Phase 1/2a Study of BAL101553 as 48-hour Infusions in Patients With Advanced Solid Tumors or Recurrent Glioblastoma
Sponsor
Basilea Pharmaceutica (Industry)
Overall Status
Completed
CT.gov ID
NCT02895360
Collaborator
(none)
43
6
2
47.4
7.2
0.2
Study Details
Study Description
Brief Summary
Single-agent, open-label, multi-center sequential dose escalation and expansion study of BAL101553, administered as an intravenous (IV) infusion over 48 hours to adults with advanced or recurrent solid tumors or recurrent glioblastoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is the first study of prolonged intravenous infusion of BAL101553 (lisavanbulin). BAL101553 will be administered as an intravenous infusion over 48 hours, to adults with advanced or recurrent solid tumors or recurrent glioblastoma who have failed standard therapy, or for whom no effective standard therapy is available.
The primary goal of the study is to find the highest dose of BAL101553 that can safely be given to humans and to assess what side effects occur. The study will start by treating patients with a low dose. Once it has been shown that this low dose is well tolerated, new patients will be treated at higher dose levels ("dose escalation"). Once the highest, well tolerated dose is identified, up to 20 new patients with platinum-resistant/refractory ovarian cancer and up to 20 new patients with recurrent glioblastoma will be treated at that dose (this part is called "dose expansion") to further assess as secondary goal the tolerability and potential anticancer activity of BAL101553. A further secondary goal of this study is to assess the pharmacokinetics of BAL101553.
Study Design
Study Type:
Interventional
Actual Enrollment
:
43 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Phase 1/2a Study of BAL101553 Administered as Intravenous 48-hour Infusions in Adult Patients With Advanced Solid Tumors or Recurrent Glioblastoma
Actual Study Start Date
:
Aug 24, 2016
Actual Primary Completion Date
:
Aug 7, 2020
Actual Study Completion Date
:
Aug 7, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1 Fixed 3+3 dose escalation of BAL101553 in patients with advanced solid tumors |
Drug: BAL101553
BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; oral capsule daily for one week during Cycle 2 (study days 15-21)
|
| Experimental: Phase 2a BAL101553 at MTD in patients with platinum-resistant/refractory ovarian cancer or recurrent glioblastoma |
Drug: BAL101553 at MTD
BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; treatment with maximum tolerated dose (MTD)
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) of BAL101553 [28 day cycle]
First 28-day treatment cycle dose limiting toxicities (DLT) graded according to CTCAE in the MTD-determining population in Phase 1 based on the number of participants with adverse effects as measure of tolerability at various dose levels
Secondary Outcome Measures
- Safety and Tolerability of BAL101553 Treatment Based on Number of Patients With Related Treatment-emergent Adverse Events (TEAEs) in the Phase 1 and Phase 2a Safety Population at Various Dose Levels and Indication [TEAEs with onset on or after Day 1 of the study and until 28 days after the last dose]
TEAEs are defined as all events occurring after BAL101553 treatment begins, up to 28 days after last study drug administration according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
- AUC of BAL101553 and BAL27862 [0 to 168 hours post-dose at Day 1 of Cycle 1 and Cycle 2 in each cohort in Phase 1, 28-day cycles]
Pharmacokinetic parameter "Area under the plasma concentration versus time curve" AUC0-last (of BAL101553 and BAL27862 has been assessed after a 48-hour IV infusion. Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).
- Cmax of BAL101553 and BAL27862 [Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.]
Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of BAL101553 and BAL27862. Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).
- Tmax of BAL101553 and BAL27862 [Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.]
Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of BAL101553 and BAL27862
- Bioavailability of Daily Oral BAL101553 Measured by BAL27862 in Phase 1 [Relative oral bioavailability, calculated as dose-normalized AUC0-τ following oral administration on Cycle 2 Day 21 divided by dose normalized AUC0-∞ following IV administration on Cycle 1 Day 1 for each cohort.]
