|
17
47.2%
|
| Italy |
0
0%
|
0
0%
|
2
13.3%
|
2
66.7%
|
4
11.1%
|
| France |
3
50%
|
4
33.3%
|
4
26.7%
|
0
0%
|
11
30.6%
|
| Germany |
1
16.7%
|
1
8.3%
|
2
13.3%
|
0
0%
|
4
11.1%
|
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria: CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of the patient from the study during Cycle 1). |
| Time Frame | Cycle 1 (Up To 28 Days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug in Part A. |
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 6 | 12 | 15 | 3 |
| Count of Participants [Participants] |
0
0%
|
2
16.7%
|
2
13.3%
|
3
100%
|
| Title | Recommended Dose of LY3039478 in Combination With Dexamethasone |
|---|---|
| Description | A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria:CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting.A dose-limiting equivalent toxicity (DLET) was defined as an AE occurring between Day 1 and Day 28 of any cycle (other than Cycle 1) for a patient enrolled in the Phase 1 portion or in any cycle (including Cycle 1) for a patient enrolled in the Phase 2 portion that would have met the criteria for DLT if it had occurred during Cycle 1 for a patient enrolled in the Phase 1 portion. |
| Time Frame | Cycle 1 (28 Days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug in Part A. |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 36 |
| Number [mg] |
75
|
| Title | Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR) |
|---|---|
| Description | ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of patients achieving a CR or a CRi divided by the total number of patients randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm. |
| Time Frame | Baseline to Objective Disease Progression (Up To 2 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug in Part A. |
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 6 | 12 | 15 | 3 |
| Count of Participants [Participants] |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination With Dexamethasone in Day 1 |
|---|---|
| Description | Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination with Dexamethasone in Day 1 |
| Time Frame | Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug in Part A and had evaluable PK data. |
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 5 | 12 | 15 | 2 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram hour per milliliter (ng*h/mL)] |
3480
(26)
|
5000
(45)
|
5870
(49)
|
6330
(NA)
|
| Title | Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8 |
|---|---|
| Description | Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination with Dexamethasone in Day 8 |
| Time Frame | Cycle 1 Day 8: Predose, 1-2, 3-4,6-8,24-30 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug in Part A and had evaluable PK data. |
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 5 | 8 | 12 | 2 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3050
(18)
|
4070
(92)
|
4640
(55)
|
8240
(NA)
|
| Title | Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations |
|---|---|
| Description | ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of participants achieving a CR or a CRi divided by the total number of participants randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm. |
| Time Frame | Baseline to Objective Disease Progression (Up To 12 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug in Part A. |
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 6 | 12 | 15 | 3 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR |
|---|---|
| Description | |
| Time Frame | Baseline to Objective Disease Progression (Up To 12 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. There were no participants enrolled in Phase 2 of the study. |
| Arm/Group Title | LY3039478 + Dexamethasone | Placebo + Dexamethasone |
|---|---|---|
| Arm/Group Description | LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Placebo administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 0 | 0 |
| Title | Phase 2: Number of Participants Who Achieve PR |
|---|---|
| Description | |
| Time Frame | Baseline to Objective Disease Progression (Up To 12 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. There were no participants enrolled in Phase 2 of the study. |
| Arm/Group Title | LY3039478 + Dexamethasone | Placebo + Dexamethasone |
|---|---|---|
| Arm/Group Description | LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Placebo administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 0 | 0 |
| Title | Phase 2: Duration of Remission (DoR) |
|---|---|
| Description | |
| Time Frame | Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. There were no participants enrolled in Phase 2 of the study. |
| Arm/Group Title | LY3039478 + Dexamethasone | Placebo + Dexamethasone |
|---|---|---|
| Arm/Group Description | LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Placebo administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 0 | 0 |
| Title | Phase 2:Relapse Free Survival (RFS) |
|---|---|
| Description | |
| Time Frame | Date of CR to Relapse or Death from any Cause (Approximately 1 Year) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. There were no participants enrolled in Phase 2 of the study. |
| Arm/Group Title | LY3039478 + Dexamethasone | Placebo + Dexamethasone |
|---|---|---|
| Arm/Group Description | LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Placebo administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 0 | 0 |
| Title | Phase 2: Event Free Survival (EFS) |
|---|---|
| Description | |
| Time Frame | Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. There were no participants enrolled in Phase 2 of the study. |
| Arm/Group Title | LY3039478 + Dexamethasone | Placebo + Dexamethasone |
|---|---|---|
| Arm/Group Description | LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Placebo administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 0 | 0 |
| Title | Phase 2: Overall Survival (OS) |
|---|---|
| Description | |
| Time Frame | Baseline to the Date of Death from Any Cause (Approximately 1.5 Years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. There were no participants enrolled in Phase 2 of the study. |
| Arm/Group Title | LY3039478 + Dexamethasone | Placebo + Dexamethasone |
|---|---|---|
| Arm/Group Description | LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Placebo administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 0 | 0 |
| Title | Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score |
|---|---|
| Description | |
| Time Frame | Baseline, End of Study (Approximately 1.5 Years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. There were no participants enrolled in Phase 2 of the study. |
| Arm/Group Title | LY3039478 + Dexamethasone | Placebo + Dexamethasone |
|---|---|---|
