Everolimus in Combination With Imatinib in Patients With Glivec Refractory/Resistant Gastrointestinal Stromal Tumors
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01275222
Collaborator
(none)
117
16
6
69.7
7.3
0.1
Study Details
Study Description
Brief Summary
This trial was a Phase I/II, non-randomized, open label, multi-center study, following a sequential 2-part design.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The first part, Phase I, was designed to assess whether there is a pharmacokinetic interaction between Glivec/Gleevec (imatinib) and RAD001(everolimus) as well as to collect safety data when these two drugs are co-administered. The second part, (Phase II), was designed to assess the potential efficacy of the combination in imatinib-resistant GIST patients in two strata of patients:
-
Patients resistant to imatinib as first-line drug therapy and in whom the maximum tolerated dose was at least 600 mg/d (Stratum 1, first-line resistant/refractory)
-
Patients resistant to imatinib as well as to post-imatinib drug therapy (Stratum 2, post second-line therapy).
It was decided to discontinue the study and close to further enrollment based on alternative treatment options that became available. Phase 1 and Phase 2 Stratum 1 were ended early on 02-Nov-2006. Investigators were allowed to complete the enrollment in the Phase 2 Stratum 2.
Study Design
Study Type:
Interventional
Actual Enrollment
:
117 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I-II, Open-label Study of RAD001 in Combination With Glivec®/Gleevec™ (Imatinib) in Patients With Glivec/Gleevec-refractory/Resistant Gastrointestinal Stromal Tumors.
Actual Study Start Date
:
Nov 13, 2002
Actual Primary Completion Date
:
Sep 3, 2008
Actual Study Completion Date
:
Sep 3, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase l: RAD001 20mg/week RAD001 20 mg was given once a week. |
Drug: RAD001
RAD001 was in tablets of 0.5 mg, 1.0 mg, 2.5 mg and 5.0 mg strength and was taken by mouth, once a week or once a day depending upon the treatment group the patient was enrolled into.
Other Names:
|
| Experimental: Phase l: RAD001 2.5mg/day + Glivec 600mg/day RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. |
Drug: RAD001
RAD001 was in tablets of 0.5 mg, 1.0 mg, 2.5 mg and 5.0 mg strength and was taken by mouth, once a week or once a day depending upon the treatment group the patient was enrolled into.
Other Names:
Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib)
Glivec/Gleevec was supplied as commercialized 100 mg and 400 mg tablets. Gleevec/Glivec was provided as capsules of 100 mg strength in bottles containing 60 capsules each. The use of this supply was study center specific. Glivec/Gleevec was taken, by mouth, at a dose of 300 mg twice a day. The Glivec/Gleevec regimen was changed from 600 mg once a day to 300 mg BID, by an amendment since taking too many tablets at once was difficult for patients with gastro-intestinal disease. In the phase II part of the study all patients received Glivec 600 mg/day.
Other Names:
|
| Experimental: Phase l: RAD001 5mg/day + Glivec 600mg/day RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. |
Drug: RAD001
RAD001 was in tablets of 0.5 mg, 1.0 mg, 2.5 mg and 5.0 mg strength and was taken by mouth, once a week or once a day depending upon the treatment group the patient was enrolled into.
Other Names:
Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib)
Glivec/Gleevec was supplied as commercialized 100 mg and 400 mg tablets. Gleevec/Glivec was provided as capsules of 100 mg strength in bottles containing 60 capsules each. The use of this supply was study center specific. Glivec/Gleevec was taken, by mouth, at a dose of 300 mg twice a day. The Glivec/Gleevec regimen was changed from 600 mg once a day to 300 mg BID, by an amendment since taking too many tablets at once was difficult for patients with gastro-intestinal disease. In the phase II part of the study all patients received Glivec 600 mg/day.
Other Names:
|
| Experimental: Phase l: RAD001 2.5mg/day + Glivec 800mg/day RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. |
Drug: RAD001
RAD001 was in tablets of 0.5 mg, 1.0 mg, 2.5 mg and 5.0 mg strength and was taken by mouth, once a week or once a day depending upon the treatment group the patient was enrolled into.
Other Names:
Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib)
Glivec/Gleevec was supplied as commercialized 100 mg and 400 mg tablets. Gleevec/Glivec was provided as capsules of 100 mg strength in bottles containing 60 capsules each. The use of this supply was study center specific. Glivec/Gleevec was taken, by mouth, at a dose of 300 mg twice a day. The Glivec/Gleevec regimen was changed from 600 mg once a day to 300 mg BID, by an amendment since taking too many tablets at once was difficult for patients with gastro-intestinal disease. In the phase II part of the study all patients received Glivec 600 mg/day.
Other Names:
|
| Experimental: Phase ll - Stratum l (first-line resistant/refractory): RAD001 2.5mg/day + Glivec 600mg/day All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
Drug: RAD001
RAD001 was in tablets of 0.5 mg, 1.0 mg, 2.5 mg and 5.0 mg strength and was taken by mouth, once a week or once a day depending upon the treatment group the patient was enrolled into.
Other Names:
Drug: Imatinib 800mg/day (Glevec is the brand name for imatinib)
Glivec/Gleevec was supplied as commercialized 100 mg and 400 mg tablets. Gleevec/Glivec was provided as capsules of 100 mg strength in bottles containing 60 capsules each. The use of this supply was study center specific. Glivec/Gleevec was taken, by mouth. In the phase II part of the study all patients received Glivec 600 mg/day, except for 2 patients who received Glivec at a dose of 800 mg/day. This dose was permitted in Phase II as it was found to be safe in Phase I.