Ratio of AUCs of avanbulin after oral and IV administration (relative bioavailability) of BAL101553 (lisavanbulin) which is the prodrug of avanbulin (BAL27862)
- Anti-tumor Activity of BAL101553 by Best Response Rate Per RECIST / RANO Criteria [28 day cycles]
The objective response rate (ORR) was calculated using the efficacy evaluable populations (EEPs in Phase 2a) and the full analysis population (FAP in Phase 1 and Phase 2a) based on RECIST v1.1 guidelines (defines criteria for the radiological assessment in tumor response) for patients with solid tumors (excluding GBM (glioblastoma)) and RANO criteria (assessment Incorporating MRI and clinical factors) for patients with GBM. ORR = Rate of complete and partial responses
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age ≥ 18 years
-
Phase 1: Patients with either histologically or cytologically confirmed advanced or recurrent solid tumor, who failed standard therapy or for whom no effective standard therapy is available.
Phase 2a: Patients with platinum-resistant/refractory ovarian, fallopian tube or primary peritoneal cancer (high-grade serous, endometrioid, or carcinosarcoma histotypes) or glioblastoma in first relapse.
- Patients with solid tumors must have measurable disease according to Response Evaluation Criteria in Solid Tumors [RECIST] v1.1.
Patients with recurrent glioblastoma must have measurable disease defined by contrast-enhancing magnetic resonance imaging.
-
Life expectancy ≥ 12 weeks
-
Acceptable organ and marrow function at baseline (protocol defined laboratory parameters)
-
Patients with solid tumors must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 and patients with recurrent glioblastoma must have an ECOG performance status ≤ 2.
-
Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
- Patients with solid tumors who have received chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks prior to starting study drug or who have not recovered from side effects of prior therapies.
Patients with recurrent glioblastoma who have: received radiotherapy within 12 weeks, unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field, or there is histological confirmation of unequivocal tumor progression; received administration of prior antitumor chemotherapy within 4 weeks, or within 6 weeks for nitrosoureas; undergone surgical resection within 4 weeks or a stereotactic biopsy/core biopsy within 1 week prior to starting study drug, or have been treated previously with bevacizumab.
-
Patients who have had prior exposure to BAL101553.
-
Peripheral neuropathy ≥ CTCAE grade 2.
-
Uncontrolled intercurrent illness that would unduly increase the risk of toxicity or limit compliance with study requirements
-
Systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg at the screening visit.
-
Blood pressure (BP) combination treatment with more than two antihypertensive medications.
-
Women who are pregnant or breast-feeding. Men or women of reproductive potential who are not willing to apply effective birth control.
-
Other protocol-defined exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Oncology Institute of Southern Switzerland; Ospedale Regionale San Giovanni Bellinzona e Valli | Bellinzona | Switzerland | 6500 | |
| 2 | Inselspital Bern | Bern | Switzerland | 3010 | |
| 3 | Cantonal Hospital of Grisons, Department of Oncology/ Haematology | Chur | Switzerland | 7000 | |
| 4 | Centre Hospitalier Universitaire Vaudois | Lausanne | Switzerland | 1011 | |
| 5 | Cantonal Hospital of St. Gallen, Dep. Medical Oncology & Hematology | St. Gallen | Switzerland | 9007 | |
| 6 | UniversitaetsSpital Zürich | Zürich | Switzerland | 8091 |
Sponsors and Collaborators
- Basilea Pharmaceutica
Investigators
- Study Director: Thomas Kaindl, MD, Basilea Pharmaceutica
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Basilea Pharmaceutica
ClinicalTrials.gov Identifier:
NCT02895360
Other Study ID Numbers:
- CDI-CS-003
First Posted:
Sep 9, 2016
Last Update Posted:
Oct 11, 2021
Last Verified:
Sep 1, 2021
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase 1 - 30 mg/m² Cohort | Phase 1 - 45 mg/m² Cohort | Phase 1 - 70 mg/m² Cohort | Phase 1 - 90 mg/m² Cohort | Phase 2a - Ovarian Cancer Cohort | Phase 2a - Recurrent Glioblastoma Cohort |
|---|---|---|---|---|---|---|
| Arm/Group Description | BAL101553 30 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 30 mg/m². | BAL101553 45 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 45 mg/m². | BAL101553 70 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 70 mg/m². | BAL101553 90 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 90 mg/m². | BAL101553 at 70 mg/m² (MTD) BAL101553 as 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle |
