Open Label Treatment Extension Study With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT01587040
Collaborator
(none)
61
21
4
70.1
2.9
0
Study Details
Study Description
Brief Summary
Primary Objective:
The purpose of this study was to determine the long term safety and tolerability of SAR245408 and SAR245409 as a monotherapy or as part of a combination regimen in participants who were benefiting from treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
The duration of the study for an individual participant included:
-
Baseline assessments: within 7 days prior to the first dose of investigational medicinal product (IMP).
-
Study treatment period(s):
Participants started study treatment at the beginning of the initiation or extension periods based on the length of prior therapy with SAR245408 or SAR245409
-
if <2 cycles, started with initiation period; Participant must have had completed all the visits in the initiation period before moving to the extension period.
-
if >=2 cycles, started with extension period; duration of extension period was unlimited.
-
Participants who took a SAR245408 or SAR245409 daily dose higher than their established dose of SAR245408 or SAR245409, respectively, in the parental study entered the study on Day 1 of the initiation period.
-
Participants who had dose interrupted in the parental study but fulfilled parental protocol criteria to restart IMP treatment entered the treatment-extension study on Day 1 of the initiation period.
-
Participants who fulfilled the parental study criteria for IMP treatment continuation but had ongoing Grade 2 adverse events (AEs) entered the treatment-extension study on Day 1 of the initiation period.
Participants continued to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 or SAR245409 were available to them outside of the clinical trial.
- Follow-up assessments: 23 to 37 days after the last dose of IMP.
Study Design
Study Type:
Interventional
Actual Enrollment
:
61 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
International, Multicenter, Open-label, Treatment-extension Study for Subjects Who Completed a Phase 1 or Phase 2 Parental Study to Continue Receiving Treatment With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen
Actual Study Start Date
:
Jul 20, 2012
Actual Primary Completion Date
:
May 23, 2018
Actual Study Completion Date
:
May 23, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SAR245408: Monotherapy Participants received SAR245408 400 milligrams (mg) once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). |
Drug: SAR245408
Pharmaceutical form: capsule or tablet Route of administration: oral
|
| Experimental: SAR245408: Combination Regimen Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab). |
Drug: SAR245408
Pharmaceutical form: capsule or tablet Route of administration: oral
|
| Experimental: SAR245409: Monotherapy Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). |
Drug: SAR245409
Pharmaceutical form: capsule or tablet Route of administration: oral
|
| Experimental: SAR245409: Combination Regimen Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab). |
Drug: SAR245409
Pharmaceutical form: capsule or tablet Route of administration: oral
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)]
Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. Serious adverse event (SAE): any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial/prolonged in-patient hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAEs: AEs that developed/worsened/became serious during on-treatment period (time from IMP until 30 days after last dose of any IMP). Any TEAE included participants with both SAE & non-SAEs. TEAE included participants with any treatment-emergent SAE (TESAE). TEAEs that led to death, dose reduction and/or delay, discontinuation & AEs related to treatment were reported. Grades (3=severe, 4=life-threatening/disabling) represents severity of AEs.
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters [From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)]
Hematological parameters assessed were anemia, neutropenia and thrombocytopenia. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Biochemical Parameters [From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)]
Biochemical parameters assessed were hyperglycemia, aspartate aminotransferase (ASAT) increased, alanine aminotransferase (ALAT) increased, hyperbilirubinemia, hypocalcemia, creatinine increased. Parameters were assessed as per the NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria :
I 01. Males or females enrolled in Phase 1 or Phase 2 studies of SAR245408 or SAR245409 as monotherapy or in combination with other regimens who had completed data collection for the primary endpoint(s) of the parental study or who were being treated beyond the parental study cut-off and meet all the criteria to continue to be treated per the parental protocol.
I 02. All sexually active participants (male and female) must agreed to continue to use accepted methods of barrier contraception (i.e., condoms) during the course of the study and for 3 months after discontinuation of study treatment. For women of childbearing potential and for men who could father a child, a second method of contraception in addition to a barrier method is recommended. Hormonal contraception should be avoided in participants taking SAR245408 due to possible drug-drug interaction.
I 03. Female participants of childbearing potential must had a negative pregnancy test at baseline. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had any evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to other causes, including prior chemotherapy, anti-estrogens, or ovarian suppression.
