Dose-Escalation Study of LY573636-sodium and Liposomal Doxorubicin in Patients With Advanced Solid Tumors
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01214668
Collaborator
(none)
31
5
1
37
6.2
0.2
Study Details
Study Description
Brief Summary
The goal of this study is to determine the dose of LY573636-sodium (hereafter referred to as LY573636) that can be administered safely in combination with liposomal doxorubicin in patients with advanced cancer who have failed a prior treatment.
The study consists of a dose escalation phase to the maximum tolerated dose (MTD) and a dose confirmation phase in patients with platinum resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have never been treated with doxorubicin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
31 participants
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b, Multicenter, Dose-Escalation Study of LY573636-sodium in Combination With Liposomal Doxorubicin in Patients With Advanced Solid Tumors
Study Start Date
:
Jan 1, 2009
Actual Primary Completion Date
:
Feb 1, 2012
Actual Study Completion Date
:
Feb 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY573636 + Liposomal Doxorubicin
|
Drug: LY573636-sodium
Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28-day cycle.
Participants may continue on study drug until disease progression, unacceptable toxicity, cumulative dose of 550 milligrams per square meter (mg/m²) of liposomal doxorubicin or doxorubicin is reached, or other withdrawal criterion is met.
Other Names:
Drug: Liposomal Doxorubicin
40 mg/m² on Day 1, given intravenously of each 28-day cycle
Participants may continue on study drug until disease progression, unacceptable toxicity, cumulative dose of 550 mg/m² of liposomal doxorubicin or doxorubicin is reached, or other withdrawal criterion are met.
|
Outcome Measures
Primary Outcome Measures
- Recommended Phase 2 Dose [Predose up to 28 days postdose in Cycle 1]
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which is corrected for the participant's predose albumin to identify the albumin-corrected exposure range of LY 573636 when combined with liposomal doxorubicin. MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) in the first 28-day cycle of treatment. DLT is an adverse event (AE) that is likely related to the study drug or combination and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity; Gr 3 nonhematologic toxicity (excluding controllable nausea/vomiting or diarrhea and alopecia); Gr 3 electrolyte toxicity that is not resolved with standard treatments. Those who enter the study with Gr 2 hepatic enzyme abnormalities, DLT for an isolated Gr 3 hepatic enzyme abnormality is determined by investigators; a DLT can be declared if a participant experiences increasing toxicity during treatment.
Secondary Outcome Measures
- Number of Participants With Clinically Significant Events [Baseline to study completion up to 18.49 months]
Clinically significant events are defined as serious adverse events (SAEs), regardless of causality, during the study including the 30-day follow-up period. A summary of SAEs and other nonserious adverse events is located in the Reported Adverse Event section. Death due to progressive disease was not considered as an SAE.
- Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 [Predose, 30 minutes (min), 2 hours (h), 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3]
- Number of Participants With Tumor Response [Baseline to measured progressive disease up to 4.7 months]
Number of participants with tumor response = number of participants with complete response (CR) + number of participants with partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in the sum of longest diameter of target lesions.
- Pharmacokinetics: Area Under the Curve of LY573636 Above the Albumin Corrected Threshold (AUCalb) [Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3]
LY573636 has been found to be highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) LY573636.