Other Names:
|
| Experimental: Phase ll - Stratum ll: (post second-line therapy): RAD001 2.5mg/day + Glivec 600mg/day All post-second-line patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day |
Drug: RAD001
RAD001 was in tablets of 0.5 mg, 1.0 mg, 2.5 mg and 5.0 mg strength and was taken by mouth, once a week or once a day depending upon the treatment group the patient was enrolled into.
Other Names:
Drug: Imatinib 800mg/day (Glevec is the brand name for imatinib)
Glivec/Gleevec was supplied as commercialized 100 mg and 400 mg tablets. Gleevec/Glivec was provided as capsules of 100 mg strength in bottles containing 60 capsules each. The use of this supply was study center specific. Glivec/Gleevec was taken, by mouth. In the phase II part of the study all patients received Glivec 600 mg/day, except for 2 patients who received Glivec at a dose of 800 mg/day. This dose was permitted in Phase II as it was found to be safe in Phase I.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs): Phase I & II [4 - 8 weeks]
Assessed safety and tolerability of the combination administration of RAD001 and imatinib when given to patients with imatinib-refractory gastro-intestinal stromal tumors (GIST) by number of participants with adverse events.
- Best Overall Response (BOR) as Assessed by Overall Response (Complete Response (CR) & Partial Response (PR)) - Phase I & II [6 - 8 weeks]
Assessed clinical efficacy of the combination regimen in this patient population per BOR by Overall response (CR + PR). Complete response: Disappearance of all target lesions; Partial response: ≥ 30% decrease in the sum of the longest diameter of target lesions compared to baseline (and not ≥20% increase compared to smallest sum).
- Trough Concentrations for RAD001 and for Imatinib - Phase II [Part II Daily regimen: Baseline, Days 8, 15 and thereafter approximately every two months starting at month 3 whenever possible]
Assessed the pharmacokinetics (PK) of the combination administration of RAD001 and imatinib in this patient population.
- Overall Survival (OS) - Phase I & II [about 60 months]
Assessed clinical efficacy of the combination regimen in this patient population per Overall Survival (OS). Overall survival was defined as the time from date of start of treatment to date of death due to any cause. For patients still receiving study medication at the time of the analysis, survival was censored at the date of last examination. If a patient was not known to have died but was no longer continuing with study medication, survival was censored at the date of last contact.
- 4-Month Progression-free Survival (PFS) Rate - Phase II [about 4 months]
Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. Per protocol (PP) population includes patients with no known overall lesion response during 4 months +/- 2 weeks, or who later had response of CR/PR/stable disease (SD). PP population excludes patients with no known response during 4 months + / -2 weeks and no subsequent CR/PR/SD.
- Progression-free Survival (PFS) - Phase II [about 60 months]
Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. If a patient had not progressed or died, progression-free survival was censored at the time of last adequate tumor assessment. According to the study protocol no tumor assessments were performed after discontinuation of treatment with study drug. Therefore, for all patients who discontinued treatment without a documented progression but died thereafter, death was considered as PFS event only if it occurred within the regular safety follow-up of 28 days after discontinuation. Otherwise, the PFS time was censored at the last adequate tumor assessment.
Secondary Outcome Measures
- mTOR Pathway Activity Before Treatment, and Inhibition of mTOR Pathway Activity During Treatment as a Predictive Factor of Response, as Shown by Molecular Pathological Examination of the Tumor. [about 60 months]
assess mTOR pathway activity before treatment, and inhibition of mTOR pathway activity during treatment as a predictive factor of response, as shown by molecular pathological examination of the tumor.
- Relationship Between Drug-induced Changes in the Principal Molecular Marker of Intratumoral mTOR Activity and Changes in Other Molecular Markers of Tumoral Activity (e.g. Indicators of Pathway Activity, Cell Proliferation and Apoptosis). [about 60 months]
assess the relationship between drug-induced changes in the principal molecular marker of intratumoral mTOR activity and changes in other molecular markers of tumoral activity (e.g. indicators of pathway activity, cell proliferation and apoptosis).
- Relationship Between Drug-induced Changes in Tumoral Metabolism, as Shown by Functional Imaging With 18F-fluorodeoxyglucose Positron Emission Tomography (FDC-PET), With Clinical Outcome and Changes in Molecular Pathology. [about 60 months]
assess the relationship between drug-induced changes in tumoral metabolism, as shown by functional imaging with 18F-fluorodeoxyglucose positron emission tomography (FDC-PET), with clinical outcome and changes in molecular pathology.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Phase l:
-
Patients aged ≥ 18 years
-
Patients with a histologically proven diagnosis of GIST and clinical evidence of resistance to imatinib despite at least 4 months continuous treatment with imatinib
-
Patients with at least 2 months at a dosage of ≥ 600 mg/day (progression despite uninterrupted therapy for 2 months at ≥800 mg/d for patients entering the Phase I cohort investigating the 800 mg/d dose)
-
Patients were to have at least one measurable lesion (longest diameter ≥20 mm on conventional CT or MRI scan
-
patients were to have ≥10 mm on spiral CT) and were to have a WHO Performance Status Score ≤ 2.