Exclusion criteria:
E 01. The participant discontinued the parental study due to toxicity. E 02. Ongoing Grade 3 or higher Adverse Event (AE). E 03. Ongoing Serious Adverse Event (SAE). E 04. Participants with ongoing dose interruption for any reason unless the participant fulfilled the criteria in the parental protocol for restarting IMP. In such case participant started the treatment-extension study on Day 1 of the initiation period.
E 05. The participant had any of the following laboratory values ≥ Common Terminology of Adverse Events (CTCAE) Grade 3
-
Absolute neutrophil count (ANC),
-
Platelet count,
-
Hemoglobin,
-
Bilirubin,
-
Serum creatinine or calculated creatinine clearance,
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
-
Fasting plasma glucose (FPG),
-
Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT).
E 06. The participant had a baseline corrected QT interval (QTc) >481 millisecond (msec) or if a participant has had a QTc interval increase of ≥ 60 msec from parental protocol baseline to an absolute value of > 470 msec.
E 07. The participant had a known allergy or hypersensitivity to components of the study treatment formulation(s).
E 08. The participant was pregnant or breastfeeding.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 840010 | Birmingham | Alabama | United States | 35205 |
| 2 | Investigational Site Number 840009 | Los Angeles | California | United States | 90024 |
| 3 | Investigational Site Number 840008 | Los Angeles | California | United States | 90033 |
| 4 | Investigational Site Number 840022 | Denver | Colorado | United States | 80262 |
| 5 | Investigational Site Number 840104 | Fort Myers | Florida | United States | 33919 |
| 6 | Investigational Site Number 840006 | Augusta | Georgia | United States | 30912 |
| 7 | Investigational Site Number 840004 | Boston | Massachusetts | United States | 02115 |
| 8 | Investigational Site Number 840021 | Saint Louis | Missouri | United States | 63110 |
| 9 | Investigational Site Number 840002 | New Brunswick | New Jersey | United States | 08903 |
| 10 | Investigational Site Number 840020 | Canton | Ohio | United States | 44718 |
| 11 | Investigational Site Number 840015 | Columbus | Ohio | United States | 43210 |
| 12 | Investigational Site Number 840017 | Philadelphia | Pennsylvania | United States | 19111 |
| 13 | Investigational Site Number 840007 | Nashville | Tennessee | United States | 37232 |
| 14 | Investigational Site Number 840003 | Dallas | Texas | United States | 75230 |
| 15 | Investigational Site Number 840005 | San Antonio | Texas | United States | 78229 |
| 16 | Investigational Site Number 840018 | Morgantown | West Virginia | United States | 26506 |
| 17 | Investigational Site Number 056001 | Leuven | Belgium | 3000 | |
| 18 | Investigational Site Number 250004 | Montpellier | France | 34295 | |
| 19 | Investigational Site Number 250003 | Pierre Benite Cedex | France | 69495 | |
| 20 | Investigational Site Number 250005 | Rouen Cedex | France | 76038 | |
| 21 | Investigational Site Number 724001 | Barcelona | Spain | 08035 |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT01587040
Other Study ID Numbers:
- TED12414
- 2011-006140-78
- U1111-1124-1403
First Posted:
Apr 27, 2012
Last Update Posted:
Apr 19, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 21 centers in 4 countries between 20 July 2012 and 23 May 2018. Participants who received SAR245408/SAR245409 (IMP) in parental studies (TED12471 [NCT01596270], ARD11437 [NCT01082068], TED12863 [NCT01943838]) were included in study. A total of 67 participants were screened and 61 participants were enrolled in this study. |
|---|---|
| Pre-assignment Detail | Participants who received IMP for <2 cycles in parental study, and participants who took a daily dose of IMP higher than their established dose entered treatment-extension study on Day 1 of initiation period; participants who received IMP >=2 cycles in parental study entered treatment-extension study on Day 1 of extension period. |
| Arm/Group Title | SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen |
|---|---|---|---|---|
| Arm/Group Description | Participants received SAR245408 400 milligrams (mg) once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). | Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab). | Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). | Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab). |
| Period Title: Overall Study | ||||
| STARTED | 17 | 3 | 37 | 4 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 17 | 3 | 37 | 4 |
Baseline Characteristics
| Arm/Group Title | SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received SAR245408 400 mg once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). | Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab). | Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). | Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab). | Total of all reporting groups |
| Overall Participants | 17 | 3 | 37 | 4 | 61 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
61.6
(13.1)
|
53.7
(2.1)
|
62.4
(12.0)
|
50.0
(15.8)
|
61.0
(12.5)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
12
70.6%
|
3
100%
|
16
43.2%
|
0
0%
|
31
50.8%
|
| Male |
5
29.4%
|
0
0%
|
21
56.8%
|
4
100%
|
30
49.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
1
33.3%
|
2
5.4%
|
0
0%
|
3
4.9%
|
| Not Hispanic or Latino |
17
100%
|
2
66.7%
|
35
94.6%
|
4
100%
|
58
95.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
1.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
17.6%
|
0
0%
|
5
13.5%
|
0
0%
|
8
13.1%
|
| White |
14
82.4%
|
2
66.7%
|
31
83.8%
|
4
100%
|
51
83.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
2.7%
|
0
0%
|
1
1.6%
|
Outcome Measures
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
|---|---|
