A Study of SB-743921 in Non-Hodgkin Lymphoma and Hodgkin Lymphoma
Sponsor
Cytokinetics (Industry)
Overall Status
Completed
CT.gov ID
NCT00343564
Collaborator
(none)
68
8
2
51
8.5
0.2
Study Details
Study Description
Brief Summary
This study was an early-phase trial arranged into two phases. The Phase I portion was a dose-escalation study designed to assess the safety, tolerability and to identify the maximum tolerated dose of SB-743921 in patients with Non-Hodgkin Lymphoma and Hodgkin Lymphoma. Phase II was intended to assess the activity, safety and tolerability of SB-743921 in patients with Indolent and Aggressive Non-Hodgkin's Lymphomas exclusively. The Phase II portion of the study was not initiated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
68 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I-II Study to Determine the Safety, Pharmacokinetics and Potential Efficacy of Intravenous Administration of SB-743921 on Days 1 and 15 of a 28-Day Dosing Schedule in Patients With Non-Hodgkin Lymphoma and Hodgkin Lymphoma
Study Start Date
:
Apr 1, 2006
Actual Primary Completion Date
:
Jul 1, 2010
Actual Study Completion Date
:
Jul 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1 Dose Escalation Phase 1 dose escalation without and with GCSF support |
Drug: SB-743921
Phase 1: I.V. dose on Days 1 and 15 of a 28 day cycle starting at 2mg/m2 and increasing by 1 mg/m2 with possible prophylactic granulopoietic support until unacceptable toxicity develops.
|
| Experimental: Phase 2 Fixed Dose Phase 2 fixed dose based on Phase I findings stratified by NHL type |
Drug: SB-743921
Phase 2: I.V. dose and regimen will be determined based on Phase 1 findings.
|
Outcome Measures
Primary Outcome Measures
- Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. [28 days]
Maximum Tolerated Dose (MTD) was determined by testing increasing doses in cohorts with at least 3 patients each. MTD reflects the highest dose of drug that did not cause dose limiting toxicity (DLT).
Secondary Outcome Measures
- Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
- Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
- Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
- Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
- Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
- Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
- Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
- Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 [Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria: Phase 1: Patients with evaluable or measurable (by MRI or CT) Hodgkin's Disease or Non-Hodgkin's Lymphoma. Phase 2: Patients with Measurable Non-Hodgkin's Lymphomas (Indolent or Aggressive) only. - Patients with Indolent NHL must be relapsed or refractory to at least one prior line of therapy (CHOP, CVP, chlorambucil or fludaribine). Prior treatment with Rituximab is required. - Patients with Aggressive NHL refractory to (or relapsed from) at least one CHOP-based therapy who have had prior treatment with Rituximab and who are not candidates for high-dose chemotherapy or autologous stem cell transplantation. - ECOG performance status 0-2 - Autologous stem cell transplant recipients are eligible if 100 days have elapsed since procedure. Exclusion Criteria: Phase 1: History of prior radioimmunotherapy (Bexxar, Zevalin); These patients ARE permitted in the Phase 2 trial. - Current active malignancy besides NHL, except excised non-melanoma skin cancer, in-situ cervical or bladder cancer or early stage prostate cancer. - Patients with leptomeningeal of CNS lymphoma - Known allergy to and/or receipt of treatments contraindicated by administration of G-CSF - Patients with active Hepatitis B or C, or patients with HIV infection. - Pregnant or breast-feeding females. - Previous treatment with a KSP inhibitor
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 2 | Cornell University Medical Center | New York | New York | United States | 10021 |
| 3 | Memorial Sloan-Kettering Caner Center | New York | New York | United States | 10021 |
| 4 | Herbert Irving Comprehensive Cancer Center | New York | New York | United States | 10032 |
| 5 | University of North Carolina | Chapel Hill | North Carolina | United States | 27599 |
| 6 | Sarah Cannon Cancer Research Institute | Nashville | Tennessee | United States | 37203 |
| 7 | Russian Medical Academy of Postgraduate Education | Moscow | Russian Federation | 115478 | |
| 8 | St. Petersburg State PAVLOV Medical University | Saint Petersburg | Russian Federation | 197002 |
Sponsors and Collaborators
- Cytokinetics
Investigators
- Principal Investigator: Owen O'Connor, M.D./Ph.D., Columbia University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT00343564
