CCFZ533X2201 - PoC Study in de Novo Renal Transplantation
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02217410
Collaborator
(none)
59
14
3
33.8
4.2
0.1
Study Details
Study Description
Brief Summary
The purpose of this study was to investigate the safety, tolerability, pharmacokinetics (PK) and potential for CFZ533 to replace calcineurin inhibitors (CNI), while providing a similar rate of acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
59 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A 12-month Randomized, Multiple Dose, Open-label, Study Evaluating Safety, Tolerability, Pharmacokinetics/Pharmacodynamics (PK/PD) and Efficacy of an Anti-CD40 Monoclonal Antibody, CFZ533, in Combination With Mycophenolate Mofetil (MMF) and Corticosteroids (CS), With and Without Tacrolimus (Tac), in de Novo Renal Transplant Recipients
Actual Study Start Date
:
Feb 5, 2015
Actual Primary Completion Date
:
Nov 29, 2017
Actual Study Completion Date
:
Nov 29, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regimen A CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). |
Biological: CFZ533
Drug: Tacrolimus (Tac)
Drug: Mycophenolate mofetil (MMF)
Drug: Corticosteroids (CS)
|
| Experimental: Regimen B CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction |
Biological: CFZ533
Drug: Mycophenolate mofetil (MMF)
Drug: Corticosteroids (CS)
Biological: anti-IL2 Induction
|
| Active Comparator: Regimen C Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] |
Drug: Tacrolimus (Tac)
Drug: Mycophenolate mofetil (MMF)
Drug: Corticosteroids (CS)
Biological: anti-IL2 Induction
|
Outcome Measures
Primary Outcome Measures
- Mean Cmax Pharmacokinetic Parameter- Part I [Day 1]
Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I
- Mean Tmax Pharmacokinetic Parameter - Part I [Day 1]
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
- Mean AUClast Pharmacokinetic Parameter - Part I [Day 1]
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
- Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II [3, 6, 9, and 12 months]
To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy.
Secondary Outcome Measures
- Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 [Baseline to end of study (Day 1, Day 29, Day 337)]
To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154
- Free CD40 and Total CD40 on B Cells - Part II [Baseline to end of study (Day 1/predose)]
The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome
- Anti-CFZ533 Antibodies - Part I [Baseline to end of study]
To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies
- Anti-CFZ533 Antibodies - Part II [Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)]
To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies
- eGFR - Part II [Day 1, Day 29, Day 337,]
Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula. eGFR: Estimated glomerular filtration rate
- CFZ533 Plasma PK Concentrations - Part II [throughout study period (day 84 to day 336)]
Quantify the systemic concentrations of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. A full pharmacokinetic analysis can be performed on the concentration-time data to evaluate the impact of renal transplantation on the various medications used in the treatment regimen.
- Total sCD40 Plasma Concentrations - Part II [12 months]
To quantify the change from baseline and recovery of peripheral blood total soluble CD40
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Main Inclusion Criteria:
-
Written informed consent must be obtained before any assessment is performed.
-
Recipients of a kidney transplant from a heart-beating deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor.
-
Recipients of a kidney with a cold ischemia time (CIT) < 30 hours.
Main Exclusion Criteria:
-
Recipients of an organ from a non-heart beating donor.
-
ABO incompatible or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
-
Subjects receiving a second kidney allograft, unless the first allograft was lost due to surgical complication.
-
Subjects at high immunological risk for rejection
-
Subjects at risk for tuberculosis (TB)
-
Subject with severe systemic infections, current or within the two weeks prior to randomization/enrollment.