| Description | Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. Serious adverse event (SAE): any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial/prolonged in-patient hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAEs: AEs that developed/worsened/became serious during on-treatment period (time from IMP until 30 days after last dose of any IMP). Any TEAE included participants with both SAE & non-SAEs. TEAE included participants with any treatment-emergent SAE (TESAE). TEAEs that led to death, dose reduction and/or delay, discontinuation & AEs related to treatment were reported. Grades (3=severe, 4=life-threatening/disabling) represents severity of AEs. |
| Time Frame | From Baseline up to 30 days after the last dose (maximum exposure: 1959 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population that included all participants who took at least 1 dose of study drug during the study. |
| Arm/Group Title | SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen |
|---|---|---|---|---|
| Arm/Group Description | Participants received SAR245408 400 mg once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). | Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab). | Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). | Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab). |
| Measure Participants | 17 | 3 | 37 | 4 |
| Any TEAE |
16
94.1%
|
3
100%
|
35
94.6%
|
3
75%
|
| Any Grade 3-4 TEAEs |
12
70.6%
|
2
66.7%
|
19
51.4%
|
1
25%
|
| Any related TEAEs |
12
70.6%
|
3
100%
|
23
62.2%
|
2
50%
|
| Any Grade 3-4 related TEAE |
3
17.6%
|
0
0%
|
11
29.7%
|
0
0%
|
| Any Serious TEAE |
9
52.9%
|
1
33.3%
|
10
27%
|
0
0%
|
| Any Grade 3-4 TESAE |
9
52.9%
|
1
33.3%
|
9
24.3%
|
0
0%
|
| Any related TESAE |
2
11.8%
|
0
0%
|
1
2.7%
|
0
0%
|
| Any Grade 3-4 related TESAE |
2
11.8%
|
0
0%
|
0
0%
|
0
0%
|
| Any TEAE leading to death |
0
0%
|
0
0%
|
3
8.1%
|
0
0%
|
| Any TEAE leading to permanent discontinuation |
1
5.9%
|
1
33.3%
|
8
21.6%
|
0
0%
|
| Any TEAE leading to dose reduction |
3
17.6%
|
1
33.3%
|
9
24.3%
|
1
25%
|
| Any TEAE leading to dose delay or interruption |
6
35.3%
|
2
66.7%
|
16
43.2%
|
0
0%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters |
|---|---|
| Description | Hematological parameters assessed were anemia, neutropenia and thrombocytopenia. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. |
| Time Frame | From Baseline up to 30 days after the last dose (maximum exposure: 1959 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. Here, "Overall number of participants analyzed" = participants with available data for this outcome measure. |
| Arm/Group Title | SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen |
|---|---|---|---|---|
| Arm/Group Description | Participants received SAR245408 400 mg once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). | Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab). | Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). | Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab). |
| Measure Participants | 16 | 3 | 36 | 4 |
| Anemia: All grades |
13
76.5%
|
1
33.3%
|
23
62.2%
|
1
25%
|
| Anemia: Grade 1 |
6
35.3%
|
1
33.3%
|
18
48.6%
|
1
25%
|
| Anemia: Grade 2 |
3
17.6%
|
0
0%
|
2
5.4%
|
0
0%
|
| Anemia: Grade 3 |
4
23.5%
|
0
0%
|
3
8.1%
|
0
0%
|
| Anemia: Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neutropenia: All grades |
7
41.2%
|
0
0%
|
10
27%
|
1
25%
|
| Neutropenia: Grade 1 |
2
11.8%
|
0
0%
|
5
13.5%
|
1
25%
|
| Neutropenia: Grade 2 |
2
11.8%
|
0
0%
|
1
2.7%
|
0
0%
|
| Neutropenia: Grade 3 |
2
11.8%
|
0
0%
|
2
5.4%
|
0
0%
|
| Neutropenia: Grade 4 |
1
5.9%
|
0
0%
|
2
5.4%
|
0
0%
|
| Thrombocytopenia: All grades |
8
47.1%
|
0
0%
|
20
54.1%
|
3
75%
|
| Thrombocytopenia: Grade 1 |
5
29.4%
|
0
0%
|
17
45.9%
|
3
75%
|
| Thrombocytopenia: Grade 2 |
0
0%
|
0
0%
|
2
5.4%
|
0
0%
|
| Thrombocytopenia: Grade 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Thrombocytopenia: Grade 4 |
3
17.6%
|
0
0%
|
1
2.7%
|
0
0%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Biochemical Parameters |
|---|---|
| Description | Biochemical parameters assessed were hyperglycemia, aspartate aminotransferase (ASAT) increased, alanine aminotransferase (ALAT) increased, hyperbilirubinemia, hypocalcemia, creatinine increased. Parameters were assessed as per the NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. |
| Time Frame | From Baseline up to 30 days after the last dose (maximum exposure: 1959 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. Here, "number analyzed"= participants with available data for specified category. |
| Arm/Group Title | SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen |
|---|---|---|---|---|
| Arm/Group Description | Participants received SAR245408 400 mg once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). | Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab). | Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). | Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab). |
| Measure Participants | 17 | 3 | 37 | 4 |
| Hyperglycemia: All Grades |
13
76.5%
|
3
100%
|
25
67.6%
|
1
25%
|
| Hyperglycemia: Grade 1 |
11
64.7%
|
2
66.7%
|
19
51.4%
|
1
25%
|
| Hyperglycemia: Grade 2 |
0
0%
|
1
33.3%
|
6
16.2%
|
0
0%
|
| Hyperglycemia: Grade 3 |
2
11.8%
|
0
0%
|
0
0%
|
0
0%
|
| Hyperglycemia: Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ASAT Increased: All Grades |
7
41.2%
|
2
66.7%
|
20
54.1%
|
1
25%
|
| ASAT Increased: Grade 1 |
6
35.3%
|
1
33.3%
|
16
43.2%
|
1
25%
|
| ASAT Increased: Grade 2 |
1
5.9%
|
1
33.3%
|
2
5.4%
|
0
0%
|
| ASAT Increased: Grade 3 |
0
0%
|
0
0%
|
2
5.4%
|
0
0%
|
| ASAT Increased: Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALAT Increased: All Grades |
5
29.4%
|
2
66.7%
|
12
32.4%
|
0
0%
|
| ALAT Increased: Grade 1 |
4
23.5%
|
1
33.3%
|
8
21.6%
|
0
0%
|
| ALAT Increased: Grade 2 |
1
5.9%
|
1
33.3%
|
1