| Arm/Group Description | LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Placebo administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | Up To 16 Months | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone | ||||
| Arm/Group Description | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. | Part A: 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression | Part A: 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression | ||||
All Cause Mortality |
||||||||
| 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 8/12 (66.7%) | 12/15 (80%) | 2/3 (66.7%) | ||||
Serious Adverse Events |
||||||||
| 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 11/12 (91.7%) | 9/15 (60%) | 3/3 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Febrile neutropenia | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Colitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Diarrhoea | 1/6 (16.7%) | 2 | 2/12 (16.7%) | 3 | 2/15 (13.3%) | 4 | 1/3 (33.3%) | 5 |
| Gastric ulcer | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/6 (0%) | 0 | 2/12 (16.7%) | 3 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Ileus | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Intestinal obstruction | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Nausea | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 2 | 0/3 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Vomiting | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| General disorders | ||||||||
| Fatigue | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Non-cardiac chest pain | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Pain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Pyrexia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Infections and infestations | ||||||||
| Atypical pneumonia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Bacteraemia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Device related infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| H1n1 influenza | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Lung infection | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Neutropenic infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Perirectal abscess | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 2 |
| Pneumonia | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 2 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Sepsis | 0/6 (0%) | 0 | 1/12 (8.3%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Septic shock | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Upper respiratory tract infection | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Overdose | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Investigations | ||||||||
| Lipase increased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Weight decreased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/6 (0%) | 0 | 3/12 (25%) | 3 | 2/15 (13.3%) | 3 | 1/3 (33.3%) | 1 |
| Failure to thrive | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Hypokalaemia | 0/6 (0%) | 0 | 1/12 (8.3%) | 3 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Tumour lysis syndrome | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscular weakness | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Nasopharyngeal cancer | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Nervous system disorders | ||||||||
| Generalised tonic-clonic seizure | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Haemorrhage intracranial | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Syncope | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/6 (0%) | 0 | 1/12 (8.3%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Aspiration | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Dyspnoea | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hypoxia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Respiratory failure | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypotension | 1/6 (16.7%) | 1 | 3/12 (25%) | 3 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| 50 mg LY3039478 + Dexamethasone | 75 mg LY3039478 + Dexamethasone | 100 mg LY3039478 + Dexamethasone | 125 mg LY3039478 + Dexamethasone | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 12/12 (100%) | 15/15 (100%) | 3/3 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 3/6 (50%) | 4 | 2/12 (16.7%) | 3 | 3/15 (20%) | 4 | 1/3 (33.3%) | 1 |
| Febrile neutropenia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Immune thrombocytopenic purpura | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Increased tendency to bruise | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Leukocytosis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 2/15 (13.3%) | 4 | 0/3 (0%) | 0 |
| Thrombocytopenia | 1/6 (16.7%) | 2 | 1/12 (8.3%) | 1 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Bradycardia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 2 | 0/3 (0%) | 0 |
| Cardiac failure congestive | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Pericardial effusion | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Sinus bradycardia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Sinus tachycardia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Supraventricular tachycardia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Tachycardia | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 3/15 (20%) | 3 | 0/3 (0%) | 0 |
| Ventricular fibrillation | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Ventricular tachycardia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Ear pain | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hypoacusis | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Tinnitus | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Diabetes insipidus | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Eye disorders | ||||||||
| Exophthalmos | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Eye pain | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Ocular hyperaemia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Periorbital oedema | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Photophobia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Vision blurred | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Vitritis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Abdominal distension | 2/6 (33.3%) | 2 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Abdominal pain | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 3/15 (20%) | 3 | 0/3 (0%) | 0 |
| Abdominal pain upper | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 2/15 (13.3%) | 2 | 1/3 (33.3%) | 1 |
| Colitis | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Constipation | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 4/15 (26.7%) | 4 | 1/3 (33.3%) | 1 |
| Diarrhoea | 3/6 (50%) | 3 | 7/12 (58.3%) | 20 | 8/15 (53.3%) | 19 | 2/3 (66.7%) | 6 |