-
Any additional contraindication to the use of tacrolimus or mycophenolate mofetil according to the national labeling information of these products (see local product label).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Aurora | Colorado | United States | 80045 |
| 2 | Novartis Investigative Site | Baltimore | Maryland | United States | 21201 |
| 3 | Novartis Investigative Site | Ann Arbor | Michigan | United States | 48109 5271 |
| 4 | Novartis Investigative Site | Detroit | Michigan | United States | 48202 |
| 5 | Novartis Investigative Site | Livingston | New Jersey | United States | 07039 |
| 6 | Novartis Investigative Site | Cincinnati | Ohio | United States | 45267-0585 |
| 7 | Novartis Investigative Site | São Paulo | SP | Brazil | 04038-002 |
| 8 | Novartis Investigative Site | Berlin | Germany | D-13353 | |
| 9 | Novartis Investigative Site | Essen | Germany | 45147 | |
| 10 | Novartis Investigative Site | Hamburg | Germany | 20246 | |
| 11 | Novartis Investigative Site | Heidelberg | Germany | 69120 | |
| 12 | Novartis Investigative Site | Utrecht | The Netherlands | Netherlands | 3508 GA |
| 13 | Novartis Investigative Site | Groningen | Netherlands | 9713 GZ | |
| 14 | Novartis Investigative Site | Rotterdam | Netherlands | 3000 CA |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02217410
Other Study ID Numbers:
- CCFZ533X2201
First Posted:
Aug 15, 2014
Last Update Posted:
Sep 28, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | In Part 1, patients were enrolled into Arm 1. In Part 2, patients were randomized (2:1) to Arms 2A and 2B. |
|---|---|
| Pre-assignment Detail | Study Part 1 focused on measuring the multiple-dose safety, tolerability, PK, and PD of both IV and SC CFZ533 when administered with the SoC treatment regimen. Study Part 2 investigated efficacy, safety, tolerability, PK and PD of CFZ533 in the absence of Tac. |
| Arm/Group Title | CFZ533 + TAC + MMF (Part 1) | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) |
|---|---|---|---|
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] |
| Period Title: Overall Study | |||
| STARTED | 7 | 34 | 18 |
| COMPLETED | 6 | 30 | 13 |
| NOT COMPLETED | 1 | 4 | 5 |
Baseline Characteristics
| Arm/Group Title | CFZ533 + TAC + MMF (Part 1) | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) | Total |
|---|---|---|---|---|
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] | Total of all reporting groups |
| Overall Participants | 7 | 34 | 18 | 59 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
48.1
(9.30)
|
49.0
(15.79)
|
53.4
(18.01)
|
50.1
(15.91)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
42.9%
|
8
23.5%
|
6
33.3%
|
17
28.8%
|
| Male |
4
57.1%
|
26
76.5%
|
12
66.7%
|
42
71.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
1
2.9%
|
0
0%
|
1
1.7%
|
| Not Hispanic or Latino |
2
28.6%
|
20
58.8%
|
9
50%
|
31
52.5%
|
| Unknown or Not Reported |
5
71.4%
|
13
38.2%
|
9
50%
|
27
45.8%
|
Outcome Measures
| Title | Mean Cmax Pharmacokinetic Parameter- Part I |
|---|---|
| Description | Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Analysis Set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | CFZ533 + TAC + MMF (Part 1) |
|---|---|
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). |
| Measure Participants | 7 |
| Mean (Standard Deviation) [ug/mL] |
66.3
(12.3)
|
| Title | Mean Tmax Pharmacokinetic Parameter - Part I |
|---|---|
| Description | Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Analysis Set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | CFZ533 + TAC + MMF (Part 1) |
|---|---|
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). |
| Measure Participants | 7 |
| Median (Full Range) [day] |
0.237
|
| Title | Mean AUClast Pharmacokinetic Parameter - Part I |
|---|---|
| Description | Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Analysis Set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | CFZ533 + TAC + MMF (Part 1) |
|---|---|
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). |
| Measure Participants | 7 |
| Mean (Standard Deviation) [day*ug/mL] |
367
(52.0)
|
| Title | Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II |
|---|---|
| Description | To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy. |
| Time Frame | 3, 6, 9, and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data. |
| Arm/Group Title | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) |
|---|---|---|
| Arm/Group Description | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] |
| Measure Participants | 33 | 18 |
| Month 3 |
6
|
2
|
| Month 6 |
7
|
3
|
| Month 9 |
7
|
3
|
| Month 12 |
7
|
3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CFZ533 + TAC + MMF (Part 1), Tac + MMF (Part 2) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8976 |
| Comments | ||
| Method | Bayesian posterior probability | |
| Comments | Posterior probability that the composite efficacy failure difference between CFZ533 and Tac is < 20%. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.095 | |