2.7%
|
0
0%
|
| ALAT Increased: Grade 3 |
0
0%
|
0
0%
|
3
8.1%
|
0
0%
|
| ALAT Increased: Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Blood Bilirubin Increased:All Grades |
1
5.9%
|
0
0%
|
9
24.3%
|
1
25%
|
| Blood Bilirubin Increased:Grade 1 |
0
0%
|
0
0%
|
4
10.8%
|
1
25%
|
| Blood Bilirubin Increased:Grade 2 |
0
0%
|
0
0%
|
3
8.1%
|
0
0%
|
| Blood Bilirubin Increased:Grade 3 |
1
5.9%
|
0
0%
|
2
5.4%
|
0
0%
|
| Blood Bilirubin Increased:Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hypocalcemia: All Grades |
6
35.3%
|
1
33.3%
|
7
18.9%
|
0
0%
|
| Hypocalcemia: Grade 1 |
4
23.5%
|
1
33.3%
|
5
13.5%
|
0
0%
|
| Hypocalcemia: Grade 2 |
1
5.9%
|
0
0%
|
0
0%
|
0
0%
|
| Hypocalcemia: Grade 3 |
1
5.9%
|
0
0%
|
2
5.4%
|
0
0%
|
| Hypocalcemia: Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine increased: All Grades |
5
29.4%
|
1
33.3%
|
15
40.5%
|
0
0%
|
| Creatinine increased: Grade 1 |
3
17.6%
|
1
33.3%
|
8
21.6%
|
0
0%
|
| Creatinine increased: Grade 2 |
1
5.9%
|
0
0%
|
4
10.8%
|
0
0%
|
| Creatinine increased: Grade 3 |
0
0%
|
0
0%
|
2
5.4%
|
0
0%
|
| Creatinine increased: Grade 4 |
1
5.9%
|
0
0%
|
1
2.7%
|
0
0%
|
Adverse Events
| Time Frame | All AEs were collected from the date of signing the consent up to 30 days after the last dose (maximum of 1959 days) regardless of seriousness or relationship to investigational product. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Reported AEs and deaths are TEAEs that is AEs and deaths that developed/worsened during the 'on treatment period' (time from the first dose of any study drug up to 30 days after the last dose of any study drug). Analysis was performed on safety population. | |||||||
| Arm/Group Title | SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen | ||||
| Arm/Group Description | Participants received SAR245408 400 mg once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). | Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab). | Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). | Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab). | ||||
All Cause Mortality |
||||||||
| SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/17 (5.9%) | 0/3 (0%) | 3/37 (8.1%) | 0/4 (0%) | ||||
Serious Adverse Events |
||||||||
| SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/17 (52.9%) | 1/3 (33.3%) | 10/37 (27%) | 0/4 (0%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Neutropenia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Thrombocytopenia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Cardiac disorders | ||||||||
| Angina Unstable | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Constipation | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Gastritis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Intestinal Obstruction | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Upper Gastrointestinal Haemorrhage | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| General disorders | ||||||||
| Disease Progression | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Pyrexia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Systemic Inflammatory Response Syndrome | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Cholangitis Acute | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Cholecystitis Acute | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Infections and infestations | ||||||||
| Abscess Limb | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Acute Sinusitis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Catheter Site Infection | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Cellulitis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Intervertebral Discitis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Osteomyelitis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pneumonia | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Sepsis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Staphylococcal Skin Infection | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Urinary Tract Infection | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Wound Infection | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Femur Fracture | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Investigations | ||||||||
| Alanine Aminotransferase Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Lipase Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Troponin Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Hypercalcaemia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Tumour Lysis Syndrome | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acute Leukaemia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Acute Myeloid Leukaemia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Nervous system disorders | ||||||||
| Encephalopathy | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Haemorrhage Intracranial | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Headache | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Syncope | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Acute Kidney Injury | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Renal Colic | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic Obstructive Pulmonary Disease | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Dyspnoea | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Pleural Effusion | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Respiratory Distress | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Vascular disorders | ||||||||