| Period Title: Phase 1 - 30 mg/m² Cohort | ||||||
| STARTED | 4 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Phase 1 - 30 mg/m² Cohort | ||||||
| STARTED | 0 | 3 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 3 | 0 | 0 | 0 | 0 |
| Period Title: Phase 1 - 30 mg/m² Cohort | ||||||
| STARTED | 0 | 0 | 9 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 9 | 0 | 0 | 0 |
| Period Title: Phase 1 - 30 mg/m² Cohort | ||||||
| STARTED | 0 | 0 | 0 | 4 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 4 | 0 | 0 |
| Period Title: Phase 1 - 30 mg/m² Cohort | ||||||
| STARTED | 0 | 0 | 0 | 0 | 11 | 12 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 11 | 12 |
Baseline Characteristics
| Arm/Group Title | 30 mg/m² Cohort | 45 mg/m² Cohort | 70 mg/m² Cohort | 90 mg/m² Cohort | Phase 2a - Ovarian Cancer Cohort | Phase 2a - Recurrent Glioblastoma Cohort | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | BAL101553 30 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 30 mg/m². | BAL101553 45 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 45 mg/m². | BAL101553 70 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 70 mg/m². | BAL101553 90 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 90 mg/m². | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | Total of all reporting groups |
| Overall Participants | 4 | 3 | 9 | 4 | 11 | 12 | 43 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [Years] |
54.3
(3.30)
|
61.0
(0)
|
59.6
(10.53)
|
63.0
(7.26)
|
64.7
(8.78)
|
59.3
(7.45)
|
60.7
(8.25)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
2
50%
|
2
66.7%
|
6
66.7%
|
3
75%
|
11
100%
|
3
25%
|
27
62.8%
|
| Male |
2
50%
|
1
33.3%
|
3
33.3%
|
1
25%
|
0
0%
|
9
75%
|
16
37.2%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 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 |
4
100%
|
3
100%
|
9
100%
|
4
100%
|
11
100%
|
12
100%
|
43
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||||
| Switzerland |
4
100%
|
3
100%
|
9
100%
|
4
100%
|
11
100%
|
12
100%
|
43
100%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) of BAL101553 |
|---|---|
| Description | First 28-day treatment cycle dose limiting toxicities (DLT) graded according to CTCAE in the MTD-determining population in Phase 1 based on the number of participants with adverse effects as measure of tolerability at various dose levels |
| Time Frame | 28 day cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| MTD-determining population in Phase 1: All patients who meet the following minimum criteria during the first 28-day treatment cycle (Cycle 1) received at least one partial or complete dose of BAL101553 and has experienced a DLT; received all three doses of BAL101553 without experiencing a DLT (including the ability to initiate treatment Cycle 2), have been observed for ≥ 28 days following the first dose, and have been evaluated for safety. |
| Arm/Group Title | MTD-determining Population in Phase 1 |
|---|---|
| Arm/Group Description | All patients meeting the criteria of the MTD-determining population in Phase 1 during the first 28-day treatment cycle with intravenous BAL101553 at doses of 30, 45, 70 and 90 mg/m² |
| Measure Participants | 15 |
| Number [mg/m²] |
70
|
| Title | Safety and Tolerability of BAL101553 Treatment Based on Number of Patients With Related Treatment-emergent Adverse Events (TEAEs) in the Phase 1 and Phase 2a Safety Population at Various Dose Levels and Indication |
|---|---|
| Description | TEAEs are defined as all events occurring after BAL101553 treatment begins, up to 28 days after last study drug administration according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 |
| Time Frame | TEAEs with onset on or after Day 1 of the study and until 28 days after the last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who receive at least one full or partial dose of BAL101553 and had at least one post-baseline safety assessment is included in the safety analysis population. |
| Arm/Group Title | Phase 1 - 30 mg/m² Cohort | Phase 1 - 45 mg/m² Cohort | Phase 1 - 70 mg/m² Cohort | Phase 1 - 90 mg/m² Cohort | Phase 2a - Ovarian Cancer Cohort | Phase 2a - Recurrent Glioblastoma Cohort |
|---|---|---|---|---|---|---|
| Arm/Group Description | BAL101553 30 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 30 mg/m². | BAL101553 45 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 45 mg/m². | BAL101553 70 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 70 mg/m². | BAL101553 90 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 90 mg/m². | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle |
| Measure Participants | 4 | 3 | 9 | 4 | 11 | 12 |
| Patients with ≥1 related AE |
2
50%
|
2
66.7%
|
8
88.9%
|
3
75%
|
9
81.8%
|
4
33.3%
|
| Patients with CTCAE Grade 3/4 or severe related AE |
0
0%
|
0
0%
|
2
22.2%
|
2
50%
|
3
27.3%
|
1
8.3%
|
| Patients with ≥1 related serious AE |
0
0%
|
0
0%
|
2
22.2%
|
1
25%
|
0
0%
|
0
0%
|
| Title | AUC of BAL101553 and BAL27862 |
|---|---|
| Description | Pharmacokinetic parameter "Area under the plasma concentration versus time curve" AUC0-last (of BAL101553 and BAL27862 has been assessed after a 48-hour IV infusion. Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862). |
| Time Frame | 0 to 168 hours post-dose at Day 1 of Cycle 1 and Cycle 2 in each cohort in Phase 1, 28-day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set includes all patients who received at least one partial or complete dose of study drug and had at least one post-baseline PK assessment. |
| Arm/Group Title | 30 mg/m² Cycle 1 Day 1 | 30 mg/m² Cycle 2 Day 1 | 45 mg/m² Cycle 1 Day 1 | 45 mg/m² Cycle 2 Day 1 | 70 mg/m² Cycle 1 Day 1 | 70 mg/m² Cycle 2 Day 1 | 90 mg/m² Cycle 1 Day 1 | 90 mg/m² Cycle 2 Day 1 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | BAL101553 30 mg/m² Cohort Cycle 1 Day 1 | BAL101553 30 mg/m² Cohort Cycle 2 Day 1 | BAL101553 45 mg/m² Cohort Cycle 1 Day 1 | BAL101553 45 mg/m² Cohort Cycle 2 Day 1 | BAL101553 70 mg/m² Cohort Cycle 1 Day 1 | BAL101553 70 mg/m² Cohort Cycle 2 Day 1 | BAL101553 90 mg/m² Cohort Cycle 1 Day 1 | BAL101553 90 mg/m² Cohort Cycle 2 Day 1 |
| Measure Participants | 4 | 3 | 3 | 2 | 9 | 6 | 4 | 3 |
| BAL101553 |
1430
(43.9)
|
1310
(47.6)
|
2260
(43.9)
|
1890
(13.3)
|
3560
(45.9)
|
3550
(43.1)
|
4810
(74.0)
|
4150
(67.5)
|
| BAL27862 |
1730
(37.8)
|
2250
(58.2)
|
3440
(45.1)
|
3920
(57.7)
|
7720
(44.6)
|
6640
(49.3)
|
10400
(37.2)
|
10700
(39.3)
|
| Title | Cmax of BAL101553 and BAL27862 |
|---|---|
| Description | Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of BAL101553 and BAL27862. Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862). |
| Time Frame | Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set includes all patients who received at least one partial or complete dose of study drug and had at least one post-baseline PK assessment. |
| Arm/Group Title | 30 mg/m² Cycle 1 Day 1 | 30 mg/m² Cycle 2 Day 1 | 45 mg/m² Cycle 1 Day 1 | 45 mg/m² Cycle 2 Day 1 | 70 mg/m² Cycle 1 Day 1 | 70 mg/m² Cycle 2 Day 1 | 90 mg/m² Cycle 1 Day 1 | 90 mg/m² Cycle 2 Day 1 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | BAL101553 30 mg/m² Cohort Cycle 1 Day 1 | BAL101553 30 mg/m² Cohort Cycle 2 Day 1 | BAL101553 45 mg/m² Cohort Cycle 1 Day 1 | BAL101553 45 mg/m² Cohort Cycle 2 Day 1 | BAL101553 70 mg/m² Cohort Cycle 1 Day 1 | BAL101553 70 mg/m² Cohort Cycle 2 Day 1 | BAL101553 90 mg/m² Cohort Cycle 1 Day 1 | BAL101553 90 mg/m² Cohort Cycle 2 Day 1 |
| Measure Participants | 4 | 3 | 3 | 2 | 9 | 6 | 4 | 3 |
| BAL101553 |
43.0
(22.9)
|
44.2
(15.8)
|
69.3
(19.3)
|
60.9
(4.3)
|
119
(34.5)
|
111
(34.9)
|
174
(63.6)
|
198
(76.8)
|
| BAL27862 |
45.7
(30.2)
|
52.7
(45.8)
|
76.8
(18.6)
|
76.2
(43.1)
|
144
(25.7)
|
120
(41.2)
|
223
(44.7)
|
199
(40.4)
|
| Title | Tmax of BAL101553 and BAL27862 |
|---|---|
| Description | Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of BAL101553 and BAL27862 |
| Time Frame | Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set includes all patients who received at least one partial or complete dose of study drug and had at least one post-baseline PK assessment. |
| Arm/Group Title | 30 mg/m² Cycle 1 Day 1 | 30 mg/m² Cycle 2 Day 1 | 45 mg/m² Cycle 1 Day 1 | 45 mg/m² Cycle 2 Day 1 | 70 mg/m² Cycle 1 Day 1 | 70 mg/m² Cycle 2 Day 1 | 90 mg/m² Cycle 1 Day 1 | 90 mg/m² Cycle 2 Day 1 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | BAL101553 30 mg/m² Cohort Cycle 1 Day 1 | BAL101553 30 mg/m² Cohort Cycle 2 Day 1 | BAL101553 45 mg/m² Cohort Cycle 1 Day 1 | BAL101553 45 mg/m² Cohort Cycle 2 Day 1 | BAL101553 70 mg/m² Cohort Cycle 1 Day 1 | BAL101553 70 mg/m² Cohort Cycle 2 Day 1 | BAL101553 90 mg/m² Cohort Cycle 1 Day 1 | BAL101553 90 mg/m² Cohort Cycle 2 Day 1 |
| Measure Participants | 4 | 3 | 3 | 2 | 9 | 6 | 4 | 3 |
| BAL101553 |
39.0
|
30.0
|
29.0
|
27.1
|
4.00
|
1.56
|
2.53
|
1.17
|
| BAL27862 |
48.0
|
48.0
|
48.0
|
47.5
|
47.6
|
46.6
|
46.2
|
47.4
|
| Title | Bioavailability of Daily Oral BAL101553 Measured by BAL27862 in Phase 1 |
|---|---|