| Confidence Interval |
(2-Sided) 95% -0.067 to 0.263 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Month 3 | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | CFZ533 + TAC + MMF (Part 1), Tac + MMF (Part 2) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8836 |
| Comments | ||
| Method | Bayesian posterior probability | |
| Comments | Posterior probability that the composite efficacy failure difference between CFZ533 and Tac is < 20%. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.093 | |
| Confidence Interval |
(2-Sided) 95% -0.084 to 0.271 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Month 6 | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | CFZ533 + TAC + MMF (Part 1), Tac + MMF (Part 2) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8822 |
| Comments | ||
| Method | Bayesian posterior probability | |
| Comments | Posterior probability that the composite efficacy failure difference between CFZ533 and Tac is < 20%. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.093 | |
| Confidence Interval |
(2-Sided) 95% -0.085 to 0.272 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Month 9 | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | CFZ533 + TAC + MMF (Part 1), Tac + MMF (Part 2) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8821 |
| Comments | ||
| Method | Bayesian posterior probability | |
| Comments | Posterior probability that the composite efficacy failure difference between CFZ533 and Tac is < 20%. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.093 | |
| Confidence Interval |
(2-Sided) 95% -0.087 to 0.273 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Month 12 | |
| Title | Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 |
|---|---|
| Description | To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154 |
| Time Frame | Baseline to end of study (Day 1, Day 29, Day 337) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data. |
| Arm/Group Title | sCD40 (Part I) | sCD154 |
|---|---|---|
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). |
| Measure Participants | 7 | 7 |
| Baseline |
4.03
(4.08)
|
0.125
(0.007)
|
| Day 1 |
8.86
(0.0585)
|
0.0585
(0.0711)
|
| Day 2 |
16.7
(4.51)
|
0.139
(0.193)
|
| Day 3 |
24.8
(4.47)
|
0.157
(0.235)
|
| Day 4 |
31.3
(6.34)
|
0.241
(0.418)
|
| Day 8 |
54.0
(11.2)
|
0.399
(0.636)
|
| Day 15 |
84.1
(13.8)
|
0.0879
(0.139)
|
| Day 22 |
102
(13.9)
|
0.0500
(0.132)
|
| Day 29 |
120
(15.7)
|
0.225
(0.504)
|
| Day 36 |
128
(19.2)
|
0.116
(0.2)
|
| Day 43 |
145
(25.6)
|
0.0193
(0.0474)
|
| Day 50 |
156
(6.35)
|
0.0478
(0.0687)
|
| Day 57 |
161
(21.2)
|
0
(0)
|
| Day 64 |
163
(24.2)
|
0.0316
(0.0492)
|
| Day 71 |
156
(19.2)
|
0.0148
(0.0363)
|
| Day 85 |
168
(21.4)
|
0.0139
(0.0340)
|
| Day 99 |
155
(23.3)
|
0
(0)
|
| Day 113 |
85.7
(47.9)
|
0.0668
(0.164)
|
| Day 127 |
12.2
(15.7)
|
0.0488
(0.0697)
|
| EoS |
0.918
(0.330)
|
0.0184
(0.0411)
|
| Title | Free CD40 and Total CD40 on B Cells - Part II |
|---|---|
| Description | The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome |
| Time Frame | Baseline to end of study (Day 1/predose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data. |
| Arm/Group Title | Free CD40 on Whole Blood B Ceels | Total CD40 on Whole Blood B Cells |
|---|---|---|
| Arm/Group Description | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction |
| Measure Participants | 26 | 29 |
| CFZ553 + MMF (Baseline) |
30836.00
(13648.69)
|
12778.80
(7873.76)
|
| CFZ553 + MMF (D1 - 6h post dose) |
1623.81
(1359.85)
|
13806.90
(7185.66)
|
| CFZ553 + MMF (D15) |
799.62
(762.38)
|
15160.38
(7398.57)
|
| CFZ553 + MMF (D 29) |
817.63
(1540.16)
|
13299.60
(6330.89)
|
| CFZ553 + MMF (D 57) |
597.13
(523.55)
|
12234.38
(6943.13)
|
| CFZ553 + MMF (D 85) |
635.47
(614.68)
|
9330.86
(8484.46)
|
| CFZ553 + MMF (D 197) |
3699.0
(7298.98)
|
2820.72
(2347.11)
|
| CFZ553 + MMF (253) |
2667.38
(6146.86)
|
1427.14
(740.48)
|
| CFZ553 + MMF (EoS) |
176.17
(266.82)
|
1069.67
(809.12)
|
| Tac + MMF (Baseline) |
31508.33
(12759.49)
|
14581.43
(9342.79)
|
| Tac + MMF (D1 - 6h post dose) |
26437.65
(11930.50)
|
13715.00
(8293.33)
|
| Tac + MMF (D15) |
24441.67
(9125.93)
|
13707.14
(6770.14)
|
| Tac + MMF (D29) |
27840.00
(12106.72)
|
12698.75
(6002.96)
|
| Tac + MMF (D57) |
27994.29
(12004.57)
|
12583.85
(6210.07)
|
| Tac + MMF (D85) |
25044.00
(10896.65)
|
8701.54
(4183.00)
|
| Tac + MMF (D197) |
21360.00
(3155.67)
|
2067.60
(1617.28)
|
| Tac + MMF (D253) |
15752.75
(7145.32)
|
1750.50
(1005.84)
|
| Tac + MMF (EoS) |
21200.00
(4407.95)
|
6276.17
(11271.20)
|
| Title | Anti-CFZ533 Antibodies - Part I |
|---|---|
| Description | To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies |
| Time Frame | Baseline to end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all patients that received at least one dose of study drug. |
| Arm/Group Title | CFZ533 + TAC + MMF (Part 1) |
|---|---|
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). |