Other Study ID Numbers:
- CY 2121
First Posted:
Jun 23, 2006
Last Update Posted:
Jan 13, 2020
Last Verified:
Jan 1, 2020
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 2 mg/m2 Without GCSF | 3 mg/m2 Without GCSF | 4 mg/m2 Without GCSF | 5 mg/m2 Without GCSF | 6 mg/m2 Without GCSF | 7 mg/m2 Without GCSF | 6 mg/m2 With GCSF | 7 mg/m2 With GCSF | 8 mg/m2 With GCSF | 9 mg/m2 With GCSF | 10 mg/m2 With GCSF |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase 1 dose escalation cohort 1 without GCSF support | Phase 1 dose escalation cohort 2 without GCSF support | Phase 1 dose escalation cohort 3 without GCSF support | Phase 1 dose escalation cohort 4 without GCSF support | Phase 1 dose escalation cohort 5 without GCSF support | Phase 1 dose escalation cohort 6 without GCSF support | Phase 1 dose escalation cohort 1 with GCSF support | Phase 1 dose escalation cohort 2 with GCSF support | Phase 1 dose escalation cohort 3 with GCSF support | Phase 1 dose escalation cohort 4 with GCSF support | Phase 1 dose escalation cohort 5 with GCSF support |
| Period Title: Overall Study | |||||||||||
| STARTED | 6 | 7 | 3 | 7 | 10 | 9 | 4 | 3 | 3 | 8 | 8 |
| COMPLETED | 6 | 7 | 3 | 7 | 10 | 9 | 4 | 3 | 3 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | 2 mg/m2 Without GCSF | 3 mg/m2 Without GCSF | 4 mg/m2 Without GCSF | 5 mg/m2 Without GCSF | 6 mg/m2 Without GCSF | 7 mg/m2 Without GCSF | 6 mg/m2 With GCSF | 7 mg/m2 With GCSF | 8 mg/m2 With GCSF | 9 mg/m2 With GCSF | 10 mg/m2 With GCSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase 1 dose escalation cohort 1 without GCSF support | Phase 1 dose escalation cohort 2 without GCSF support | Phase 1 dose escalation cohort 3 without GCSF support | Phase 1 dose escalation cohort 4 without GCSF support | Phase 1 dose escalation cohort 5 without GCSF support | Phase 1 dose escalation cohort 6 without GCSF support | Phase 1 dose escalation cohort 1 with GCSF support | Phase 1 dose escalation cohort 2 with GCSF support | Phase 1 dose escalation cohort 3 with GCSF support | Phase 1 dose escalation cohort 4 with GCSF support | Phase 1 dose escalation cohort 5 with GCSF support | Total of all reporting groups |
| Overall Participants | 6 | 7 | 3 | 7 | 10 | 9 | 4 | 3 | 3 | 8 | 8 | 68 |
| Age (Count of Participants) | ||||||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
| Between 18 and 65 years |
4
66.7%
|
7
100%
|
3
100%
|
3
42.9%
|
8
80%
|
6
66.7%
|
1
25%
|
2
66.7%
|
1
33.3%
|
4
50%
|
4
50%
|
43
63.2%
|
| >=65 years |
2
33.3%
|
0
0%
|
0
0%
|
4
57.1%
|
2
20%
|
2
22.2%
|
3
75%
|
1
33.3%
|
2
66.7%
|
4
50%
|
4
50%
|
24
35.3%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [years] |
62
(9)
|
43
(13)
|
33
(9)
|
57
(22)
|
48
(16)
|
42
(24)
|
69
(12)
|
63
(11)
|
63
(17)
|
48
(22)
|
56
(20)
|
52
(19)
|
| Sex: Female, Male (Count of Participants) | ||||||||||||
| Female |
4
66.7%
|
6
85.7%
|
1
33.3%
|
2
28.6%
|
4
40%
|
4
44.4%
|
2
50%
|
1
33.3%
|
1
33.3%
|
3
37.5%
|
1
12.5%
|
29
42.6%
|
| Male |
2
33.3%
|
1
14.3%
|
2
66.7%
|
5
71.4%
|
6
60%
|
5
55.6%
|
2
50%
|
2
66.7%
|
2
66.7%
|
5
62.5%
|
7
87.5%
|
39
57.4%
|
| Region of Enrollment (participants) [Number] | ||||||||||||
| United States |
6
100%
|
4
57.1%
|
1
33.3%
|
5
71.4%
|
7
70%
|
6
66.7%
|
4
100%
|
3
100%
|
2
66.7%
|
8
100%
|
7
87.5%
|
53
77.9%
|
| Russian Federation |
0
0%
|
3
42.9%
|
2
66.7%
|
2
28.6%
|
3
30%
|
3
33.3%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
1
12.5%
|
15
22.1%
|
Outcome Measures
| Title | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. |
|---|---|
| Description | Maximum Tolerated Dose (MTD) was determined by testing increasing doses in cohorts with at least 3 patients each. MTD reflects the highest dose of drug that did not cause dose limiting toxicity (DLT). |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population; all patients who received at least 1 dose of study drug were included in the intent-to-treat/safety populations. Efficacy evaluable; any patient who received both cycles of treatment. |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Maximum Tolerated Dose (MTD) was determined by testing increasing doses without GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses without GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses without GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses without GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses without GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses without GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses with GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses with GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses with GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses with GCSF support | Maximum Tolerated Dose (MTD) was determined by testing increasing doses with GCSF support |