| Dry mouth | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 3/15 (20%) | 3 | 0/3 (0%) | 0 |
| Dyspepsia | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Dysphagia | 2/6 (33.3%) | 2 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Eructation | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Flatulence | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Gastric haemorrhage | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Gingival bleeding | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Haematemesis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Haematochezia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Haemorrhoids | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Ileus | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Lip dry | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Mouth haemorrhage | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Nausea | 1/6 (16.7%) | 1 | 5/12 (41.7%) | 8 | 5/15 (33.3%) | 6 | 3/3 (100%) | 8 |
| Oesophagitis | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Pancreatitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Proctalgia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Proctitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Rectal haemorrhage | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Stomatitis | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 3/15 (20%) | 3 | 0/3 (0%) | 0 |
| Toothache | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Vomiting | 2/6 (33.3%) | 2 | 3/12 (25%) | 4 | 8/15 (53.3%) | 8 | 3/3 (100%) | 9 |
| General disorders | ||||||||
| Asthenia | 0/6 (0%) | 0 | 3/12 (25%) | 5 | 3/15 (20%) | 3 | 0/3 (0%) | 0 |
| Chest pain | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Chills | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Complication associated with device | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Face oedema | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Fatigue | 0/6 (0%) | 0 | 3/12 (25%) | 3 | 6/15 (40%) | 10 | 2/3 (66.7%) | 8 |
| Malaise | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Mucosal inflammation | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Multiple organ dysfunction syndrome | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Non-cardiac chest pain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 2/15 (13.3%) | 2 | 1/3 (33.3%) | 1 |
| Oedema peripheral | 2/6 (33.3%) | 2 | 1/12 (8.3%) | 3 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Pyrexia | 2/6 (33.3%) | 2 | 3/12 (25%) | 4 | 4/15 (26.7%) | 4 | 1/3 (33.3%) | 1 |
| Hepatobiliary disorders | ||||||||
| Hepatomegaly | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Immune system disorders | ||||||||
| Hypersensitivity | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Infections and infestations | ||||||||
| Bacteraemia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Bronchitis | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Bronchopulmonary aspergillosis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Candida infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Cellulitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Clostridium difficile colitis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Clostridium difficile infection | 0/6 (0%) | 0 | 2/12 (16.7%) | 3 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Conjunctivitis | 1/6 (16.7%) | 2 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Corona virus infection | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Cytomegalovirus infection | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Dermatophytosis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Enterococcal infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Epstein-barr virus infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Folliculitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Gastroenteritis norovirus | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hordeolum | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Infective glossitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Influenza | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Lung infection | 1/6 (16.7%) | 2 | 0/12 (0%) | 0 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Mucosal infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Nasopharyngitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Oral candidiasis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pharyngitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pneumonia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pneumonia cytomegaloviral | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pneumonia fungal | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pseudomonas infection | 0/6 (0%) | 0 | 1/12 (8.3%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Rhinitis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Rhinovirus infection | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Sepsis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Septic encephalopathy | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Sinusitis | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Staphylococcal infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Tonsillitis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Upper respiratory tract infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Urinary tract infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Fall | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Muscle strain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Overdose | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 2/6 (33.3%) | 2 | 2/12 (16.7%) | 4 | 3/15 (20%) | 5 | 1/3 (33.3%) | 2 |
| Amylase increased | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 2 | 0/3 (0%) | 0 |
| Aspartate aminotransferase increased | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 6 | 4/15 (26.7%) | 8 | 1/3 (33.3%) | 3 |
| Blood bilirubin increased | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 2/15 (13.3%) | 4 | 0/3 (0%) | 0 |
| Blood creatinine increased | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Blood glucose increased | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Blood lactate dehydrogenase increased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 3 | 0/3 (0%) | 0 |
| Blood phosphorus increased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| C-reactive protein increased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 5 | 0/3 (0%) | 0 |
| Chest x-ray abnormal | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Gamma-glutamyltransferase increased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 2 | 1/3 (33.3%) | 5 |
| Immunoglobulins decreased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Lipase increased | 1/6 (16.7%) | 2 | 2/12 (16.7%) | 8 | 4/15 (26.7%) | 8 | 0/3 (0%) | 0 |