| Haematoma | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Hypotension | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| SAR245408: Monotherapy | SAR245408: Combination Regimen | SAR245409: Monotherapy | SAR245409: Combination Regimen | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/17 (88.2%) | 3/3 (100%) | 34/37 (91.9%) | 3/4 (75%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 3/17 (17.6%) | 4 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Iron Deficiency Anaemia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Leukocytosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Leukopenia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Lymphopenia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 1/4 (25%) | 1 |
| Neutropenia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Splenomegaly | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Thrombocytopenia | 2/17 (11.8%) | 3 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 1/4 (25%) | 1 |
| Cardiac disorders | ||||||||
| Bradycardia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Cardiac Arrest | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Cardiomegaly | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Coronary Artery Disease | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Pericardial Effusion | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Sinus Bradycardia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Tachycardia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Ventricular Extrasystoles | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Ventricular Tachycardia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Cerumen Impaction | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Deafness Unilateral | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Ear Discomfort | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hyperacusis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hypoacusis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Tinnitus | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Vertigo | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Endocrine disorders | ||||||||
| Hyperthyroidism | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hypothyroidism | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Eye disorders | ||||||||
| Cataract | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Corneal Scar | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Dry Eye | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Retinal Vein Occlusion | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Visual Impairment | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Vitreous Floaters | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal Distension | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Abdominal Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Abdominal Pain Lower | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Abdominal Tenderness | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Abdominal Wall Haematoma | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Anal Incontinence | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Ascites | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Chapped Lips | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Constipation | 4/17 (23.5%) | 4 | 1/3 (33.3%) | 1 | 7/37 (18.9%) | 7 | 1/4 (25%) | 1 |
| Diarrhoea | 7/17 (41.2%) | 8 | 2/3 (66.7%) | 2 | 14/37 (37.8%) | 14 | 3/4 (75%) | 3 |
| Dyspepsia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Dysphagia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Faeces Discoloured | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Flatulence | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Gastrooesophageal Reflux Disease | 3/17 (17.6%) | 4 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Hypoaesthesia Oral | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Nausea | 5/17 (29.4%) | 5 | 2/3 (66.7%) | 2 | 10/37 (27%) | 10 | 0/4 (0%) | 0 |
| Pancreatic Failure | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Peptic Ulcer Haemorrhage | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Salivary Gland Enlargement | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Short-Bowel Syndrome | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Vomiting | 2/17 (11.8%) | 2 | 2/3 (66.7%) | 2 | 7/37 (18.9%) | 7 | 1/4 (25%) | 1 |
| General disorders | ||||||||
| Asthenia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Catheter Site Discharge | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Chest Pain | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Chills | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Face Oedema | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Facial Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 1/4 (25%) | 1 |
| Fatigue | 8/17 (47.1%) | 9 | 1/3 (33.3%) | 1 | 8/37 (21.6%) | 8 | 0/4 (0%) | 0 |
| Gait Disturbance | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| General Physical Health Deterioration | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Localised Oedema | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Malaise | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Mucosal Inflammation | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Non-Cardiac Chest Pain | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Oedema Peripheral | 3/17 (17.6%) | 3 | 1/3 (33.3%) | 1 | 4/37 (10.8%) | 4 | 0/4 (0%) | 0 |
| Pain | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Performance Status Decreased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Peripheral Swelling | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pyrexia | 4/17 (23.5%) | 4 | 1/3 (33.3%) | 1 | 6/37 (16.2%) | 6 | 0/4 (0%) | 0 |
| Suprapubic Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Immune system disorders | ||||||||
| Contrast Media Allergy | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Drug Hypersensitivity | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Hypersensitivity | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Infections and infestations | ||||||||