| Description | Ratio of AUCs of avanbulin after oral and IV administration (relative bioavailability) of BAL101553 (lisavanbulin) which is the prodrug of avanbulin (BAL27862) |
| Time Frame | Relative oral bioavailability, calculated as dose-normalized AUC0-τ following oral administration on Cycle 2 Day 21 divided by dose normalized AUC0-∞ following IV administration on Cycle 1 Day 1 for each cohort. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients with both Cycle 1 Day 1 AUC0-∞ and Cycle 2 Day 1 AUC0-τ evaluations |
| Arm/Group Title | 30 mg/m² | 45 mg/m² | 70 mg/m² | 90 mg/m² |
|---|---|---|---|---|
| Arm/Group Description | Patients with both Cycle 1 Day 1 AUC0-∞ and Cycle 2 Day 1 AUC0-τ evaluations | Patients with both Cycle 1 Day 1 AUC0-∞ and Cycle 2 Day 1 AUC0-τ evaluations | Patients with both Cycle 1 Day 1 AUC0-∞ and Cycle 2 Day 1 AUC0-τ evaluations | Patients with both Cycle 1 Day 1 AUC0-∞ and Cycle 2 Day 1 AUC0-τ evaluations |
| Measure Participants | 1 | 1 | 3 | 1 |
| Mean (Standard Deviation) [Ratio] |
1.11
(0)
|
1.32
(0)
|
0.796
(18.9)
|
0.893
(0)
|
| Title | Anti-tumor Activity of BAL101553 by Best Response Rate Per RECIST / RANO Criteria |
|---|---|
| Description | The objective response rate (ORR) was calculated using the efficacy evaluable populations (EEPs in Phase 2a) and the full analysis population (FAP in Phase 1 and Phase 2a) based on RECIST v1.1 guidelines (defines criteria for the radiological assessment in tumor response) for patients with solid tumors (excluding GBM (glioblastoma)) and RANO criteria (assessment Incorporating MRI and clinical factors) for patients with GBM. ORR = Rate of complete and partial responses |
| Time Frame | 28 day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAP: Patients who receive at least one partial or complete dose of BAL101553. EEP: Patients with progressive disease who completed at least Cycle 1 dosing and at least one on-study tumor assessment (clinical or radiological by RECIST v1.1 or RANO criteria) Patients with stable disease, partial or complete response, based on a radiological assessment by RECIST v1.1 or RANO criteria at the end of Cycle 2, with at least 4 doses of study drug in the first two cycles. |
| Arm/Group Title | Phase 1- in the FAP | Phase 2a - Patients With Ovarian Cancer in the FAP | Phase 2a - Patients With Ovarian Cancer in the EEP | Phase 2a - Patients With Recurrent Glioblastoma in the FAP | Phase 2a - Patients With Recurrent Glioblastoma in the EEP |
|---|---|---|---|---|---|
| Arm/Group Description | All dose cohorts (30 mg/m², 45 mg/m², 70 mg/m² and 90 mg/m²) of BAL101553 in patients with advanced solid tumors BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; oral capsule daily for one week during Cycle 2 | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle |
| Measure Participants | 20 | 11 | 8 | 12 | 8 |
| Complete response |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Stable disease |
3
75%
|
4
133.3%
|
3
33.3%
|
3
75%
|
2
18.2%
|
| Progressive disease |
15
375%
|
7
233.3%
|
5
55.6%
|
9
225%
|
6
54.5%
|
| Missing |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | First dose of study drug through 28 days after the administration of the last dose | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | TEAEs with onset on or after Day 1 of the study and until 28 days after the last dose. | |||||||||||
| Arm/Group Title | Phase 1 - 30 mg/m² Cohort | Phase 1 - 45 mg/m² Cohort | Phase 1 - 70 mg/m² Cohort | Phase 1 - 90 mg/m² Cohort | Phase 2a - Ovarian Cancer Cohort | Phase 2a - Recurrent Glioblastoma Cohort | ||||||
| Arm/Group Description | BAL101553 30 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 30 mg/m². | BAL101553 45 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 45 mg/m². | BAL101553 70 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 70 mg/m². | BAL101553 90 mg/m² intravenously over 48 hours on Days 1, 8 and 15 of each (at least one) 28-day treatment cycle. During cycle 2, oral BAL101553 was administered on study days 15-21. The oral dose was selected to match the weekly IV dose of 90 mg/m². | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | BAL101553 at 70 mg/m² (MTD) BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle | ||||||
All Cause Mortality |
||||||||||||
| Phase 1 - 30 mg/m² Cohort | Phase 1 - 45 mg/m² Cohort | Phase 1 - 70 mg/m² Cohort | Phase 1 - 90 mg/m² Cohort | Phase 2a - Ovarian Cancer Cohort | Phase 2a - Recurrent Glioblastoma Cohort | |||||||
| 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 | 0/4 (0%) | 0/3 (0%) | 3/9 (33.3%) | 0/4 (0%) | 3/11 (27.3%) | 2/12 (16.7%) | ||||||