-
Patients also were to have adequate bone marrow, liver and renal function on imatinib treatment, as specified in the protocol
Phase ll:
• For Phase II (Stratum 2) patients must have progression on other 2nd line drug therapies following prior progression on imatinib (Stratum 2)
Exclusion Criteria:
-
Women who are pregnant or breast-feeding
-
Patients presenting with known or symptomatic CNS metastases or leptomeningeal involvement
-
Patients with any concurrent major medical condition liable to compromise the patient's participation in the study (e.g. known HIV infection, uncontrolled diabetes, serious cardiac dysrhythmia or condition, New York Heart Association classification of III or IV, congestive cardiac failure, myocardial infarction with 6 months, unstable angina, chronic or acute renal or liver disease, uncontrolled infections including abscess or fistulae, etc.)
-
Patients with a history of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer
-
Patients unwilling to or unable to comply with the protocol
-
Patients who are receiving glucocorticoids (only if the p70s6 kinase1 assay is being performed), since these have been shown to inhibit p70s6 kinase1 activity.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dana Farber Cancer Institute Dept of Sarcoma Oncology | Boston | Massachusetts | United States | 02215 |
| 2 | College of Physicians and Surgeons of Columbia University | New York | New York | United States | 10032 |
| 3 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 4 | Novartis Investigative Site | Edegem | Antwerpen | Belgium | 2650 |
| 5 | Novartis Investigative Site | Leuven | Belgium | 3000 | |
| 6 | Novartis Investigative Site | Bordeaux | France | 33076 | |
| 7 | Novartis Investigative Site | Lille Cedex | France | 59020 | |
| 8 | Novartis Investigative Site | Lyon | France | F-69373 | |
| 9 | Novartis Investigative Site | Marseille Cedex 05 | France | 13385 | |
| 10 | Novartis Investigative Site | Villejuif Cedex | France | 94805 | |
| 11 | Novartis Investigative Site | Berlin | Germany | 13125 | |
| 12 | Novartis Investigative Site | Frankfurt | Germany | 60488 | |
| 13 | Novartis Investigative Site | Hamburg | Germany | 20246 | |
| 14 | Novartis Investigative Site | Koeln | Germany | 50937 | |
| 15 | Novartis Investigative Site | Muenchen | Germany | 81377 | |
| 16 | Novartis Investigative Site | Tübingen | Germany | 72076 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01275222
Other Study ID Numbers:
- CRAD001C2206
First Posted:
Jan 12, 2011
Last Update Posted:
Jun 25, 2021
Last Verified:
Jun 1, 2021
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
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This trial was a Phase I/II study, following a sequential 2-part design. The 1st part was designed to assess whether there was a pharmacokinetic interaction between Glivec/Gleevec and RAD001. The 2nd part was designed to assess the potential efficacy of the combination in Glivec/Gleevec-resistant GIST patients in 2 strata of patients. |
|---|---|
| Pre-assignment Detail | An estimated maximum of 130 patients was planned to be enrolled into the study. In Phase I, there were 42 patients enrolled. In Phase II, there were 75 patients enrolled. 3 patients were excluded from all analyses due to a major protocol violation. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Period Title: Phase l by Treatment | ||||||
| STARTED | 13 | 13 | 5 | 11 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 13 | 13 | 5 | 11 | 0 | 0 |
| Period Title: Phase l by Treatment | ||||||
| STARTED | 0 | 0 | 0 | 0 | 28 | 47 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 1 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 28 | 46 |
Baseline Characteristics
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | Total of all reporting groups |
| Overall Participants | 13 | 13 | 5 | 11 | 28 | 47 | 117 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [Years] |
55.6
(13.16)
|
59.3
(12.54)
|
57.9
(12.81)
|
||||
| Age (Years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [Years] |
53.5
(5.25)
|
52.2
(14.11)
|
53.8
(11.95)
|
61.9
(13.25)
|
55.3
(11.80)
|
||
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
2
15.4%
|
3
23.1%
|
4
80%
|
2
18.2%
|
7
25%
|
16
34%
|
34
29.1%
|
| Male |
11
84.6%
|
10
76.9%
|
1
20%
|
9
81.8%
|
21
75%
|
31
66%
|
83
70.9%
|
| Race/Ethnicity, Customized (Number) [Number] | |||||||
| Caucasian |
13
100%
|
12
92.3%
|
5
100%
|
11
100%
|
27
96.4%
|
47
100%
|
115
98.3%
|
| Black |
0
0%
|
1
7.7%
|
0
0%
|
0
0%
|
1
3.6%
|
0
0%
|
2
1.7%
|
Outcome Measures
| Title | Number of Participants With Adverse Events (AEs): Phase I & II |
|---|---|
| Description | Assessed safety and tolerability of the combination administration of RAD001 and imatinib when given to patients with imatinib-refractory gastro-intestinal stromal tumors (GIST) by number of participants with adverse events. |
| Time Frame | 4 - 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the Safety population for Phase I. All patients were included in the Safety population for Phase II. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 13 | 13 | 5 | 11 | 28 | 47 |
| Number [Participants] |
13
100%
|
13
100%
|
5
100%
|
11
100%
|
27
96.4%
|
47
100%
|
| Title | Best Overall Response (BOR) as Assessed by Overall Response (Complete Response (CR) & Partial Response (PR)) - Phase I & II |
|---|---|
| Description | Assessed clinical efficacy of the combination regimen in this patient population per BOR by Overall response (CR + PR). Complete response: Disappearance of all target lesions; Partial response: ≥ 30% decrease in the sum of the longest diameter of target lesions compared to baseline (and not ≥20% increase compared to smallest sum). |
| Time Frame | 6 - 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the ITT population. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 13 | 13 | 5 | 11 | 28 | 47 |
| Number (95% Confidence Interval) [Percentage of Participants] |
0
0%
|
1
7.7%
|
0
0%
|
0.0
0%
|
0
0%
|
1
2.1%
|
| Title | Trough Concentrations for RAD001 and for Imatinib - Phase II |
|---|---|
| Description | Assessed the pharmacokinetics (PK) of the combination administration of RAD001 and imatinib in this patient population. |
| Time Frame | Part II Daily regimen: Baseline, Days 8, 15 and thereafter approximately every two months starting at month 3 whenever possible |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) population: The PK population included 18% of Stratum I patients and 47% of Stratum II patients |
| Arm/Group Title | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|
| Arm/Group Description | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 5 | 22 |