| Abscess Limb | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Bronchitis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 4/37 (10.8%) | 5 | 0/4 (0%) | 0 |
| Cellulitis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Chronic Sinusitis | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Conjunctivitis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Eye Infection | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Fungal Skin Infection | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Gastroenteritis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Gastrointestinal Viral Infection | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hepatitis C | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Herpes Zoster | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Hordeolum | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Influenza | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Lower Respiratory Tract Infection | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Nasopharyngitis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Onychomycosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Oral Candidiasis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Pneumonia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Postoperative Wound Infection | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Respiratory Tract Infection | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Rhinitis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Sepsis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Sinusitis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 5/37 (13.5%) | 5 | 1/4 (25%) | 1 |
| Skin Infection | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Tooth Abscess | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Tooth Infection | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 1/4 (25%) | 1 |
| Upper Respiratory Tract Infection | 3/17 (17.6%) | 3 | 0/3 (0%) | 0 | 8/37 (21.6%) | 8 | 1/4 (25%) | 1 |
| Urinary Tract Infection | 2/17 (11.8%) | 2 | 1/3 (33.3%) | 1 | 6/37 (16.2%) | 6 | 0/4 (0%) | 0 |
| Viral Upper Respiratory Tract Infection | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Accidental Overdose | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Contusion | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Fall | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Foreign Body In Eye | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Incision Site Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Ligament Injury | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Limb Injury | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Muscle Strain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Rib Fracture | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Skin Abrasion | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Spinal Compression Fracture | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Wound Dehiscence | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Investigations | ||||||||
| Activated Partial Thromboplastin Time Prolonged | 1/17 (5.9%) | 3 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Alanine Aminotransferase Increased | 0/17 (0%) | 0 | 2/3 (66.7%) | 2 | 4/37 (10.8%) | 5 | 0/4 (0%) | 0 |
| Amylase Increased | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 6/37 (16.2%) | 6 | 0/4 (0%) | 0 |
| Aspartate Aminotransferase Increased | 0/17 (0%) | 0 | 2/3 (66.7%) | 2 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Bilirubin Conjugated Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Blood Alkaline Phosphatase Increased | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Blood Bilirubin Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Blood Cholesterol Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Blood Creatinine Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Blood Lactate Dehydrogenase Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Blood Phosphorus Decreased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Blood Urea Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Body Temperature Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Breath Sounds Abnormal | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Breath Sounds Absent | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Cardiac Murmur | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Chest X-Ray Abnormal | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Electrocardiogram Qt Prolonged | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Heart Rate Irregular | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| International Normalised Ratio Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Lipase Increased | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 8/37 (21.6%) | 8 | 0/4 (0%) | 0 |
| Neutrophil Count Decreased | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Nuclear Magnetic Resonance Imaging Brain Abnormal | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Platelet Count Decreased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Procalcitonin Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Protein Urine Present | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Prothrombin Time Prolonged | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Red Blood Cell Count Decreased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Red Blood Cells Urine | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Urine Analysis Abnormal | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Urine Protein/Creatinine Ratio Increased | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Vitamin B12 Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Vitamin D Decreased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Weight Decreased | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 4/37 (10.8%) | 4 | 0/4 (0%) | 0 |