Serious Adverse Events |
||||||||||||
| Phase 1 - 30 mg/m² Cohort | Phase 1 - 45 mg/m² Cohort | Phase 1 - 70 mg/m² Cohort | Phase 1 - 90 mg/m² Cohort | Phase 2a - Ovarian Cancer Cohort | Phase 2a - Recurrent Glioblastoma Cohort | |||||||
| 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 | 1/4 (25%) | 1/3 (33.3%) | 7/9 (77.8%) | 1/4 (25%) | 4/11 (36.4%) | 5/12 (41.7%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Anal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Ascites | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Nausea | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Vomiting | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| General disorders | ||||||||||||
| Asthenia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| General physical health deterioration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Pyrexia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Device related infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pneumonia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| Fall | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 2/12 (16.7%) | 2 |
| Femoral neck fracture | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Metastases to peritoneum | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Neoplasm progression | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Brain oedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Nervous system disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Neuropathy peripheral | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Partial seizures | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Seizure | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Somnolence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Product Issues | ||||||||||||
| Thrombosis in device | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 3 |
| Surgical and medical procedures | ||||||||||||
| Bladder neoplasm surgery | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Vascular disorders | ||||||||||||
| Haematoma | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypotension | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Vena cava thrombosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Phase 1 - 30 mg/m² Cohort | Phase 1 - 45 mg/m² Cohort | Phase 1 - 70 mg/m² Cohort | Phase 1 - 90 mg/m² Cohort | Phase 2a - Ovarian Cancer Cohort | Phase 2a - Recurrent Glioblastoma Cohort | |||||||
| 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%) | 9/9 (100%) | 4/4 (100%) | 11/11 (100%) | 11/12 (91.7%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 3/11 (27.3%) | 4 | 1/12 (8.3%) | 1 |
| Lymph node pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Cardiac disorders | ||||||||||||
| Palpitations | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Tachycardia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Ear and labyrinth disorders | ||||||||||||
| Ear pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Eye disorders | ||||||||||||
| Dry eye | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Vision blurred | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Gastrointestinal disorders | ||||||||||||
| Abdominal distension | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Abdominal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 4/9 (44.4%) | 4 | 2/4 (50%) | 4 | 6/11 (54.5%) | 9 | 0/12 (0%) | 0 |
| Abdominal pain upper | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 0/4 (0%) | 0 | 2/11 (18.2%) | 4 | 1/12 (8.3%) | 1 |
| Anal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Anal incontinence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Ascites | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Constipation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 4/9 (44.4%) | 5 | 2/4 (50%) | 2 | 6/11 (54.5%) | 7 | 2/12 (16.7%) | 2 |
| Diarrhoea | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/9 (22.2%) | 3 | 1/4 (25%) | 1 | 3/11 (27.3%) | 6 | 0/12 (0%) | 0 |
| Dry mouth | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Dysphagia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Flatulence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Ileus | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Nausea | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 2/4 (50%) | 2 | 1/11 (9.1%) | 4 | 4/12 (33.3%) | 4 |
| Proctalgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 2/11 (18.2%) | 2 | 0/12 (0%) | 0 |
| Proctitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Stomatitis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Subileus | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Vomiting | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 2/9 (22.2%) | 4 | 1/4 (25%) | 1 | 2/11 (18.2%) | 2 | 1/12 (8.3%) | 1 |
| General disorders | ||||||||||||
| Chest discomfort | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Chest pain | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Device related thrombosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Fatigue | 1/4 (25%) | 1 | 2/3 (66.7%) | 2 | 8/9 (88.9%) | 9 | 3/4 (75%) | 5 | 6/11 (54.5%) | 14 | 4/12 (33.3%) | 4 |
| Gait disturbance | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| General physical health deterioration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Influenza like illness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Localised oedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Non-cardiac chest pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Oedema peripheral | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 2/11 (18.2%) | 2 | 1/12 (8.3%) | 1 |
| Pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 2 | 1/11 (9.1%) | 2 | 0/12 (0%) | 0 |
| Pyrexia | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/9 (11.1%) | 1 | 1/4 (25%) | 3 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||||||||||
| Cystitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 2 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Lip infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Localised infection | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Nasopharyngitis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Oral herpes | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 1/12 (8.3%) | 2 |
| Pneumonia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Rhinitis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Skin infection | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Urinary tract infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||
| Fall | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Vascular access complication | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Wound | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Investigations | ||||||||||||
| Alanine aminotransferase increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Aspartate aminotransferase increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Blood creatinine increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Blood lactate dehydrogenase increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Creatinine renal clearance decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Lymphocyte count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 3 |
| Neutrophil count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Platelet count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Troponin T increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 2/12 (16.7%) | 2 |
| Weight decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Weight increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| White blood cell count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 4/9 (44.4%) | 7 | 3/4 (75%) | 3 | 6/11 (54.5%) | 6 | 1/12 (8.3%) | 1 |
| Dehydration | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Hyperglycaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 2 |
| Hyperkalaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Hyperuricaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Hypoglycaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 0/12 (0%) | 0 |
| Hypokalaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 2/4 (50%) | 4 | 3/11 (27.3%) | 4 | 1/12 (8.3%) | 1 |
| Hyponatraemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Back pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 2 | 0/4 (0%) | 0 | 4/11 (36.4%) | 5 | 0/12 (0%) | 0 |
| Bone pain | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Muscle spasms | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 3/11 (27.3%) | 3 | 2/12 (16.7%) | 3 |
| Muscle tightness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Muscular weakness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 2/12 (16.7%) | 4 |
