FLORET: Febuxostat for Tumor Lysis Syndrome Prevention in Hematological Malignancies of Paediatric Patients and Adults
Sponsor
Menarini Group (Industry)
Overall Status
Terminated
CT.gov ID
NCT03605212
Collaborator
(none)
30
17
5
16.9
1.8
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the exposure of febuxostat in pediatric patients (≥6<18 years of age) and in adults suffering from hematological malignancies at intermediate to high risk of TLS and to compare the effect in terms of serum uric acid levels.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
In the FLORET study it is planned to enroll 3 groups of patients in order to receive oral administration (film-coated tablets) of two different dose levels of febuxostat: children (from 6 to less than 12 years of age) will receive two different dose levels respectively; adolescents (from 12 to less than 18 years of age) will receive 80 and 120 mg/day respectively and adults (equal or major than 18 years of age) will receive 120 mg/day. The two dose levels for children and adolescents groups were to be sequentially administered, whereas the groups that will receive the first dose levels will simultaneously start the treatment at the study beginning. The individual treatment duration will be of 7 to 9 days, according to chemotherapy duration, as per Investigator's judgement.
Study Design
Study Type:
Interventional
Actual Enrollment
:
30 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Open Label, Multi-centre, Parallel Group Study to Compare the Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of Febuxostat Between Pediatric Patients (≥6<18 Years of Age) and Adults
Actual Study Start Date
:
Feb 27, 2017
Actual Primary Completion Date
:
Jul 25, 2018
Actual Study Completion Date
:
Jul 25, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days |
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
|
| Experimental: Cohort 2 Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days |
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
|
| Experimental: Cohort 3 Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) |
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
|
| Experimental: Cohort 4 Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) |
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
|
| Active Comparator: Adults Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) |
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F) [7 days]
Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
- PK Parameter: Apparent Volume of Distribution (Vd/F) [7 days]
Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
- PK Parameter: Absorption Rate Constant (Ka) [7 days]
Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
- PK Parameter: Area Under Curve (AUC) [7 days]
AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
- PK Parameter: Maximum Plasma Concentration (Cmax) [7 days]
Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
- PK Parameter: Tmax [7 days]
Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Secondary Outcome Measures
- Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA) [8 days]
Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8)
- Assessment of Laboratory Tumor Lysis Syndrome (LTLS) [7 days]
Assessment of LTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). LTLS is diagnosed if levels of 2 or more values of uric acid, potassium, phosphate or calcium are more than or less than normal at presentation or if they change by at least 25% from baseline.
- Assessment of Clinical Tumor Lysis Syndrome (CTLS) [7 days]
Assessment of CTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). CTLS is present when LTLS is accompanied by at least one of the following significant clinical complications: increased creatinine level ≥ 1.5 upper limit of normal, cardiac arrhythmia/sudden death or seizure.
- Assessment of Treatment Emergent Signs and Symptoms (TESS) [Estimated maximum time frame: 27 days]
Assessment of incidence, severity (through Mild/Moderate/Severe scale), seriousness and treatment-causality of TESS from Screening Visit to End of Study Visit. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. An adverse event was considered as TESS if it occured for the first time or if it worsened in terms of seriousness or severity after first study drug intake.
- Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS) [Estimated maximum time frame: 27 days]
Number of participants affected by TESS from Screening Visit to End of Study Visit.
- Performance Status (PS) Evaluation [Estimated maximum time frame: 27 days]
Quality of life was to be assessed by PS evaluation from Screening Visit to End of Study Visit. The Karnofsky Performance Status (KPS) scale was to be used for patients aged 16 years and older; the Lansky Play Performance Status (LPS) scale was to be used for patients aged less than 16 years. Both scales range from scores of 0 to 100 points at intervals of 10 where 0 points represent the worst outcome (KPS: 0 = death; LPS: 0 = unresponsive) and 100 points the best (KPS: 100 = normal, no complaints, no evidence of disease; LPS: 100 = fully active).