Other Outcome Measures
- Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment [From date of randomization until up to 30 days post study treatment discontinuation, assessed up to 4.7 months]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
You must have a histologically confirmed solid malignancy that is unresectable and/or metastatic which has progressed after receiving standard approved chemotherapy
-
You must have a solid malignancy for which an anthracycline-based regimen is felt to be a reasonable treatment option
-
You must have measurable disease or non-measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
-
You must have a serum albumin level greater than or equal to 3.0 grams/deciliter (g/dL) (30 g/L)
-
You must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
-
You must have tumor progression after receiving standard/approved chemotherapy
-
You must be reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures
-
Women must be sterile, post-menopausal or on a contraception and men must be sterile or on contraception
-
Your test results assessing the function of your blood, kidneys, liver, and heart are satisfactory
-
Ovarian patients in the confirmation phase must have failed to achieve at least a partial response to a first-line platinum-based therapy (platinum-refractory) or have progression in less than 6 months after a response to a first-line platinum-based therapy (platinum-resistant)
-
Ovarian patients in the confirmation phase must have measurable disease by RECIST
-
Ovarian patients in the confirmation phase must be liposomal doxorubicin or doxorubicin naive and not amendable to curative therapy
Exclusion Criteria:
-
You cannot have received other investigational drugs within the last 28 days
-
You cannot have other on-going serious illnesses including active bacterial, fugal, or viral infections
-
You cannot have current hematologic malignancies, acute or chronic leukemia, or brain metastasis
-
You cannot currently be receiving warfarin (Coumadin®) therapy
-
You cannot have known positive test results in human immunodeficiency, hepatitis B surface antigen or hepatitis C antibodies
-
You cannot have a history of cardiac disease or clinical evidence of congestive heart failure
-
Ovarian patients in the confirmation phase who have received 2 or more cytotoxic regimens for platinum-resistant disease
-
You cannot currently be receiving amiodarone, quinidine, propofol, and clozapine
-
If you are taking esomeprazole or pantoprazole you must be able to stop taking this medication within 72 hours before and after LY573636 administration
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Scottsdale | Arizona | United States | 85258 |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Encinitas | California | United States | 92024 |
| 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. | Oklahoma City | Oklahoma | United States | 73104 |
| 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. | Memphis | Tennessee | United States | 38119 |
| 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. | Seattle | Washington | United States | 98195 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 317-651-4559 Mon. - Fri. 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01214668
Other Study ID Numbers:
- 12887
- H8K-MC-JZAN
First Posted:
Oct 5, 2010
Last Update Posted:
Jan 4, 2019
Last Verified:
Dec 1, 2018
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The reasons for discontinuation listed in the participant flow are the reasons the participant discontinued treatment and a participant was considered to have "completed" the trial if they experienced progressive disease or an adverse event. |
| Arm/Group Title | LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox |
|---|---|---|---|---|---|---|
| Arm/Group Description | LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hour*micrograms per milliliter (h*µg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored). |
| Period Title: Overall Study | ||||||
| STARTED | 4 | 3 | 6 | 6 | 6 | 6 |
| Received at Least One Dose of Study Drug | 4 | 3 | 6 | 6 | 6 | 6 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 3 | 6 | 6 | 6 | 6 |
Baseline Characteristics
| Arm/Group Title | LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hour*micrograms per milliliter (h*μg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored). | Total of all reporting groups |
| Overall Participants | 4 | 3 | 6 | 6 | 6 | 6 | 31 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
57.39
(13.60)
|
51.54
(8.55)
|
64.65
(7.53)
|
58.57
(2.71)
|
52.24
(15.08)
|
57.82
(12.97)
|
57.54
(10.93)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
4
100%
|
2
66.7%
|
6
100%
|
5
83.3%
|
5
83.3%
|
6
100%
|
28
90.3%
|
| Male |
0
0%
|
1
33.3%
|
0
0%
|
1
16.7%
|
1
16.7%
|
0
0%
|
3
9.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
2
50%
|
1
33.3%
|
0
0%
|
1
16.7%
|
2
33.3%
|
0
0%
|
6
19.4%
|
| Not Hispanic or Latino |
2
50%
|
2
66.7%
|
6
100%
|
5
83.3%
|
4
66.7%
|
6
100%
|
25
80.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
16.7%
|
0
0%
|
2
6.5%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
3
75%
|
3
100%
|
5
83.3%
|
6
100%
|
5
83.3%
|
6
100%
|
28
90.3%
|
| More than one race |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||||||
| United States |
4
100%
|
3
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
31
100%
|
Outcome Measures
| Title | Recommended Phase 2 Dose |
|---|---|
| Description | Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which is corrected for the participant's predose albumin to identify the albumin-corrected exposure range of LY 573636 when combined with liposomal doxorubicin. MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) in the first 28-day cycle of treatment. DLT is an adverse event (AE) that is likely related to the study drug or combination and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity; Gr 3 nonhematologic toxicity (excluding controllable nausea/vomiting or diarrhea and alopecia); Gr 3 electrolyte toxicity that is not resolved with standard treatments. Those who enter the study with Gr 2 hepatic enzyme abnormalities, DLT for an isolated Gr 3 hepatic enzyme abnormality is determined by investigators; a DLT can be declared if a participant experiences increasing toxicity during treatment. |
| Time Frame | Predose up to 28 days postdose in Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of the study drug. |
| Arm/Group Title | LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox |
|---|---|---|---|---|---|---|
| Arm/Group Description | LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hour*micrograms per milliliter (h*µg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored). |
| Measure Participants | 4 | 3 | 6 | 6 | 6 | 6 |
| Number [micrograms per milliliter (μg/mL)] |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
| Title | Number of Participants With Clinically Significant Events |
|---|---|
| Description | Clinically significant events are defined as serious adverse events (SAEs), regardless of causality, during the study including the 30-day follow-up period. A summary of SAEs and other nonserious adverse events is located in the Reported Adverse Event section. Death due to progressive disease was not considered as an SAE. |
| Time Frame | Baseline to study completion up to 18.49 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of the study drug. |