| Measure Participants | 4 | 6 | 3 | 5 | 6 | 9 | 4 | 3 | 3 | 7 | 6 |
| Number [mg/m2] |
2
|
3
|
4
|
5
|
6
|
6
|
6
|
7
|
8
|
9
|
9
|
| Title | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 1 Cmax | Day 1 Cmax | Day 1 Cmax | Day 1 Cmax | Day 1 Cmax | Day 1 Cmax | Day 1 Cmax | Day 1 Cmax | Day 1 Cmax |
| Measure Participants | 5 | 6 | 3 | 6 | 13 | 12 | 3 | 7 | 6 |
| Mean (Standard Deviation) [ng/mL] |
172
(40.7)
|
348
(86.6)
|
357
(50.4)
|
514
(177)
|
600
(175)
|
689
(401)
|
1130
(189)
|
805
(501)
|
1180
(682)
|
| Title | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 1 Tmax | Day 1 Tmax | Day 1 Tmax | Day 1 Tmax | Day 1 Tmax | Day 1 Tmax | Day 1 Tmax | Day 1 Tmax | Day 1 Tmax |
| Measure Participants | 5 | 6 | 3 | 6 | 13 | 12 | 3 | 7 | 6 |
| Mean (Standard Deviation) [hr] |
1.20
(0.45)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.08
(0.28)
|
1.00
(0.43)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.17
(0.41)
|
| Title | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 1 Clast | Day 1 Clast | Day 1 Clast | Day 1 Clast | Day 1 Clast | Day 1 Clast | Day 1 Clast | Day 1 Clast | Day 1 Clast |
| Measure Participants | 5 | 6 | 3 | 6 | 13 | 12 | 3 | 7 | 6 |
| Mean (Standard Deviation) [ng/mL] |
36.9
(23.6)
|
61.6
(29.4)
|
59.5
(39.9)
|
79.1
(51.9)
|
133
(64.7)
|
103
(48.3)
|
144
(97.6)
|
122
(69.6)
|
245
(134)
|
| Title | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 1 AUClast | Day 1 AUClast | Day 1 AUClast | Day 1 AUClast | Day 1 AUClast | Day 1 AUClast | Day 1 AUClast | Day 1 AUClast | Day 1 AUClast |
| Measure Participants | 5 | 6 | 3 | 6 | 13 | 12 | 3 | 7 | 6 |
| Mean (Standard Deviation) [hr*ng/mL] |
1807
(1104)
|
2800
(988.6)
|
3269
(950.2)
|
3707
(1750)
|
5838
(2588)
|
5359
(3028)
|
6270
(2751)
|
5875
(3483)
|
11570
(6318)
|
| Title | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 15 Cmax | Day 15 Cmax | Day 15 Cmax | Day 15 Cmax | Day 15 Cmax | Day 15 Cmax | Day 15 Cmax | Day 15 Cmax | Day 15 Cmax |
| Measure Participants | 3 | 5 | 3 | 8 | 13 | 8 | 3 | 7 | 6 |
| Mean (Standard Deviation) [ng/mL] |
220
(51.2)
|
323
(120)
|
365
(45.2)
|
599
(383)
|
717
(278)
|
835
(442)
|
685
(163)
|
706
(344)
|
1430
(1620)
|
| Title | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 15 Tmax | Day 15 Tmax | Day 15 Tmax | Day 15 Tmax | Day 15 Tmax | Day 15 Tmax | Day 15 Tmax | Day 15 Tmax | Day 15 Tmax |
| Measure Participants | 3 | 5 | 3 | 8 | 13 | 8 | 3 | 7 | 6 |
| Mean (Standard Deviation) [hr] |
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
1.00
(0.00)
|
| Title | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 15 Clast | Day 15 Clast | Day 15 Clast | Day 15 Clast | Day 15 Clast | Day 15 Clast | Day 15 Clast | Day 15 Clast | Day 15 Clast |
| Measure Participants | 3 | 5 | 3 | 8 | 13 | 8 | 3 | 7 | 6 |
| Mean (Standard Deviation) [ng/mL] |
29.2
(11.8)
|
84.2
(60.8)
|
58.5
(29.8)
|
84.6
(47.9)
|
138
(103)
|
92.4
(50.5)
|
138
(94.9)
|
150
(105)
|
285
(290)
|
| Title | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Dose Escalation Cohort 5 6 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 6 7 mg/m2 (w/ and w/o GCSF) | Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Day 15 AUClast | Day 15 AUClast | Day 15 AUClast | Day 15 AUClast | Day 15 AUClast | Day 15 AUClast | Day 15 AUClast | Day 15 AUClast | Day 15 Clast |
| Measure Participants | 3 | 5 | 3 | 8 | 13 | 8 | 3 | 7 | 6 |
| Mean (Standard Deviation) [hr*ng/mL] |
1809
(464.1)
|
2363
(1187)
|
3380
(1456)
|
4105
(2190)
|
5869
(3417)
|
5116
(1728)
|
6041
(3010)
|
6178
(3630)
|
12590
(17850)
|
Adverse Events
| Time Frame | Adverse events were collected during the 28-day treatment period and at a 14-day follow up visit. | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Patients who received at least 1 dose of treatment were considered eligible for safety. | |||||||||||||||||||||
| Arm/Group Title | 2 mg/m2 Without GCSF | 3 mg/m2 Without GCSF | 4 mg/m2 Without GCSF | 5 mg/m2 Without GCSF | 6 mg/m2 Without GCSF | 7 mg/m2 Without GCSF | 6 mg/m2 With GCSF | 7 mg/m2 With GCSF | 8 mg/m2 With GCSF | 9 mg/m2 With GCSF | 10 mg/m2 With GCSF | |||||||||||
| Arm/Group Description | Phase 1 dose escalation cohort 1 without GCSF support | Phase 1 dose escalation cohort 2 without GCSF support | Phase 1 dose escalation cohort 3 without GCSF support | Phase 1 dose escalation cohort 4 without GCSF support | Phase 1 dose escalation cohort 5 without GCSF support | Phase 1 dose escalation cohort 6 without GCSF support | Phase 1 dose escalation cohort 1 with GCSF support | Phase 1 dose escalation cohort 2 with GCSF support | Phase 1 dose escalation cohort 3 with GCSF support | Phase 1 dose escalation cohort 4 with GCSF support | Phase 1 dose escalation cohort 5 with GCSF support | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