| Week 2: RAD001 |
24.300
|
12.100
|
| Week 3: RAD001 |
19.900
|
12.750
|
| Week 9: RAD001 |
10.950
|
|
| Month 4: RAD001 |
7.840
|
|
| Baseline: Imatinib |
472.00
|
501.50
|
| Week 2: Imatinib |
626.50
|
540.00
|
| Week 3: Imatinib |
572.00
|
718.00
|
| Week 9: Imatinib |
899.0
|
|
| Month 4: Imatinib |
333.00
|
446.00
|
| Month 6: Imatinib |
181.00
|
2040.00
|
| Month 8: Imatinib |
575.00
|
|
| Month 12: Imatinib |
324.00
|
| Title | Overall Survival (OS) - Phase I & II |
|---|---|
| Description | Assessed clinical efficacy of the combination regimen in this patient population per Overall Survival (OS). Overall survival was defined as the time from date of start of treatment to date of death due to any cause. For patients still receiving study medication at the time of the analysis, survival was censored at the date of last examination. If a patient was not known to have died but was no longer continuing with study medication, survival was censored at the date of last contact. |
| Time Frame | about 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the ITT population for phase I. All patients were included in the ITT population for phase II. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 13 | 13 | 5 | 11 | 28 | 47 |
| Median (95% Confidence Interval) [months] |
9.4
|
10.9
|
18.7
|
NA
|
14.9
|
10.7
|
| Title | mTOR Pathway Activity Before Treatment, and Inhibition of mTOR Pathway Activity During Treatment as a Predictive Factor of Response, as Shown by Molecular Pathological Examination of the Tumor. |
|---|---|
| Description | assess mTOR pathway activity before treatment, and inhibition of mTOR pathway activity during treatment as a predictive factor of response, as shown by molecular pathological examination of the tumor. |
| Time Frame | about 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic population: Molecular pathology and pharmacogenomic assessments were planned, but not carried out due to an alternative therapy that became available after the initiation of this study. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Relationship Between Drug-induced Changes in the Principal Molecular Marker of Intratumoral mTOR Activity and Changes in Other Molecular Markers of Tumoral Activity (e.g. Indicators of Pathway Activity, Cell Proliferation and Apoptosis). |
|---|---|
| Description | assess the relationship between drug-induced changes in the principal molecular marker of intratumoral mTOR activity and changes in other molecular markers of tumoral activity (e.g. indicators of pathway activity, cell proliferation and apoptosis). |
| Time Frame | about 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic population: Molecular pathology and pharmacogenomic assessments were planned, but not carried out due to an alternative therapy that became available after the initiation of this study. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Relationship Between Drug-induced Changes in Tumoral Metabolism, as Shown by Functional Imaging With 18F-fluorodeoxyglucose Positron Emission Tomography (FDC-PET), With Clinical Outcome and Changes in Molecular Pathology. |
|---|---|
| Description | assess the relationship between drug-induced changes in tumoral metabolism, as shown by functional imaging with 18F-fluorodeoxyglucose positron emission tomography (FDC-PET), with clinical outcome and changes in molecular pathology. |
| Time Frame | about 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| PET scans at baseline and as follow-up were planned to assess functional changes in tumors for patients on treatment. This analysis was not carried out due to alternative therapy that became available after the initiation of this study. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | 4-Month Progression-free Survival (PFS) Rate - Phase II |
|---|---|
| Description | Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. Per protocol (PP) population includes patients with no known overall lesion response during 4 months +/- 2 weeks, or who later had response of CR/PR/stable disease (SD). PP population excludes patients with no known response during 4 months + / -2 weeks and no subsequent CR/PR/SD. |
| Time Frame | about 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per Protocol population: The per-protocol population included 82% of Stratum I patients and 75% of Stratum II patients. |
| Arm/Group Title | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|
| Arm/Group Description | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 23 | 35 |
| Number (95% Confidence Interval) [Percentage of participants] |
17.4
133.8%
|
37.1
285.4%
|
| Title | Progression-free Survival (PFS) - Phase II |
|---|---|
| Description | Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. If a patient had not progressed or died, progression-free survival was censored at the time of last adequate tumor assessment. According to the study protocol no tumor assessments were performed after discontinuation of treatment with study drug. Therefore, for all patients who discontinued treatment without a documented progression but died thereafter, death was considered as PFS event only if it occurred within the regular safety follow-up of 28 days after discontinuation. Otherwise, the PFS time was censored at the last adequate tumor assessment. |
| Time Frame | about 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: All patients were included in the ITT population for Phase II. |
| Arm/Group Title | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|
| Arm/Group Description | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 28 | 47 |
| Median (95% Confidence Interval) [months] |
1.9
|
3.5
|
| Title | All Collected Deaths |
|---|---|
| Description | On treatment deaths were collected from FPFT up to 28 days after study drug discontinuation, for a maximum duration of 35.52 months (treatment duration ranged from 0.36 to to 35.52 months for the phase I part) and a maximum duration of 21.88 months (treatment duration of 0.16 to 21.88 months for the phase II part). Deaths post treatment survival follow up were collected after the on treatment period, up to 70 months. |
| Time Frame | approx. 35.52 months, approx. 70 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the ITT population for phase I. All patients were included in the ITT population for phase II. |
| Arm/Group Title | Phase l: RAD001 20mg/Week | Phase l: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase l: RAD001 5mg/Day + Glivec 600mg/Day | Phase l: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) |
|---|---|---|---|---|---|---|