| Musculoskeletal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Myalgia | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Pain in extremity | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 2 | 0/4 (0%) | 0 | 2/11 (18.2%) | 2 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Amnesia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Aphasia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Ataxia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Autonomic nervous system imbalance | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Balance disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Brain oedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Cognitive disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Disturbance in attention | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dizziness | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Dysaesthesia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dysarthria | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dysgeusia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Headache | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 3/12 (25%) | 5 |
| Hemianaesthesia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hemianopia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hemiplegia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Memory impairment | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Monoparesis | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Neuralgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Neurologic neglect syndrome | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Paraesthesia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 3/11 (27.3%) | 5 | 2/12 (16.7%) | 2 |
| Peripheral sensory neuropathy | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 7 | 0/12 (0%) | 0 |
| Presyncope | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Seizure | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Somnolence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| Agitation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Confusional state | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 1/11 (9.1%) | 2 | 1/12 (8.3%) | 1 |
| Depression | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Disorientation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hallucination | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 2/4 (50%) | 2 | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Insomnia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 2/4 (50%) | 3 | 4/11 (36.4%) | 7 | 0/12 (0%) | 0 |
| Mental disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Restlessness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 3 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| Haematuria | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Urinary incontinence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Urinary retention | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Reproductive system and breast disorders | ||||||||||||
| Breast pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 1/4 (25%) | 1 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Dyspnoea | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 3/9 (33.3%) | 4 | 0/4 (0%) | 0 | 4/11 (36.4%) | 4 | 1/12 (8.3%) | 1 |
| Epistaxis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Hiccups | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypoxia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Pulmonary embolism | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Alopecia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dry skin | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Eczema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Hyperhidrosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Pruritus | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Rash | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Vascular disorders | ||||||||||||
| Embolism | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Haematoma | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 2/12 (16.7%) | 2 |
| Hot flush | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/4 (0%) | 0 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Hypertension | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 3/11 (27.3%) | 6 | 0/12 (0%) | 0 |
| Hypotension | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/4 (25%) | 1 | 0/11 (0%) | 0 | 0/12 (0%) | 0 |
| Peripheral coldness | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 1/11 (9.1%) | 1 | 0/12 (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 | Thomas Kaindl, MD, Global Medical Director, Oncology |
|---|---|
| Organization | Basilea Pharmaceutica International Ltd. |
| Phone | +41615671505 |
| Thomas.Kaindl@basilea.com |
Responsible Party:
Basilea Pharmaceutica
ClinicalTrials.gov Identifier:
NCT02895360
Other Study ID Numbers:
- CDI-CS-003
First Posted:
Sep 9, 2016
Last Update Posted:
Oct 11, 2021
Last Verified:
Sep 1, 2021