| Measure Participants | 7 |
| Number [anti-CFZ533 antibodies] |
0
|
| Title | Anti-CFZ533 Antibodies - Part II |
|---|---|
| Description | To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies |
| Time Frame | Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all patients that received at least one dose of study drug. For Part 2, all patients that received their transplant along with any patient who received study drug but had no transplant were combined. |
| Arm/Group Title | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) |
|---|---|---|
| Arm/Group Description | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] |
| Measure Participants | 34 | 18 |
| Screening |
0
|
0
|
| Baseline |
0
|
|
| Day 141 |
0
|
0
|
| Day 225 |
0
|
0
|
| Day 309 |
0
|
0
|
| Study Completion |
0
|
0
|
| Title | eGFR - Part II |
|---|---|
| Description | Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula. eGFR: Estimated glomerular filtration rate |
| Time Frame | Day 1, Day 29, Day 337, |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all patients that received at least one dose of study drug. For Part 2, all patients that received their transplant along with any patient who received study drug but had no transplant were combined. |
| Arm/Group Title | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) |
|---|---|---|
| Arm/Group Description | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] |
| Measure Participants | 32 | 18 |
| Day 1 |
9.8
|
9.7
|
| Day 29 |
55.6
|
44.3
|
| Day 337 |
58.2
|
44.2
|
| Title | CFZ533 Plasma PK Concentrations - Part II |
|---|---|
| Description | Quantify the systemic concentrations of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. A full pharmacokinetic analysis can be performed on the concentration-time data to evaluate the impact of renal transplantation on the various medications used in the treatment regimen. |
| Time Frame | throughout study period (day 84 to day 336) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Analysis Set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | CFZ533 + MMF (Part 2) |
|---|---|
| Arm/Group Description | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction |
| Measure Participants | 32 |
| Day 84 |
247
(58.2)
|
| Day 112 |
211
(51.8)
|
| Day 140 |
178
(54.9)
|
| Day 168 |
157
(57.4)
|
| Day 196 |
148
(53.1)
|
| Day 224 |
147
(53.8)
|
| Day 252 |
151
(35.2)
|
| Day 280 |
160
(87.7)
|
| Day 308 |
132
(42.5)
|
| Day 336 |
156
(85.2)
|
| End of study |
133
(57.8)
|
| Title | Total sCD40 Plasma Concentrations - Part II |
|---|---|
| Description | To quantify the change from baseline and recovery of peripheral blood total soluble CD40 |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data. |
| Arm/Group Title | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) |
|---|---|---|
| Arm/Group Description | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] |
| Measure Participants | 32 | 17 |
| Baseline |
3.02
(2.44)
|
3.67
(2.15)
|
| Day 1 |
6.95
(4.29)
|
1.16
(1.15)
|
| Day 4 |
24.6
(11.0)
|
1.16
(1.15)
|
| Day 15 |
69.6
(21.5)
|
0.869
(1.55)
|
| Day 29 |
101
(18.9)
|
0.362
(0.0746)
|
| Day 57 |
140
(17.4)
|
0.438
(0.316)
|
| Day 85 |
189
(76.4)
|
0.429
(0.324)
|
| Day 113 |
215
(75.5)
|
0.391
(0.129)
|
| Day 141 |
237
(93.1)
|
0.453
(0.271)
|
| Day 169 |
238
(80.3)
|
0.537
(0.215)
|
| Day 197 |
253
(81.3)
|
0.423
(0.0908)
|
| Day 225 |
258
(77.7)
|
0.452
(0.119)
|
| Day 253 |
236
(36.5)
|
0.457
(0.0800)
|
| Day 281 |
273
(71.3)
|
0.455
(0.0789)
|
| Day 309 |
286
(66.0)
|
0.454
(0.0957)
|
| Day 337 |
298
(57.4)
|
0.411
(0.0581)
|
| End of Study |
303
(59.7)
|
0.959
(1.88)
|
Adverse Events
| Time Frame | Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | CFZ533 + TAC + MMF (Part 1) | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) | Total | ||||
| Arm/Group Description | CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] | Total | ||||
All Cause Mortality |
||||||||
| CFZ533 + TAC + MMF (Part 1) | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/34 (0%) | 0/18 (0%) | 0/59 (0%) | ||||
Serious Adverse Events |
||||||||
| CFZ533 + TAC + MMF (Part 1) | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/7 (57.1%) | 21/34 (61.8%) | 12/18 (66.7%) | 37/59 (62.7%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Leukopenia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Pancytopenia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Tricuspid valve incompetence | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Eye disorders | ||||||||