| Arm/Group Title | LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox |
|---|---|---|---|---|---|---|
| Arm/Group Description | LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hour*micrograms per milliliter (h*µg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored). |
| Measure Participants | 4 | 3 | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
2
50%
|
0
0%
|
5
83.3%
|
3
50%
|
3
50%
|
3
50%
|
| Title | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 |
|---|---|
| Description | |
| Time Frame | Predose, 30 minutes (min), 2 hours (h), 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received the study drug and had sufficient pharmacokinetic (PK) data to estimate Cmax at the specified time points. |
| Arm/Group Title | LY573636 |
|---|---|
| Arm/Group Description | LY573636 dose was based on an albumin-corrected exposure (AUCalb) to target a specific exposure range. Intravenous dosing is done on Day 1 of a 28-day cycle. Data are pooled together from all treatment groups. |
| Measure Participants | 31 |
| Cycle 1 |
335.1
(13.9)
|
| Cycle 2 |
284.5
(15.9)
|
| Cycle 3 |
250.7
(25.2)
|
| Title | Number of Participants With Tumor Response |
|---|---|
| Description | Number of participants with tumor response = number of participants with complete response (CR) + number of participants with partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in the sum of longest diameter of target lesions. |
| Time Frame | Baseline to measured progressive disease up to 4.7 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of the study drug. |
| Arm/Group Title | LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox |
|---|---|---|---|---|---|---|
| Arm/Group Description | LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hour*micrograms per milliliter (h*µg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored). |
| Measure Participants | 4 | 3 | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
1
25%
|
0
0%
|
1
16.7%
|
3
50%
|
0
0%
|
2
33.3%
|
| Title | Pharmacokinetics: Area Under the Curve of LY573636 Above the Albumin Corrected Threshold (AUCalb) |
|---|---|
| Description | LY573636 has been found to be highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) LY573636. |
| Time Frame | Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received the study drug and had sufficient pharmacokinetic (PK) data to calculate AUCalb at the specified time points. |
| Arm/Group Title | LY573636 |
|---|---|
| Arm/Group Description | LY573636 dose was based on an albumin-corrected exposure (AUCalb) to target a specific exposure range. Intravenous dosing is done on Day 1 of a 28-day cycle. Data are pooled together from all treatment groups. |
| Measure Participants | 31 |
| Cycle 1 |
1081.0
(163.9)
|
| Cycle 2 |
413.7
(684.3)
|
| Cycle 3 |
228.4
(323.3)
|
| Title | Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment |
|---|---|
| Description | |
| Time Frame | From date of randomization until up to 30 days post study treatment discontinuation, assessed up to 4.7 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of the study drug. |
| Arm/Group Title | LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox |
|---|---|---|---|---|---|---|
| Arm/Group Description | LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hour*micrograms per milliliter (h*µg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored). |
| Measure Participants | 4 | 3 | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
Adverse Events
| Time Frame | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Deaths due to progressive disease are not considered adverse events and are reported in the Other Pre-Specified Outcome Measure for those who died within the 30-day post study treatment follow-up period. | |||||||||||
| Arm/Group Title | LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox | ||||||
| Arm/Group Description | LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase. | LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hour*micrograms per milliliter (h*µg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored). | ||||||
All Cause Mortality |
||||||||||||
| LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 0/3 (0%) | 5/6 (83.3%) | 3/6 (50%) | 3/6 (50%) | 3/6 (50%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Neutropenia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Thrombocytopenia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Cardiac disorders | ||||||||||||
| Cardiac arrest | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||
| Vertigo | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Constipation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Dysphagia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Impaired gastric emptying | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Intestinal obstruction | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Large intestinal obstruction | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Nausea | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Oesophagitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Small intestinal obstruction | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 |
| Stomatitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vomiting | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| General disorders | ||||||||||||
| Mucosal inflammation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||
| Dilatation intrahepatic duct acquired | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Immune system disorders | ||||||||||||
| Drug hypersensitivity | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Infections and infestations | ||||||||||||
| H1n1 influenza | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Postoperative wound infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Sepsis syndrome | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Wound infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Investigations | ||||||||||||
| Blood creatinine increased | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| White blood cell count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Dehydration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hypokalaemia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Muscular weakness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Nervous system disorders | ||||||||||||
| Subarachnoid haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Vocal cord paralysis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| Confusional state | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Asthma | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Pneumonia aspiration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Pneumonitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Exfoliative rash | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vascular disorders | ||||||||||||
| Hypotension | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| LY 300 μg/mL + Dox | LY 320 μg/mL + Dox | LY 340 μg/mL + Dox | LY 360 μg/mL + Dox | LY 380 μg/mL + Dox | LY Albumin and Day 15 PK Tailored + Dox | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 3/3 (100%) | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 2/4 (50%) | 5 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 3/6 (50%) | 3 |