| Weight Increased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| White Blood Cell Count Decreased | 1/17 (5.9%) | 2 | 1/3 (33.3%) | 1 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| White Blood Cell Count Increased | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| White Blood Cells Urine | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| White Blood Cells Urine Positive | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Decreased Appetite | 2/17 (11.8%) | 2 | 1/3 (33.3%) | 1 | 5/37 (13.5%) | 5 | 0/4 (0%) | 0 |
| Dehydration | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Diabetes Mellitus | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Gout | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hypercalcaemia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hypercholesterolaemia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hyperglycaemia | 1/17 (5.9%) | 1 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Hyperkalaemia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hyperlipidaemia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hyperphosphataemia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hypoalbuminaemia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Hypocalcaemia | 1/17 (5.9%) | 1 | 1/3 (33.3%) | 1 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hypokalaemia | 1/17 (5.9%) | 1 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Hypomagnesaemia | 3/17 (17.6%) | 3 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hyponatraemia | 2/17 (11.8%) | 3 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Hypophosphataemia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Metabolic Acidosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Vitamin D Deficiency | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Back Pain | 4/17 (23.5%) | 4 | 1/3 (33.3%) | 1 | 4/37 (10.8%) | 4 | 0/4 (0%) | 0 |
| Bursitis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Flank Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Groin Pain | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Joint Swelling | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Muscle Spasms | 3/17 (17.6%) | 3 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Muscle Twitching | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Muscular Weakness | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Musculoskeletal Chest Pain | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Musculoskeletal Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Myalgia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Neck Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Osteoarthritis | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Osteoporosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pain In Extremity | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pain In Jaw | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pathological Fracture | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Periarthritis | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Pubic Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Scoliosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Basal Cell Carcinoma | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Squamous Cell Carcinoma Of Skin | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Tumour Pain | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Nervous system disorders | ||||||||
| Amnesia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Aphasia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Ataxia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Cognitive Disorder | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Dizziness | 3/17 (17.6%) | 3 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 1/4 (25%) | 1 |
| Dizziness Postural | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Dysarthria | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Headache | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 6/37 (16.2%) | 6 | 0/4 (0%) | 0 |
| Hypoaesthesia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Lethargy | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Memory Impairment | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Neuropathy Peripheral | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Paraesthesia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Partial Seizures | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 1/4 (25%) | 1 |
| Peripheral Sensory Neuropathy | 0/17 (0%) | 0 | 2/3 (66.7%) | 2 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Sciatica | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Seizure | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Syncope | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Tremor | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Visual Field Defect | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Product Issues | ||||||||
| Thrombosis In Device | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Anxiety | 4/17 (23.5%) | 4 | 0/3 (0%) | 0 | 4/37 (10.8%) | 4 | 0/4 (0%) | 0 |