| Photophobia | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Vision blurred | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Diarrhoea | 1/7 (14.3%) | 1/34 (2.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Diarrhoea haemorrhagic | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gastrointestinal inflammation | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Inguinal hernia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Mouth ulceration | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Nausea | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pancreatitis | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Retroperitoneal haematoma | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Vomiting | 2/7 (28.6%) | 0/34 (0%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Immune system disorders | ||||||||
| Kidney transplant rejection | 0/7 (0%) | 5/34 (14.7%) | 1/18 (5.6%) | 6/59 (10.2%) | ||||
| Transplant rejection | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Cytomegalovirus infection | 0/7 (0%) | 3/34 (8.8%) | 2/18 (11.1%) | 5/59 (8.5%) | ||||
| Encephalitis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Enterobacter bacteraemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gastroenteritis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gastrointestinal infection | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Hepatitis C | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pneumocystis jirovecii pneumonia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Polyomavirus-associated nephropathy | 0/7 (0%) | 4/34 (11.8%) | 1/18 (5.6%) | 5/59 (8.5%) | ||||
| Pyelonephritis | 0/7 (0%) | 2/34 (5.9%) | 3/18 (16.7%) | 5/59 (8.5%) | ||||
| Renal cyst infection | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Urosepsis | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arteriovenous fistula aneurysm | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Complications of transplanted kidney | 1/7 (14.3%) | 1/34 (2.9%) | 2/18 (11.1%) | 4/59 (6.8%) | ||||
| Delayed graft function | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Graft loss | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Incarcerated incisional hernia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Incisional hernia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Transplant dysfunction | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Transplant failure | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Investigations | ||||||||
| Amylase increased | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Blood creatinine increased | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| White blood cell count decreased | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hyperglycaemia | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hyperkalaemia | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Basosquamous carcinoma | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Squamous cell carcinoma | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Nervous system disorders | ||||||||
| Headache | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Psychiatric disorders | ||||||||
| Mental status changes | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Renal tubular necrosis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Urinary retention | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pneumothorax | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pulmonary embolism | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hypertension | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hypertensive crisis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Lymphocele | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Pelvic venous thrombosis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| CFZ533 + TAC + MMF (Part 1) | CFZ533 + MMF (Part 2) | Tac + MMF (Part 2) | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 33/34 (97.1%) | 18/18 (100%) | 58/59 (98.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/7 (14.3%) | 3/34 (8.8%) | 4/18 (22.2%) | 8/59 (13.6%) | ||||
| Iron deficiency anaemia | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Leukocytosis | 1/7 (14.3%) | 3/34 (8.8%) | 2/18 (11.1%) | 6/59 (10.2%) | ||||
| Leukopenia | 1/7 (14.3%) | 13/34 (38.2%) | 3/18 (16.7%) | 17/59 (28.8%) | ||||
| Lymphopenia | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Microcytic anaemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Nephrogenic anaemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Neutropenia | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Normocytic anaemia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Pancytopenia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Polycythaemia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Thrombocytopenia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Thrombocytosis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Arrhythmia | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Atrial fibrillation | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Bradycardia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Extrasystoles | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Myocardial infarction | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Palpitations | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Sinus tachycardia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Tachycardia | 2/7 (28.6%) | 4/34 (11.8%) | 1/18 (5.6%) | 7/59 (11.9%) | ||||