| 2 mg/m2 Without GCSF | 3 mg/m2 Without GCSF | 4 mg/m2 Without GCSF | 5 mg/m2 Without GCSF | 6 mg/m2 Without GCSF | 7 mg/m2 Without GCSF | 6 mg/m2 With GCSF | 7 mg/m2 With GCSF | 8 mg/m2 With GCSF | 9 mg/m2 With GCSF | 10 mg/m2 With GCSF | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | 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) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||||||
Serious Adverse Events |
||||||||||||||||||||||
| 2 mg/m2 Without GCSF | 3 mg/m2 Without GCSF | 4 mg/m2 Without GCSF | 5 mg/m2 Without GCSF | 6 mg/m2 Without GCSF | 7 mg/m2 Without GCSF | 6 mg/m2 With GCSF | 7 mg/m2 With GCSF | 8 mg/m2 With GCSF | 9 mg/m2 With GCSF | 10 mg/m2 With GCSF | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | 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 | 2/5 (40%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 3/10 (30%) | 1/9 (11.1%) | 1/4 (25%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 3/7 (42.9%) | |||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||
| Neutropenia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Anaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Haemolytic anaemia | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Cardiac disorders | ||||||||||||||||||||||
| Atrial fibrillation | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| General disorders | ||||||||||||||||||||||
| Heparin-induced thrombocytopenia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Sudden death | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||
| Hyperbilirubinaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Infections and infestations | ||||||||||||||||||||||
| Sepsis | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Clostridium infection | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Enterobacter bacteraemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Pneumococcal bacteraemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Pneumonia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Staphyloccal infection | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||
| Procedural hypotension | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||
| Dehydration | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||
| Malignant plural effusion | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||
| Haematuria | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Renal failure acute | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||
| 2 mg/m2 Without GCSF | 3 mg/m2 Without GCSF | 4 mg/m2 Without GCSF | 5 mg/m2 Without GCSF | 6 mg/m2 Without GCSF | 7 mg/m2 Without GCSF | 6 mg/m2 With GCSF | 7 mg/m2 With GCSF | 8 mg/m2 With GCSF | 9 mg/m2 With GCSF | 10 mg/m2 With GCSF | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | 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 | 5/5 (100%) | 6/6 (100%) | 3/3 (100%) | 6/6 (100%) | 10/10 (100%) | 8/9 (88.9%) | 4/4 (100%) | 3/3 (100%) | 3/3 (100%) | 7/7 (100%) | 7/7 (100%) | |||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||
| Anaemia | 1/5 (20%) | 1/6 (16.7%) | 0/3 (0%) | 1/6 (16.7%) | 4/10 (40%) | 2/9 (22.2%) | 2/4 (50%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 5/7 (71.4%) | |||||||||||
| Eosinophilia | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Febrile neutropenia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/7 (14.3%) | 0 |
| Leukocytosis | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 0 | 0/7 (0%) | 0 |
| Leukopenia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 0 | 1/6 (16.7%) | 0 | 2/10 (20%) | 0 | 0/9 (0%) | 0 | 2/4 (50%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 0 | 2/7 (28.6%) | 0 | 1/7 (14.3%) | 0 |
| Lymph node pain | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Lymphocytosis | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Lymphopenia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 0 | 1/7 (14.3%) | 0 |
| Neutropenia | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 1/3 (33.3%) | 0 | 5/6 (83.3%) | 0 | 5/10 (50%) | 0 | 7/9 (77.8%) | 0 | 3/4 (75%) | 0 | 1/3 (33.3%) | 0 | 3/3 (100%) | 0 | 4/7 (57.1%) | 0 | 5/7 (71.4%) | 0 |
| Pancytopenia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/7 (14.3%) | 0 |
| Thrombocytopenia | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 2/6 (33.3%) | 1/10 (10%) | 2/9 (22.2%) | 2/4 (50%) | 1/3 (33.3%) | 2/3 (66.7%) | 3/7 (42.9%) | 5/7 (71.4%) | |||||||||||
| Cardiac disorders | ||||||||||||||||||||||