| Leukopenia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Lymphopenia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Neutropenia | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 4/6 (66.7%) | 5 | 3/6 (50%) | 4 |
| Thrombocytopenia | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/6 (50%) | 4 | 1/6 (16.7%) | 1 |
| Cardiac disorders | ||||||||||||
| Cardiac failure congestive | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Palpitations | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Pericardial effusion | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Sinus tachycardia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Ear and labyrinth disorders | ||||||||||||
| Deafness | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Ear discomfort | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Ear pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Tinnitus | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Eye disorders | ||||||||||||
| Abnormal sensation in eye | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Eye irritation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Photopsia | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Scleral discolouration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Vision blurred | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 |
| Visual impairment | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Abdominal distension | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Abdominal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 |
| Abdominal pain upper | 1/4 (25%) | 1 | 2/3 (66.7%) | 2 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 3 |
| Anal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Constipation | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 |
| Diarrhoea | 2/4 (50%) | 3 | 1/3 (33.3%) | 1 | 5/6 (83.3%) | 5 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 2 | 2/6 (33.3%) | 2 |
| Dry mouth | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Duodenal ulcer | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Dyspepsia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Dysphagia | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Faeces hard | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Flatulence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Gastrointestinal pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Gingival bleeding | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Gingival pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Glossodynia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Haematochezia | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Intestinal obstruction | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 |
| Lip blister | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Lip ulceration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Mouth ulceration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Nausea | 1/4 (25%) | 2 | 3/3 (100%) | 3 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 3/6 (50%) | 4 |
| Odynophagia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Oesophagitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Oral pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| Proctalgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Rectal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Rectal ulcer | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Small intestinal obstruction | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Stomatitis | 2/4 (50%) | 6 | 3/3 (100%) | 3 | 2/6 (33.3%) | 2 | 4/6 (66.7%) | 4 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Tongue disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Tongue ulceration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vomiting | 2/4 (50%) | 3 | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 2/6 (33.3%) | 2 |
| General disorders | ||||||||||||
| Asthenia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Catheter site pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Catheter site swelling | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Chest pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Chills | 2/4 (50%) | 3 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Device occlusion | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Early satiety | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Face oedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Fatigue | 2/4 (50%) | 3 | 2/3 (66.7%) | 2 | 5/6 (83.3%) | 5 | 2/6 (33.3%) | 2 | 4/6 (66.7%) | 5 | 2/6 (33.3%) | 2 |
| Feeling abnormal | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Generalised oedema | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Infusion site pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Injection site haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Injection site pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Mucosal inflammation | 1/4 (25%) | 2 | 1/3 (33.3%) | 2 | 2/6 (33.3%) | 2 | 3/6 (50%) | 4 | 3/6 (50%) | 5 | 3/6 (50%) | 5 |
| Non-cardiac chest pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Oedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Oedema peripheral | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Pain | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Pyrexia | 4/4 (100%) | 5 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| Thrombosis in device | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||
| Gallbladder pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Bronchitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Candidiasis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Clostridial infection | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Escherichia infection | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Fungal infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Gastric infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Herpes zoster | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Hordeolum | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Lung infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Nasopharyngitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Oral candidiasis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Oral herpes | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Pneumonia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Rash pustular | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Sinusitis | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Urinary tract infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 3/6 (50%) | 4 | 4/6 (66.7%) | 4 |
| Injury, poisoning and procedural complications | ||||||||||||
| Contusion | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Facial bones fracture | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 |
| Fall | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 4 |
| Infusion related reaction | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Laceration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| Muscle strain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Nail injury | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Procedural pain | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Investigations | ||||||||||||