| Tricuspid valve incompetence | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| Hydrocele | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear discomfort | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Vertigo | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Endocrine disorders | ||||||||
| Hyperparathyroidism | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hyperparathyroidism secondary | 2/7 (28.6%) | 0/34 (0%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Eye disorders | ||||||||
| Chalazion | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Dry eye | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Eye movement disorder | 2/7 (28.6%) | 0/34 (0%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Ocular hyperaemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Retinal vein occlusion | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Abdominal distension | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Abdominal pain | 1/7 (14.3%) | 3/34 (8.8%) | 3/18 (16.7%) | 7/59 (11.9%) | ||||
| Abdominal pain lower | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Abdominal pain upper | 0/7 (0%) | 5/34 (14.7%) | 0/18 (0%) | 5/59 (8.5%) | ||||
| Anal fissure | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Aphthous ulcer | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Colitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Constipation | 1/7 (14.3%) | 14/34 (41.2%) | 8/18 (44.4%) | 23/59 (39%) | ||||
| Diarrhoea | 2/7 (28.6%) | 8/34 (23.5%) | 10/18 (55.6%) | 20/59 (33.9%) | ||||
| Duodenogastric reflux | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Dyspepsia | 2/7 (28.6%) | 1/34 (2.9%) | 1/18 (5.6%) | 4/59 (6.8%) | ||||
| Dysphagia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Flatulence | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Gastric polyps | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Gastritis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gastritis haemorrhagic | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Gingival pain | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Gingival recession | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Gingival swelling | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Haemorrhoids | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Ileus | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Inguinal hernia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Mouth ulceration | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Nausea | 4/7 (57.1%) | 10/34 (29.4%) | 9/18 (50%) | 23/59 (39%) | ||||
| Odynophagia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Oesophagitis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Paraesthesia oral | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Stomatitis | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Tongue discomfort | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Vomiting | 3/7 (42.9%) | 8/34 (23.5%) | 4/18 (22.2%) | 15/59 (25.4%) | ||||
| General disorders | ||||||||
| Asthenia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Catheter site pain | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Chills | 0/7 (0%) | 3/34 (8.8%) | 0/18 (0%) | 3/59 (5.1%) | ||||
| Cyst | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Fatigue | 1/7 (14.3%) | 5/34 (14.7%) | 5/18 (27.8%) | 11/59 (18.6%) | ||||
| Generalised oedema | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Impaired healing | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Influenza like illness | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Infusion site swelling | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Malaise | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Oedema peripheral | 2/7 (28.6%) | 7/34 (20.6%) | 6/18 (33.3%) | 15/59 (25.4%) | ||||
| Pain | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Peripheral swelling | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Pyrexia | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Secretion discharge | 3/7 (42.9%) | 0/34 (0%) | 0/18 (0%) | 3/59 (5.1%) | ||||
| Swelling | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic function abnormal | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Hepatitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hepatomegaly | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Immune system disorders | ||||||||
| Drug hypersensitivity | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Kidney transplant rejection | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Infections and infestations | ||||||||
| Acute sinusitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| BK virus infection | 3/7 (42.9%) | 10/34 (29.4%) | 6/18 (33.3%) | 19/59 (32.2%) | ||||
| Bronchitis | 0/7 (0%) | 4/34 (11.8%) | 0/18 (0%) | 4/59 (6.8%) | ||||