| Atrial fibrillation | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Supraventricular extrasystoles | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Tachycardia | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||||
| Hypoacusis | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||
| Conjunctival haemorrhage | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Vision blurred | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Visual disturbance | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||
| Abdominal discomfort | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Abdominal distension | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 2/9 (22.2%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Abdominal pain | 0/5 (0%) | 0 | 2/6 (33.3%) | 0 | 1/3 (33.3%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 0 | 2/7 (28.6%) | 0 |
| Abdominal pain upper | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Constipation | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 0 | 1/6 (16.7%) | 0 | 1/10 (10%) | 0 | 1/9 (11.1%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 0 | 4/7 (57.1%) | 0 |
| Diarrhoea | 2/5 (40%) | 2/6 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Dry mouth | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/7 (14.3%) | 0 |
| Dyspepsia | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Dysphagia | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Gastritis | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Intestinal obstruction | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Lip ulceration | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Nausea | 1/5 (20%) | 2/6 (33.3%) | 0/3 (0%) | 0/6 (0%) | 3/10 (30%) | 1/9 (11.1%) | 1/4 (25%) | 1/3 (33.3%) | 0/3 (0%) | 2/7 (28.6%) | 2/7 (28.6%) | |||||||||||
| Stomach discomfort | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Stomatitis | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 0 | 1/7 (14.3%) | 0 |
| Vomiting | 1/5 (20%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 1/9 (11.1%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| General disorders | ||||||||||||||||||||||
| Asthenia | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/10 (20%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 0 | 0/7 (0%) | 0 |
| Chest discomfort | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Chest pain | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 0 | 0/7 (0%) | 0 |
| Chills | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Fatigue | 3/5 (60%) | 2/6 (33.3%) | 2/3 (66.7%) | 1/6 (16.7%) | 1/10 (10%) | 4/9 (44.4%) | 1/4 (25%) | 3/3 (100%) | 1/3 (33.3%) | 3/7 (42.9%) | 5/7 (71.4%) | |||||||||||
| Gait disturbance | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/7 (14.3%) | 0 |
| Malaise | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Oedema | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Oedema peripheral | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 0 | 1/6 (16.7%) | 0 | 1/10 (10%) | 0 | 1/9 (11.1%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 2/7 (28.6%) | 0 |
| Pain | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Performance status decreased | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/10 (20%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Peripheral coldness | 0/5 (0%) | 0 | 1/6 (16.7%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Pyrexia | 1/5 (20%) | 2/6 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 2/10 (20%) | 3/9 (33.3%) | 1/4 (25%) | 0/3 (0%) | 1/3 (33.3%) | 5/7 (71.4%) | 0/7 (0%) | |||||||||||
| Suprapubic pain | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Thirst | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||
| Hyperbilirubinaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Immune system disorders | ||||||||||||||||||||||
| Drug hypersensitivity | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Infections and infestations | ||||||||||||||||||||||
| Bronchitis | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Herpes simplex | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Herpes virus infection | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Herpes zoster | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Respiratory tract infection | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Respiratory tract infection viral | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Rhinitis | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Sinusitis | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Skin infection | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Tooth infection | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Upper respiratory tract infection | 0/5 (0%) | 2/6 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 1/7 (14.3%) | |||||||||||