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
male and female children of 6 to less than 12 years of age, adolescents of 12 to less than 18 years of age and adults from 18 years:
-
scheduled for first cytotoxic chemotherapy cycle because of hematologic malignancies
-
and at intermediate or high risk of TLS
-
and with no access to rasburicase
Exclusion Criteria:
-
patients with contraindications as per febuxostat summary of product characteristics
-
patients with severe renal insufficiency
-
patients with severe hepatic insufficiency
-
patients with diagnosis of Laboratory TLS (LTLS) or Clinical TLS (CTLS)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Tsaritsa Yoanna | Sofia | Bulgaria | 1527 | |
| 2 | Semmelweis Egyetem (paediatric) | Budapest | Hungary | 1083 | |
| 3 | Semmelweis Egyetem | Budapest | Hungary | 1085 | |
| 4 | Debreceni Egyetem Klinikai Központ | Debrecen | Hungary | 4032 | |
| 5 | SOC Oncologia Medica A - Centro di Riferimento Oncologico | Aviano | Pordenone | Italy | 33081 |
| 6 | Policlinico S. Orsola Malpighi | Bologna | Italy | 40138 | |
| 7 | A.O.U.C. Azienda Ospedaliero - Universitaria Careggi | Firenze | Italy | 50134 | |
| 8 | Azienda Ospedaliero Universitaria Meyer | Firenze | Italy | 50139 | |
| 9 | Istituto G Gaslini Ospedale Pediatrico IRCCS | Genova | Italy | 16147 | |
| 10 | Azienda Ospedaliero-Universitaria Pisana | Pisa | Italy | 56126 | |
| 11 | IRCCS Ospedale Pediatrico Bambino Gesù | Rome | Italy | 00165 | |
| 12 | Ospedale Infantile Regina Margherita | Torino | Italy | 10126 | |
| 13 | Azienda Ospedaliera Universitaria Integrata di Verona | Verona | Italy | 37126 | |
| 14 | Hospital de San Pedro de Alcantara | Caceres | Spain | 10002 | |
| 15 | Hospital General Universitario Gregorio Maranon | Madrid | Spain | 28007 | |
| 16 | Hospital Universitario La Paz | Madrid | Spain | 28046 | |
| 17 | Hospital Universitari i Politècnic La Fe | Valencia | Spain | 46026 |
Sponsors and Collaborators
- Menarini Group
Investigators
- Study Chair: Franco Locatelli, Prof, MD, IRCCS Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio, 4, 00165 Rome, IT
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Menarini Group
ClinicalTrials.gov Identifier:
NCT03605212
Other Study ID Numbers:
- FLO-02
- 2016-001445-61
First Posted:
Jul 30, 2018
Last Update Posted:
Jun 3, 2021
Last Verified:
Jan 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Menarini Group
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The first patient was screened and enrolled on 27 Feb 2017. The last patient completed the study on 16 Jul 2018. The study was conducted at 17 sites in 4 European countries. |
|---|---|
| Pre-assignment Detail | A total of 31 patients was screened, of whom 30 were enrolled and 28 completed the study regularly. Two enrolled patients were withdrawn from study drug treatment. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Period Title: Baseline Period | |||||
| STARTED | 3 | 0 | 3 | 0 | 24 |
| COMPLETED | 3 | 0 | 3 | 0 | 24 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
| Period Title: Baseline Period | |||||
| STARTED | 3 | 0 | 3 | 0 | 24 |
| COMPLETED | 2 | 0 | 3 | 0 | 23 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Total of all reporting groups |
| Overall Participants | 3 | 0 | 3 | 0 | 24 | 30 |
| Age (Count of Participants) | ||||||
| <=18 years |
3
100%
|
0
NaN
|
3
100%
|
0
NaN
|
0
0%
|
6
20%
|
| Between 18 and 65 years |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
14
58.3%
|
14
46.7%
|
| >=65 years |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
10
41.7%
|
10
33.3%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
7.33
(1.528)
|
14.00
(1.000)
|
60.21
(15.376)
|
50.30
(24.419)
|
||
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
1
33.3%
|
0
NaN
|
2
66.7%
|
0
NaN
|
11
45.8%
|
14
46.7%
|
| Male |
2
66.7%
|
0
NaN
|
1
33.3%
|
0
NaN
|
13
54.2%
|
16
53.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
NaN
|
1
33.3%
|
0
NaN
|
0
0%
|
1
3.3%
|
| Not Hispanic or Latino |
3
100%
|
0
NaN
|
2
66.7%
|
0
NaN
|
24
100%
|
29
96.7%
|
| Unknown or Not Reported |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
| White |
3
100%
|
0
NaN
|
2
66.7%
|
0
NaN
|
23
95.8%
|
28
93.3%
|
| More than one race |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
NaN
|
1
33.3%
|
0
NaN
|
1
4.2%
|
2
6.7%
|
| Region of Enrollment (participants) [Number] | ||||||
| Hungary |
0
0%
|
0
NaN
|
8
266.7%
|
8
Infinity
|
||
| Italy |
3
100%
|
3
Infinity
|
5
166.7%
|
11
Infinity
|
||
| Bulgaria |
0
0%
|
0
NaN
|
0
0%
|
0
NaN
|
||
| Spain |
0
0%
|
0
NaN
|
11
366.7%
|
11
Infinity
|
||
| Weight (kg) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [kg] |
26.13
(2.043)
|
60.47
(19.747)
|
75.60
(15.469)
|
68.92
(21.369)
|
||
Outcome Measures
| Title | Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F) |
|---|---|
| Description | Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8) |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | PK Parameter: Apparent Volume of Distribution (Vd/F) |
|---|---|
| Description | Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8) |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | PK Parameter: Absorption Rate Constant (Ka) |
|---|---|
| Description | Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8) |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | PK Parameter: Area Under Curve (AUC) |
|---|---|
| Description | AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8) |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | PK Parameter: Maximum Plasma Concentration (Cmax) |
|---|---|
| Description | Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8) |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | PK Parameter: Tmax |
|---|---|