| Conjunctivitis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Cytomegalovirus infection | 0/7 (0%) | 6/34 (17.6%) | 2/18 (11.1%) | 8/59 (13.6%) | ||||
| Cytomegalovirus viraemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Diarrhoea infectious | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Epstein-Barr virus infection | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Folliculitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Fungal skin infection | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Gastroenteritis | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Gastroenteritis Escherichia coli | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gastroenteritis norovirus | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Gastroenteritis viral | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Gastrointestinal infection | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Herpes zoster | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Human polyomavirus infection | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Infection | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Influenza | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Laryngitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Latent tuberculosis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Lung infection | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Mucocutaneous candidiasis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Nasopharyngitis | 1/7 (14.3%) | 10/34 (29.4%) | 4/18 (22.2%) | 15/59 (25.4%) | ||||
| Oral candidiasis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Oral herpes | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Oral infection | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Otitis media | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pharyngitis streptococcal | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pneumocystis jirovecii pneumonia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pneumonia | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Polyomavirus-associated nephropathy | 0/7 (0%) | 3/34 (8.8%) | 1/18 (5.6%) | 4/59 (6.8%) | ||||
| Pyelonephritis | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Pyuria | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Respiratory tract infection | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Rhinitis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Sinusitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Skin infection | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Soft tissue infection | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Subcutaneous abscess | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Tinea versicolour | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Tooth infection | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Tracheobronchitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Upper respiratory tract infection | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Urinary tract infection | 1/7 (14.3%) | 8/34 (23.5%) | 7/18 (38.9%) | 16/59 (27.1%) | ||||
| Urinary tract infection viral | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Viral infection | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Wound infection bacterial | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Animal bite | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Arterial injury | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Arteriovenous fistula site complication | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Arthropod bite | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Complications of transplant surgery | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Complications of transplanted kidney | 0/7 (0%) | 3/34 (8.8%) | 2/18 (11.1%) | 5/59 (8.5%) | ||||
| Delayed graft function | 0/7 (0%) | 3/34 (8.8%) | 3/18 (16.7%) | 6/59 (10.2%) | ||||
| Fall | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Graft complication | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Incision site complication | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Incision site erythema | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Incision site haemorrhage | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Incision site pain | 3/7 (42.9%) | 6/34 (17.6%) | 2/18 (11.1%) | 11/59 (18.6%) | ||||
| Incisional hernia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Joint injury | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Ligament sprain | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Lip injury | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Post procedural complication | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Post procedural haemorrhage | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Post procedural swelling | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Postoperative wound complication | 0/7 (0%) | 5/34 (14.7%) | 1/18 (5.6%) | 6/59 (10.2%) | ||||