| Platelet count decreased | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 2/15 (13.3%) | 9 | 0/3 (0%) | 0 |
| Weight decreased | 1/6 (16.7%) | 2 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Weight increased | 0/6 (0%) | 0 | 1/12 (8.3%) | 3 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| White blood cell count decreased | 1/6 (16.7%) | 6 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 3 | 5/15 (33.3%) | 5 | 0/3 (0%) | 0 |
| Dehydration | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Fluid overload | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hyperglycaemia | 2/6 (33.3%) | 4 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hyperkalaemia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 2/15 (13.3%) | 3 | 0/3 (0%) | 0 |
| Hypernatraemia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 4 | 0/3 (0%) | 0 |
| Hyperphosphataemia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Hyperuricaemia | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hypoalbuminaemia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 1/3 (33.3%) | 1 |
| Hypocalcaemia | 0/6 (0%) | 0 | 1/12 (8.3%) | 2 | 5/15 (33.3%) | 7 | 0/3 (0%) | 0 |
| Hypokalaemia | 2/6 (33.3%) | 2 | 3/12 (25%) | 5 | 8/15 (53.3%) | 14 | 0/3 (0%) | 0 |
| Hypomagnesaemia | 2/6 (33.3%) | 2 | 2/12 (16.7%) | 8 | 2/15 (13.3%) | 3 | 0/3 (0%) | 0 |
| Hyponatraemia | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Hypophosphataemia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 4/15 (26.7%) | 4 | 1/3 (33.3%) | 5 |
| Hypoproteinaemia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hypouricaemia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Lactic acidosis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Malnutrition | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Tumour lysis syndrome | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/6 (0%) | 0 | 1/12 (8.3%) | 2 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Back pain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Bone pain | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Muscle spasms | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Muscular weakness | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Musculoskeletal pain | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Myalgia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pain in extremity | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Nervous system disorders | ||||||||
| Ageusia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Aphonia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Depressed level of consciousness | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Dizziness | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Dysgeusia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Headache | 1/6 (16.7%) | 2 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Lethargy | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Metabolic encephalopathy | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Seizure | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Syncope | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Psychiatric disorders | ||||||||
| Anxiety | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Depressed mood | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Depression | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Dysphoria | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Insomnia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 4/15 (26.7%) | 5 | 0/3 (0%) | 0 |
| Mental disorder | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 2/6 (33.3%) | 2 | 2/12 (16.7%) | 2 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Dysuria | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Urinary retention | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory failure | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Cough | 3/6 (50%) | 3 | 1/12 (8.3%) | 1 | 6/15 (40%) | 6 | 0/3 (0%) | 0 |
| Dysphonia | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Dyspnoea | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 2 | 3/15 (20%) | 3 | 0/3 (0%) | 0 |
| Epistaxis | 3/6 (50%) | 3 | 1/12 (8.3%) | 1 | 4/15 (26.7%) | 4 | 1/3 (33.3%) | 2 |
| Hiccups | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/3 (33.3%) | 1 |
| Hypoxia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Nasal congestion | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Oropharyngeal pain | 2/6 (33.3%) | 2 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pleural effusion | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 2/15 (13.3%) | 3 | 0/3 (0%) | 0 |
| Pneumonitis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Productive cough | 0/6 (0%) | 0 | 1/12 (8.3%) | 2 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pulmonary fibrosis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Pulmonary oedema | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Respiratory failure | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Rhinitis allergic | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Sinus congestion | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Tachypnoea | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Wheezing | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Dermatitis acneiform | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Dermatitis allergic | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Dry skin | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Ecchymosis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Erythema | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hand dermatitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Night sweats | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Pruritus | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Rash | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Rash maculo-papular | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 2 | 1/15 (6.7%) | 3 | 0/3 (0%) | 0 |
| Scab | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Skin ulcer | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Vascular disorders | ||||||||
| Flushing | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/3 (0%) | 0 |
| Hypertension | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
| Hypotension | 2/6 (33.3%) | 2 | 1/12 (8.3%) | 1 | 2/15 (13.3%) | 2 | 0/3 (0%) | 0 |
| Peripheral artery thrombosis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/3 (0%) | 0 |
Limitations/Caveats
There were no participants enrolled to Part B and Phase 2 of the study.
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 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02518113
Other Study ID Numbers:
- 14548
- I6F-MC-JJCB
- 2014-005024-10
First Posted:
Aug 7, 2015
Last Update Posted:
Sep 11, 2019
Last Verified:
Aug 1, 2019