| Description | Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8) |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA) |
|---|---|
| Description | Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8) |
| Time Frame | 8 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | Assessment of Laboratory Tumor Lysis Syndrome (LTLS) |
|---|---|
| Description | Assessment of LTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). LTLS is diagnosed if levels of 2 or more values of uric acid, potassium, phosphate or calcium are more than or less than normal at presentation or if they change by at least 25% from baseline. |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | Assessment of Clinical Tumor Lysis Syndrome (CTLS) |
|---|---|
| Description | Assessment of CTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). CTLS is present when LTLS is accompanied by at least one of the following significant clinical complications: increased creatinine level ≥ 1.5 upper limit of normal, cardiac arrhythmia/sudden death or seizure. |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | Assessment of Treatment Emergent Signs and Symptoms (TESS) |
|---|---|
| Description | Assessment of incidence, severity (through Mild/Moderate/Severe scale), seriousness and treatment-causality of TESS from Screening Visit to End of Study Visit. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. An adverse event was considered as TESS if it occured for the first time or if it worsened in terms of seriousness or severity after first study drug intake. |
| Time Frame | Estimated maximum time frame: 27 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 3 | 0 | 3 | 0 | 24 |
| TESS |
50
|
21
|
70
|
||
| TESS grade >/=3 |
11
|
2
|
20
|
||
| Serious TESS |
1
|
0
|
7
|
||
| Related TESS |
4
|
0
|
0
|
||
| Related TESS grade >/=3 |
2
|
0
|
0
|
||
| Related TESS/Drug Withdrawn |
2
|
0
|
0
|
| Title | Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS) |
|---|---|
| Description | Number of participants affected by TESS from Screening Visit to End of Study Visit. |
| Time Frame | Estimated maximum time frame: 27 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 3 | 0 | 3 | 0 | 24 |
| Number [participants] |
3
100%
|
3
Infinity
|
20
666.7%
|
| Title | Performance Status (PS) Evaluation |
|---|---|
| Description | Quality of life was to be assessed by PS evaluation from Screening Visit to End of Study Visit. The Karnofsky Performance Status (KPS) scale was to be used for patients aged 16 years and older; the Lansky Play Performance Status (LPS) scale was to be used for patients aged less than 16 years. Both scales range from scores of 0 to 100 points at intervals of 10 where 0 points represent the worst outcome (KPS: 0 = death; LPS: 0 = unresponsive) and 100 points the best (KPS: 100 = normal, no complaints, no evidence of disease; LPS: 100 = fully active). |
| Time Frame | Estimated maximum time frame: 27 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults |
|---|---|---|---|---|---|
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | Adverse events were collected over the entire duration of a patient's study participation, i.e. approximately 3 weeks. In addition, if after the end of the study the Investigator became aware of any AEs or follow-up in AEs already recorded, this information could be recorded in the eCRF until it was available. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Events were collected during Screening, i.e. after ICF signature until DAY 1, Visit 1 before first IMP intake and specifically Treatment Emergent Signs and Symptoms (TESSs) occurring from first IMP intake at Visit 1, DAY 1 until Visit 10, DAY 14. | |||||||||
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults | |||||
| Arm/Group Description | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Febuxostat: Intervention is orally administered to patients in this arm. | |||||
All Cause Mortality |
||||||||||
| Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 0/0 (NaN) | 0/3 (0%) | 0/0 (NaN) | 0/24 (0%) | |||||
Serious Adverse Events |
||||||||||
| Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 0/0 (NaN) | 0/3 (0%) | 0/0 (NaN) | 5/24 (20.8%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Febrile neutropenia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Proctitis | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| General disorders | ||||||||||
| Mucosal inflammation | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Infections and infestations | ||||||||||
| Septioc shock | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Staphylococcal infection | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Investigations | ||||||||||
| Enterobacter test positiv | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Adults | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 0/0 (NaN) | 3/3 (100%) | 0/0 (NaN) | 20/24 (83.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 2/3 (66.7%) | 2 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 4/24 (16.7%) | 4 |
| Lymphopenia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Neutropenia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 3/24 (12.5%) | 3 |
| Thrombocytopenia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 2/24 (8.3%) | 2 |
| Cardiac disorders | ||||||||||
| Arrhythmia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Extrasystoles | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 2/3 (66.7%) | 2 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 4/24 (16.7%) | 4 |
| Abdominal pain upper | 1/3 (33.3%) | 2 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Abdominal rigidity | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Anorectal discomfort | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Aphthous ulcer | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Constipation | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 3/3 (100%) | 3 | 0/0 (NaN) | 0 | 4/24 (16.7%) | 5 |