| Arm/Group Description | RAD001 20 mg was given once a week. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Measure Participants | 13 | 13 | 5 | 11 | 28 | 47 |
| Total Deaths |
12
92.3%
|
8
61.5%
|
3
60%
|
3
27.3%
|
9
32.1%
|
22
46.8%
|
| Deaths on-treatment |
2
15.4%
|
3
23.1%
|
0
0%
|
2
18.2%
|
3
10.7%
|
6
12.8%
|
Adverse Events
| Time Frame | On-treatment deaths were collected from FPFT up to 28 days after study drug discontinuation, for a maximum duration of 35.52 months (treatment duration ranged from 0.36 to to 35.52 months for Phase I part) and a maximum duration of 21.88 months (treatment duration of 0.16 to 21.88 months for the Phase II part). | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Event: Any sign or symptom that occurs during the study treatment plus 28 days post treatment. | |||||||||||
| Arm/Group Title | Phase I - RAD001 20mg/Week ++ Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase I: RAD001 5mg/Day + Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) | ||||||
| Arm/Group Description | RAD001 20 mg was given in combination with Glivec/Gleevec 600mg/day | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | All post second-line therapy patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. | ||||||
All Cause Mortality |
||||||||||||
| Phase I - RAD001 20mg/Week ++ Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase I: RAD001 5mg/Day + Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| Phase I - RAD001 20mg/Week ++ Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase I: RAD001 5mg/Day + Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/13 (30.8%) | 7/13 (53.8%) | 3/5 (60%) | 7/11 (63.6%) | 11/28 (39.3%) | 25/47 (53.2%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 2/13 (15.4%) | 3/13 (23.1%) | 2/5 (40%) | 0/11 (0%) | 1/28 (3.6%) | 8/47 (17%) | ||||||
| Disseminated intravascular coagulation | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Haemorrhagic anaemia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Leukopenia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Neutropenia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Pancytopenia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Thrombocytopenia | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Cardiac disorders | ||||||||||||
| Acute coronary syndrome | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Angina pectoris | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Cardiac failure | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Right ventricular failure | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| Ascites | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Diarrhoea | 1/13 (7.7%) | 0/13 (0%) | 1/5 (20%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Gastritis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Gastritis haemorrhagic | 0/13 (0%) | 1/13 (7.7%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gastrointestinal haemorrhage | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| Intestinal obstruction | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Mallory-Weiss syndrome | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Melaena | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 4/47 (8.5%) | ||||||
| Nausea | 0/13 (0%) | 0/13 (0%) | 2/5 (40%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Peritoneal haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Rectal haemorrhage | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Small intestinal obstruction | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Vomiting | 1/13 (7.7%) | 0/13 (0%) | 2/5 (40%) | 0/11 (0%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| General disorders | ||||||||||||
| Asthenia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Catheter related complication | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Disease progression | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 3/47 (6.4%) | ||||||
| Drug interaction | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Fatigue | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| General physical health deterioration | 1/13 (7.7%) | 1/13 (7.7%) | 2/5 (40%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Malaise | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Mucosal haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Multi-organ failure | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Oedema peripheral | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Pain | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pyrexia | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Ulcer haemorrhage | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Cholestasis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Hepatic failure | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Hepatosplenomegaly | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Abdominal abscess | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Bronchitis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Bronchopneumonia | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gastroenteritis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Herpes zoster | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Lung infection | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Morganella infection | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pneumocystis jiroveci pneumonia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pneumonia | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Sepsis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Septic shock | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Urinary tract infection | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Post procedural haemorrhage | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Investigations | ||||||||||||
| Blood bilirubin increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Blood creatinine increased | 4/13 (30.8%) | 2/13 (15.4%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Blood lactate dehydrogenase increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Blood potassium increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Blood uric acid increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Haemoglobin decreased | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Dehydration | 1/13 (7.7%) | 1/13 (7.7%) | 1/5 (20%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Hypoglycaemia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Hypokalaemia | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Hyponatraemia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Intervertebral disc protrusion | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Gastrointestinal stromal tumour | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Metastases to peritoneum | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Tumour haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Tumour lysis syndrome | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Tumour pain | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Tumour ulceration | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Convulsion | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hepatic encephalopathy | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Neuropathy peripheral | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Psychiatric disorders | ||||||||||||