| Urinary tract infection | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Vulvovaginal mycotic infection | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||
| Incision site complication | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Sunburn | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Tooth fracture | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Tracheal obstruction | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Investigations | ||||||||||||||||||||||
| Alanine aminotransferase increased | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/10 (10%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Aspartate aminotransferase increased | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/10 (10%) | 2/9 (22.2%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 0/7 (0%) | |||||||||||
| Blood alkaline phosphatase increased | 0/5 (0%) | 1/6 (16.7%) | 1/3 (33.3%) | 0/6 (0%) | 1/10 (10%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | |||||||||||
| Blood bicarbonate decreased | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Blood creatinine increased | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| C-reactive protein increased | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Electrocardiogram QT corrected interval prolonged | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Gamma-glutamyltransferase increased | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Urine colour abnormal | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Urine output decreased | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Weight decreased | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||
| Acidosis | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Anorexia | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 2/9 (22.2%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/7 (28.6%) | 3/7 (42.9%) | |||||||||||
| Cachexia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Dehydration | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hypercalcaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hyperglycaemia | 1/5 (20%) | 1/6 (16.7%) | 0/3 (0%) | 1/6 (16.7%) | 4/10 (40%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hyperkalaemia | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hypermagnesaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hypertriglyceridaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hyperuricaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 2/3 (66.7%) | 2/7 (28.6%) | 0/7 (0%) | |||||||||||
| Hypoalbuminaemia | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 2/10 (20%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 0/7 (0%) | |||||||||||
| Hypocalcaemia | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hypoglycaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hypokalaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Hypomagnesaemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hyponatraemia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 3/10 (30%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 1/7 (14.3%) | |||||||||||
| Hypophosphataemia | 0/5 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Metabolic acidosis | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Polydipsia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||
| Arthralgia | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Back pain | 0/5 (0%) | 2/6 (33.3%) | 0/3 (0%) | 0/6 (0%) | 2/10 (20%) | 0/9 (0%) | 0/4 (0%) | 2/3 (66.7%) | 0/3 (0%) | 0/7 (0%) | 2/7 (28.6%) | |||||||||||
| Bone pain | 1/5 (20%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 0/7 (0%) | |||||||||||
| Flank pain | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Limb discomfort | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Muscle spasms | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Musculoskeletal chest pain | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Myalgia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Neck pain | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Pain in extremity | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Sacral pain | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Shoulder pain | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||
| Malignant pleural effusion | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Nervous system disorders | ||||||||||||||||||||||
| Dizziness | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 2/7 (28.6%) | |||||||||||