| Diarrhoea | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 4/24 (16.7%) | 5 |
| Dyspepsia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Faeces soft | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Gingival swelling | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hematemesis | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hematochezia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Lip pain | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Nausea | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Vomiting | 2/3 (66.7%) | 4 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 2/24 (8.3%) | 2 |
| General disorders | ||||||||||
| Asthenia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Chest pain | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Facial pain | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Inflammation | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Malaise | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Mucosal inflammation | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 2/24 (8.3%) | 2 |
| Oedema peripheral | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Pain | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Pyrexia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 3/24 (12.5%) | 3 |
| Infections and infestations | ||||||||||
| Oral herpes | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Investigations | ||||||||||
| ALT increased | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| AST increased | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| BP increased | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Blood triglycerides increased | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Gamma-glutamyltransferase | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hemoglobin decreased | 1/3 (33.3%) | 2 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Neutrophil count decreased | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Platelet count decreased | 1/3 (33.3%) | 2 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| White blood cell (WBC) count decreased | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 2/24 (8.3%) | 2 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Fluid retention | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 2/24 (8.3%) | 2 |
| Hyperglycaemia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 2/3 (66.7%) | 2 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Hyperkalaemia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hyperphosphataemia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hypo HDL cholesterolaemia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hypocalcaemia | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Hypokalaemia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 2/24 (8.3%) | 2 |
| Limb discomfort | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Muscoskeletal pain | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Pain in extremity | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Temporomandibular joint syndrome | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Dizziness | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Headache | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 2 | 0/0 (NaN) | 0 | 4/24 (16.7%) | 4 |
| Language disorder | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Paraesthesia | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Psychiatric disorders | ||||||||||
| Depression | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hallucination | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Bronchospasm | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Cough | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Epistaxis | 2/3 (66.7%) | 3 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Hiccups | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Wheezing | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Cold sweat | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Erythema | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Rash | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Skin discolouration | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Vascular disorders | ||||||||||
| Hot flush | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/3 (33.3%) | 1 | 0/0 (NaN) | 0 | 0/24 (0%) | 0 |
| Hypotension | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
| Thrombophlebitis | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 1/24 (4.2%) | 1 |
Limitations/Caveats
Data for all outcome measures were not collected due to the paucity of data in the minor patient population and in agreement with EMA with the exceptions of the secondary outcome Assessment of Treatment Emergent Signs and Symptoms (TESS).
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Prior to submitting the results of this study for publication or presentation, the Investigator will allow the sponsor at least 60 days time to review and comment upon the publication manuscript. It is agreed, that the results of the study will not be submitted for presentation, abstract, poster exhibition, or publication by the investigator until the sponsor has reviewed/commented and agreed to any publication.
Results Point of Contact
| Name/Title | Angela Capriati, MD PhD - Corporate Director Clinical Sciences |
|---|---|
| Organization | Menarini Group |
| Phone | +39 055 5680 ext 9990 |
| acapriati@menarini-ricerche.it |
Responsible Party:
Menarini Group
ClinicalTrials.gov Identifier:
NCT03605212
Other Study ID Numbers:
- FLO-02
- 2016-001445-61
First Posted:
Jul 30, 2018
Last Update Posted:
Jun 3, 2021
Last Verified:
Jan 1, 2019