| Confusional state | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Mental status changes | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Costovertebral angle tenderness | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Renal failure | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Renal failure acute | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Ureteric obstruction | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Urethral stenosis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Reproductive system and breast disorders | ||||||||||||
| Pelvic discomfort | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Dyspnoea | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 3/47 (6.4%) | ||||||
| Pleural effusion | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Pulmonary embolism | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Pulmonary hypertension | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Respiratory failure | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Angioedema | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Dry skin | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Swelling face | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Haemodynamic instability | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hypovolaemic shock | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Shock | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Venous thrombosis limb | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| Phase I - RAD001 20mg/Week ++ Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 600mg/Day | Phase I: RAD001 5mg/Day + Glivec 600mg/Day | Phase I: RAD001 2.5mg/Day + Glivec 800mg/Day | Phase ll - Stratum l (First-line Resistant/Refractory): RAD001 2.5mg/Day + Glivec 600mg/Day | Phase ll: Stratum ll (Post Second-line Therapy) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/13 (100%) | 12/13 (92.3%) | 5/5 (100%) | 11/11 (100%) | 27/28 (96.4%) | 47/47 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 6/13 (46.2%) | 7/13 (53.8%) | 3/5 (60%) | 4/11 (36.4%) | 12/28 (42.9%) | 22/47 (46.8%) | ||||||
| Anaemia of malignant disease | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 2/28 (7.1%) | 0/47 (0%) | ||||||
| Leukopenia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 3/11 (27.3%) | 5/28 (17.9%) | 3/47 (6.4%) | ||||||
| Lymphadenopathy | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 0/47 (0%) | ||||||
| Lymphopenia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 2/28 (7.1%) | 0/47 (0%) | ||||||
| Neutropenia | 1/13 (7.7%) | 0/13 (0%) | 2/5 (40%) | 0/11 (0%) | 5/28 (17.9%) | 5/47 (10.6%) | ||||||
| Thrombocytopenia | 0/13 (0%) | 3/13 (23.1%) | 2/5 (40%) | 2/11 (18.2%) | 4/28 (14.3%) | 7/47 (14.9%) | ||||||
| Cardiac disorders | ||||||||||||
| Coronary artery disease | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Cyanosis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Mitral valve incompetence | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Ear and labyrinth disorders | ||||||||||||
| Ear pain | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Vertigo | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Endocrine disorders | ||||||||||||
| Hyperthyroidism | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Eye disorders | ||||||||||||
| Conjunctival haemorrhage | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Conjunctivitis | 0/13 (0%) | 2/13 (15.4%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 6/47 (12.8%) | ||||||
| Eye oedema | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Eye swelling | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 1/47 (2.1%) | ||||||
| Eyelid oedema | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 4/11 (36.4%) | 4/28 (14.3%) | 8/47 (17%) | ||||||
| Lacrimation increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Orbital oedema | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal discomfort | 1/13 (7.7%) | 2/13 (15.4%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| Abdominal distension | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Abdominal pain | 3/13 (23.1%) | 5/13 (38.5%) | 2/5 (40%) | 3/11 (27.3%) | 11/28 (39.3%) | 12/47 (25.5%) | ||||||
| Abdominal pain lower | 2/13 (15.4%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Abdominal pain upper | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 2/28 (7.1%) | 5/47 (10.6%) | ||||||
| Anal haemorrhage | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Ascites | 0/13 (0%) | 1/13 (7.7%) | 1/5 (20%) | 1/11 (9.1%) | 0/28 (0%) | 2/47 (4.3%) | ||||||
| Cheilitis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Constipation | 4/13 (30.8%) | 2/13 (15.4%) | 2/5 (40%) | 1/11 (9.1%) | 5/28 (17.9%) | 7/47 (14.9%) | ||||||
| Diarrhoea | 8/13 (61.5%) | 5/13 (38.5%) | 2/5 (40%) | 7/11 (63.6%) | 12/28 (42.9%) | 17/47 (36.2%) | ||||||
| Diarrhoea haemorrhagic | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 2/47 (4.3%) | ||||||
| Dry mouth | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 2/47 (4.3%) | ||||||
| Dyspepsia | 1/13 (7.7%) | 1/13 (7.7%) | 0/5 (0%) | 3/11 (27.3%) | 2/28 (7.1%) | 3/47 (6.4%) | ||||||
| Dysphagia | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Flatulence | 1/13 (7.7%) | 2/13 (15.4%) | 0/5 (0%) | 3/11 (27.3%) | 6/28 (21.4%) | 1/47 (2.1%) | ||||||
| Gastritis | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gastrointestinal haemorrhage | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gastrointestinal pain | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gastrooesophageal reflux disease | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 2/47 (4.3%) | ||||||
| Haemorrhoids | 1/13 (7.7%) | 2/13 (15.4%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 3/47 (6.4%) | ||||||
| Lip oedema | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Melaena | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Nausea | 7/13 (53.8%) | 8/13 (61.5%) | 5/5 (100%) | 7/11 (63.6%) | 12/28 (42.9%) | 16/47 (34%) | ||||||