| Dysarthria | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Dysgeusia | 2/5 (40%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Headache | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 2/9 (22.2%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hypoaesthesia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Neuropathy | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Neuropathy peripheral | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Paraesthesia | 2/5 (40%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Parosmia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Peripheral sensory neuropathy | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Sinus headache | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Somnolence | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Psychiatric disorders | ||||||||||||||||||||||
| Anxiety | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Depression | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Insomnia | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Libido decreased | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Mental status changes | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||
| Dysuria | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Neurogenic bladder | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Pollakiuria | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Polyuria | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Urinary tract obstruction | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||
| Erectile dysfunction | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Vaginal discharge | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||
| Atelectasis | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Cough | 1/5 (20%) | 2/6 (33.3%) | 0/3 (0%) | 0/6 (0%) | 2/10 (20%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 1/3 (33.3%) | 3/7 (42.9%) | 0/7 (0%) | |||||||||||
| Dysphonia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Dyspnoea | 1/5 (20%) | 1/6 (16.7%) | 0/3 (0%) | 1/6 (16.7%) | 1/10 (10%) | 2/9 (22.2%) | 1/4 (25%) | 2/3 (66.7%) | 1/3 (33.3%) | 3/7 (42.9%) | 0/7 (0%) | |||||||||||
| Dyspnoea exertional | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 2/7 (28.6%) | |||||||||||
| Epistaxis | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | |||||||||||
| Hiccups | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hypoxia | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Nasal congestion | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Pharyngolaryngeal pain | 0/5 (0%) | 1/6 (16.7%) | 1/3 (33.3%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Pleural effusion | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Productive cough | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | |||||||||||
| Respiratory failure | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 1/10 (10%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Rhinitis allergic | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Rhinorrhoea | 0/5 (0%) | 1/6 (16.7%) | 1/3 (33.3%) | 0/6 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Wheezing | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 2/9 (22.2%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||
| Alopecia | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Dry skin | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Hyperhidrosis | 0/5 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 2/9 (22.2%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Night sweats | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/7 (0%) | |||||||||||
| Palmar erythema | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Pruritus | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 2/9 (22.2%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Rash | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/9 (11.1%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Rash maculo-papular | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Skin ulcer | 0/5 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/7 (14.3%) | |||||||||||
| Urticaria | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Vascular disorders | ||||||||||||||||||||||
| Phlebitis | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Thrombosis | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
| Vein discolouration | 1/5 (20%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/10 (0%) | 0/9 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/7 (0%) | |||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor intends to publish the results of the trial in collaboration with the Investigators.
Results Point of Contact
| Name/Title | Project Manager |
|---|---|
| Organization | Cytokinetics,Inc. |
| Phone | 650-624-2918 |
Responsible Party:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT00343564
Other Study ID Numbers:
- CY 2121
First Posted:
Jun 23, 2006
Last Update Posted:
Jan 13, 2020
Last Verified:
Jan 1, 2020