| Confusional State | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Depression | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Emotional Distress | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hallucination | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Insomnia | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Post-Traumatic Stress Disorder | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Chronic Kidney Disease | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Dysuria | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Glycosuria | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Haematuria | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Haemoglobinuria | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Hydronephrosis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Micturition Urgency | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Nephrolithiasis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Nocturia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Oliguria | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pollakiuria | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Proteinuria | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Renal Failure | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Urinary Hesitation | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Urinary Incontinence | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Urinary Retention | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Urinary Tract Pain | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Urine Flow Decreased | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Benign Prostatic Hyperplasia | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Prostatic Obstruction | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Testicular Swelling | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Atelectasis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Cough | 0/17 (0%) | 0 | 2/3 (66.7%) | 2 | 8/37 (21.6%) | 8 | 0/4 (0%) | 0 |
| Dysphonia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Dyspnoea | 3/17 (17.6%) | 3 | 1/3 (33.3%) | 1 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Dyspnoea Exertional | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Hypoxia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Nasal Congestion | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Oropharyngeal Pain | 1/17 (5.9%) | 3 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Paranasal Sinus Discomfort | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pleural Effusion | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Pneumonitis | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Productive Cough | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 4/37 (10.8%) | 4 | 0/4 (0%) | 0 |
| Rhinitis Allergic | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Rhinorrhoea | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Sleep Apnoea Syndrome | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Tachypnoea | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Tonsillar Inflammation | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Wheezing | 1/17 (5.9%) | 1 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Actinic Keratosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Alopecia | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Blister | 1/17 (5.9%) | 1 | 1/3 (33.3%) | 1 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Decubitus Ulcer | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Dermatitis Acneiform | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Dry Skin | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Erythema | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Hyperhidrosis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Ingrowing Nail | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 2 | 0/4 (0%) | 0 |
| Nail Pigmentation | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Night Sweats | 1/17 (5.9%) | 2 | 0/3 (0%) | 0 | 3/37 (8.1%) | 3 | 0/4 (0%) | 0 |
| Onychoclasis | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Pain Of Skin | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Palmar-Plantar Erythrodysaesthesia Syndrome | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Petechiae | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Photosensitivity Reaction | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Precancerous Skin Lesion | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Pruritus | 1/17 (5.9%) | 1 | 2/3 (66.7%) | 2 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Pruritus Generalised | 1/17 (5.9%) | 1 | 1/3 (33.3%) | 1 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Psoriasis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Rash | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Rash Generalised | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Rash Macular | 2/17 (11.8%) | 2 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Rash Maculo-Papular | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Rash Pruritic | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Scab | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Seborrhoeic Dermatitis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Skin Hyperpigmentation | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Skin Lesion | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Skin Mass | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Swelling Face | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Urticaria | 1/17 (5.9%) | 1 | 0/3 (0%) | 0 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Vascular disorders | ||||||||
| Brachiocephalic Vein Thrombosis | 0/17 (0%) | 0 | 1/3 (33.3%) | 1 | 0/37 (0%) | 0 | 0/4 (0%) | 0 |
| Deep Vein Thrombosis | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 2/37 (5.4%) | 2 | 0/4 (0%) | 0 |
| Flushing | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hot Flush | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Hypertension | 5/17 (29.4%) | 5 | 1/3 (33.3%) | 1 | 8/37 (21.6%) | 8 | 0/4 (0%) | 0 |
| Hypotension | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Lymphoedema | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
| Systolic Hypertension | 0/17 (0%) | 0 | 0/3 (0%) | 0 | 1/37 (2.7%) | 1 | 0/4 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | 800-633-1610 ext 1# |
| Contact-US@sanofi.com |
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT01587040
Other Study ID Numbers:
- TED12414
- 2011-006140-78
- U1111-1124-1403
First Posted:
Apr 27, 2012
Last Update Posted:
Apr 19, 2022
Last Verified:
Mar 1, 2022