| Oesophagitis | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Painful defaecation | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Reflux oesophagitis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Retching | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Stomatitis | 3/13 (23.1%) | 2/13 (15.4%) | 1/5 (20%) | 3/11 (27.3%) | 4/28 (14.3%) | 7/47 (14.9%) | ||||||
| Vomiting | 3/13 (23.1%) | 3/13 (23.1%) | 3/5 (60%) | 5/11 (45.5%) | 6/28 (21.4%) | 14/47 (29.8%) | ||||||
| General disorders | ||||||||||||
| Asthenia | 1/13 (7.7%) | 3/13 (23.1%) | 0/5 (0%) | 0/11 (0%) | 5/28 (17.9%) | 7/47 (14.9%) | ||||||
| Chest pain | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 4/47 (8.5%) | ||||||
| Chills | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| Face oedema | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 1/11 (9.1%) | 2/28 (7.1%) | 3/47 (6.4%) | ||||||
| Fatigue | 9/13 (69.2%) | 8/13 (61.5%) | 2/5 (40%) | 9/11 (81.8%) | 15/28 (53.6%) | 16/47 (34%) | ||||||
| Feeling cold | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 3/47 (6.4%) | ||||||
| General physical health deterioration | 1/13 (7.7%) | 0/13 (0%) | 2/5 (40%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Localised oedema | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 2/47 (4.3%) | ||||||
| Malaise | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Mucosal inflammation | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 2/11 (18.2%) | 0/28 (0%) | 6/47 (12.8%) | ||||||
| Non-cardiac chest pain | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Oedema | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 4/28 (14.3%) | 5/47 (10.6%) | ||||||
| Oedema peripheral | 2/13 (15.4%) | 2/13 (15.4%) | 1/5 (20%) | 8/11 (72.7%) | 8/28 (28.6%) | 17/47 (36.2%) | ||||||
| Pain | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pitting oedema | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Pyrexia | 3/13 (23.1%) | 5/13 (38.5%) | 3/5 (60%) | 3/11 (27.3%) | 4/28 (14.3%) | 9/47 (19.1%) | ||||||
| Temperature intolerance | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 2/47 (4.3%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Cholelithiasis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hepatic pain | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Bronchitis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 2/28 (7.1%) | 4/47 (8.5%) | ||||||
| Campylobacter infection | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Candidiasis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Conjunctivitis infective | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gastroenteritis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| Genital infection fungal | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Helicobacter infection | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Infection | 1/13 (7.7%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Lung infection | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Nasopharyngitis | 1/13 (7.7%) | 1/13 (7.7%) | 0/5 (0%) | 4/11 (36.4%) | 3/28 (10.7%) | 1/47 (2.1%) | ||||||
| Oral candidiasis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Oral herpes | 0/13 (0%) | 1/13 (7.7%) | 1/5 (20%) | 0/11 (0%) | 1/28 (3.6%) | 3/47 (6.4%) | ||||||
| Pharyngitis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Pneumonia | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Respiratory tract infection | 1/13 (7.7%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Sepsis | 2/13 (15.4%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Tooth abscess | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Tooth infection | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Upper respiratory tract infection | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Urinary tract infection | 1/13 (7.7%) | 1/13 (7.7%) | 2/5 (40%) | 2/11 (18.2%) | 1/28 (3.6%) | 3/47 (6.4%) | ||||||
| Urinary tract infection bacterial | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Viral infection | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Excoriation | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Fall | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Head injury | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Muscle strain | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Procedural pain | 4/13 (30.8%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 4/28 (14.3%) | 2/47 (4.3%) | ||||||
| Investigations | ||||||||||||
| Alanine aminotransferase increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Aspartate aminotransferase increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Blood alkaline phosphatase increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 0/47 (0%) | ||||||
| Blood bilirubin increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Blood creatinine increased | 1/13 (7.7%) | 0/13 (0%) | 1/5 (20%) | 1/11 (9.1%) | 2/28 (7.1%) | 2/47 (4.3%) | ||||||
| Creatinine renal clearance decreased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Haemoglobin increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Transaminases increased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Weight decreased | 4/13 (30.8%) | 3/13 (23.1%) | 3/5 (60%) | 2/11 (18.2%) | 6/28 (21.4%) | 8/47 (17%) | ||||||
| Weight increased | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Anorexia | 4/13 (30.8%) | 5/13 (38.5%) | 2/5 (40%) | 5/11 (45.5%) | 6/28 (21.4%) | 16/47 (34%) | ||||||
| Electrolyte imbalance | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Fluid retention | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hyperkalaemia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/28 (0%) | 2/47 (4.3%) | ||||||
| Hypertriglyceridaemia | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hyperuricaemia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 2/47 (4.3%) | ||||||
| Hypoalbuminaemia | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 1/28 (3.6%) | 2/47 (4.3%) | ||||||
| Hypocalcaemia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 4/47 (8.5%) | ||||||
| Hypokalaemia | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 5/11 (45.5%) | 5/28 (17.9%) | 11/47 (23.4%) | ||||||
| Hypomagnesaemia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hypovitaminosis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Iron deficiency | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Magnesium deficiency | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Tetany | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Arthritis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Back pain | 2/13 (15.4%) | 2/13 (15.4%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Flank pain | 1/13 (7.7%) | 1/13 (7.7%) | 1/5 (20%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Gouty arthritis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Mastication disorder | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Muscle spasms | 3/13 (23.1%) | 1/13 (7.7%) | 1/5 (20%) | 0/11 (0%) | 4/28 (14.3%) | 5/47 (10.6%) | ||||||