| Blood alkaline phosphatase increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Blood creatinine | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Blood creatinine increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Ejection fraction decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Haemoglobin decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| Neutrophil count decreased | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Weight decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/6 (66.7%) | 4 |
| Weight increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 1/4 (25%) | 1 | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 |
| Dehydration | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Hyperglycaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 5 | 1/6 (16.7%) | 1 |
| Hypoalbuminaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Hypokalaemia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 4/6 (66.7%) | 7 |
| Hypomagnesaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 |
| Hyponatraemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hypophosphataemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| Arthritis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Back pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Joint stiffness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Joint swelling | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Muscle spasms | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Muscle twitching | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Muscular weakness | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Musculoskeletal discomfort | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Musculoskeletal pain | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Myalgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 |
| Neck pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Pain in extremity | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Nervous system disorders | ||||||||||||
| Ataxia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Dizziness | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Dysgeusia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Headache | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 4/6 (66.7%) | 5 | 4/6 (66.7%) | 5 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 |
| Hypoaesthesia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Neuropathy peripheral | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Paraesthesia | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Sedation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Tremor | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Psychiatric disorders | ||||||||||||
| Anxiety | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Depression | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Insomnia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Libido decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| Costovertebral angle tenderness | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Dysuria | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 |
| Haematuria | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Hydronephrosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Hypertonic bladder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Nocturia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Pollakiuria | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Renal failure acute | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Urinary incontinence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Urinary retention | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Urine abnormality | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Reproductive system and breast disorders | ||||||||||||
| Genital rash | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Menstruation irregular | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Pelvic pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Perineal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Pruritus genital | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vaginal discharge | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vaginal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Vaginal odour | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Vulvovaginal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 3 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Dysphonia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Dyspnoea | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 |
| Epistaxis | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 |
| Nasal congestion | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Nasal dryness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Oropharyngeal pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 |
| Rhinalgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 |
| Sinus disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Sneezing | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Upper-airway cough syndrome | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Wheezing | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Acne | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Alopecia | 1/4 (25%) | 1 | 2/3 (66.7%) | 2 | 1/6 (16.7%) | 1 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 4/6 (66.7%) | 4 |
| Blister | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Cold sweat | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Dermatitis contact | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Dry skin | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 |
| Exfoliative rash | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Hyperhidrosis | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hyperkeratosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Nail discolouration | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Nail disorder | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Night sweats | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Onychomadesis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Pain of skin | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Palmar-plantar erythrodysaesthesia syndrome | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Pruritus | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Rash | 0/4 (0%) | 0 | 2/3 (66.7%) | 5 | 4/6 (66.7%) | 6 | 3/6 (50%) | 5 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Rash generalised | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Rash maculo-papular | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Skin discolouration | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 1/6 (16.7%) | 2 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Skin hyperpigmentation | 2/4 (50%) | 3 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Skin mass | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Surgical and medical procedures | ||||||||||||
| Contraceptive diaphragm | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vascular disorders | ||||||||||||
| Flushing | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hot flush | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hypertension | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hypotension | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Thrombosis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01214668
Other Study ID Numbers:
- 12887
- H8K-MC-JZAN
First Posted:
Oct 5, 2010
Last Update Posted:
Jan 4, 2019
Last Verified:
Dec 1, 2018