| Musculoskeletal chest pain | 1/13 (7.7%) | 1/13 (7.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Musculoskeletal stiffness | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Myalgia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 3/11 (27.3%) | 1/28 (3.6%) | 4/47 (8.5%) | ||||||
| Neck pain | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Pain in extremity | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 1/11 (9.1%) | 1/28 (3.6%) | 4/47 (8.5%) | ||||||
| Trismus | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Metastases to liver | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Tumour pain | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 1/47 (2.1%) | ||||||
| Nervous system disorders | ||||||||||||
| Ageusia | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Dizziness | 2/13 (15.4%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Dysgeusia | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 1/11 (9.1%) | 4/28 (14.3%) | 2/47 (4.3%) | ||||||
| Headache | 4/13 (30.8%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 8/28 (28.6%) | 6/47 (12.8%) | ||||||
| Hyposmia | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Peripheral motor neuropathy | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Peripheral sensory neuropathy | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Sinus headache | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Psychiatric disorders | ||||||||||||
| Anxiety | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Depression | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 5/47 (10.6%) | ||||||
| Distractibility | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Insomnia | 3/13 (23.1%) | 1/13 (7.7%) | 3/5 (60%) | 2/11 (18.2%) | 1/28 (3.6%) | 3/47 (6.4%) | ||||||
| Nervousness | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Restlessness | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Sleep disorder | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 2/11 (18.2%) | 3/28 (10.7%) | 1/47 (2.1%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Bladder spasm | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Dysuria | 1/13 (7.7%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Haematuria | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 2/28 (7.1%) | 1/47 (2.1%) | ||||||
| Micturition frequency decreased | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Micturition urgency | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pollakiuria | 2/13 (15.4%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Reproductive system and breast disorders | ||||||||||||
| Nipple pain | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Oedema genital | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Paraesthesia of genital male | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Pelvic discomfort | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Prostatic intraepithelial neoplasia | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Scrotal oedema | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 2/13 (15.4%) | 6/13 (46.2%) | 1/5 (20%) | 2/11 (18.2%) | 3/28 (10.7%) | 7/47 (14.9%) | ||||||
| Dyspnoea | 2/13 (15.4%) | 3/13 (23.1%) | 0/5 (0%) | 2/11 (18.2%) | 1/28 (3.6%) | 6/47 (12.8%) | ||||||
| Dyspnoea exertional | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 3/28 (10.7%) | 2/47 (4.3%) | ||||||
| Epistaxis | 0/13 (0%) | 1/13 (7.7%) | 1/5 (20%) | 2/11 (18.2%) | 2/28 (7.1%) | 5/47 (10.6%) | ||||||
| Lung infiltration | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Nasal congestion | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Nasal discomfort | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Pharyngolaryngeal pain | 0/13 (0%) | 2/13 (15.4%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pleural effusion | 1/13 (7.7%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 1/28 (3.6%) | 1/47 (2.1%) | ||||||
| Pleuritic pain | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pulmonary hypertension | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Rales | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Rhinorrhoea | 2/13 (15.4%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Acne | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Angioedema | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Dermatitis | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Dermatitis contact | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Dermatosis | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Dry skin | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 2/28 (7.1%) | 6/47 (12.8%) | ||||||
| Ecchymosis | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Eczema | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 0/47 (0%) | ||||||
| Erythema | 1/13 (7.7%) | 0/13 (0%) | 2/5 (40%) | 1/11 (9.1%) | 2/28 (7.1%) | 1/47 (2.1%) | ||||||
| Hyperhidrosis | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Hypoaesthesia facial | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Night sweats | 1/13 (7.7%) | 0/13 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/28 (3.6%) | 3/47 (6.4%) | ||||||
| Onychoclasis | 0/13 (0%) | 2/13 (15.4%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Periorbital oedema | 2/13 (15.4%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 2/28 (7.1%) | 4/47 (8.5%) | ||||||
| Petechiae | 0/13 (0%) | 0/13 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/28 (0%) | 1/47 (2.1%) | ||||||
| Pruritus | 1/13 (7.7%) | 0/13 (0%) | 1/5 (20%) | 0/11 (0%) | 2/28 (7.1%) | 1/47 (2.1%) | ||||||
| Rash | 4/13 (30.8%) | 1/13 (7.7%) | 1/5 (20%) | 2/11 (18.2%) | 5/28 (17.9%) | 13/47 (27.7%) | ||||||
| Rash macular | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Skin fragility | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 2/11 (18.2%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Skin irritation | 0/13 (0%) | 1/13 (7.7%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Swelling face | 0/13 (0%) | 0/13 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/28 (0%) | 0/47 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Hypertension | 2/13 (15.4%) | 0/13 (0%) | 0/5 (0%) | 0/11 (0%) | 0/28 (0%) | 0/47 (0%) | ||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01275222
Other Study ID Numbers:
- CRAD001C2206
First Posted:
Jan 12, 2011
Last Update Posted:
Jun 25, 2021
Last Verified:
Jun 1, 2021