| Procedural pain | 0/7 (0%) | 3/34 (8.8%) | 6/18 (33.3%) | 9/59 (15.3%) | ||||
| Radius fracture | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Seroma | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Transplant dysfunction | 0/7 (0%) | 2/34 (5.9%) | 3/18 (16.7%) | 5/59 (8.5%) | ||||
| Wound complication | 0/7 (0%) | 11/34 (32.4%) | 8/18 (44.4%) | 19/59 (32.2%) | ||||
| Wound dehiscence | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Wound haematoma | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Amylase increased | 0/7 (0%) | 3/34 (8.8%) | 1/18 (5.6%) | 4/59 (6.8%) | ||||
| Aspartate aminotransferase increased | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Blood creatine phosphokinase increased | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Blood creatinine increased | 0/7 (0%) | 3/34 (8.8%) | 1/18 (5.6%) | 4/59 (6.8%) | ||||
| Blood glucose increased | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Blood lactate dehydrogenase increased | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Blood phosphorus decreased | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Blood phosphorus increased | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| C-reactive protein increased | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Cardiac murmur | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Cytomegalovirus test positive | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Drug level decreased | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Electrocardiogram ST segment abnormal | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Electrocardiogram T wave abnormal | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Gamma-glutamyltransferase increased | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Haemoglobin decreased | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Heart rate irregular | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Lipase increased | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Polyomavirus test positive | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Vitamin D decreased | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Weight decreased | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Weight increased | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| White blood cell count decreased | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| White blood cell count increased | 0/7 (0%) | 3/34 (8.8%) | 0/18 (0%) | 3/59 (5.1%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/7 (0%) | 4/34 (11.8%) | 1/18 (5.6%) | 5/59 (8.5%) | ||||
| Diabetes mellitus | 0/7 (0%) | 3/34 (8.8%) | 3/18 (16.7%) | 6/59 (10.2%) | ||||
| Dyslipidaemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Fluid overload | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Folate deficiency | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Hypercalcaemia | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Hypercholesterolaemia | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Hyperglycaemia | 3/7 (42.9%) | 4/34 (11.8%) | 4/18 (22.2%) | 11/59 (18.6%) | ||||
| Hyperkalaemia | 1/7 (14.3%) | 9/34 (26.5%) | 5/18 (27.8%) | 15/59 (25.4%) | ||||
| Hyperlipidaemia | 1/7 (14.3%) | 2/34 (5.9%) | 1/18 (5.6%) | 4/59 (6.8%) | ||||
| Hyperphosphataemia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Hypertriglyceridaemia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Hyperuricaemia | 0/7 (0%) | 4/34 (11.8%) | 1/18 (5.6%) | 5/59 (8.5%) | ||||
| Hypervolaemia | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Hypocalcaemia | 0/7 (0%) | 4/34 (11.8%) | 1/18 (5.6%) | 5/59 (8.5%) | ||||
| Hypokalaemia | 1/7 (14.3%) | 6/34 (17.6%) | 5/18 (27.8%) | 12/59 (20.3%) | ||||
| Hypomagnesaemia | 2/7 (28.6%) | 0/34 (0%) | 3/18 (16.7%) | 5/59 (8.5%) | ||||
| Hyponatraemia | 0/7 (0%) | 3/34 (8.8%) | 1/18 (5.6%) | 4/59 (6.8%) | ||||
| Hypophosphataemia | 5/7 (71.4%) | 11/34 (32.4%) | 5/18 (27.8%) | 21/59 (35.6%) | ||||
| Increased appetite | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Magnesium deficiency | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Metabolic acidosis | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Vitamin D deficiency | 2/7 (28.6%) | 2/34 (5.9%) | 1/18 (5.6%) | 5/59 (8.5%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Back pain | 0/7 (0%) | 5/34 (14.7%) | 1/18 (5.6%) | 6/59 (10.2%) | ||||
| Bursitis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Flank pain | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Groin pain | 1/7 (14.3%) | 3/34 (8.8%) | 1/18 (5.6%) | 5/59 (8.5%) | ||||
| Hypercreatinaemia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Joint effusion | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Muscle spasms | 1/7 (14.3%) | 6/34 (17.6%) | 1/18 (5.6%) | 8/59 (13.6%) | ||||
| Muscle twitching | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Muscular weakness | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Musculoskeletal discomfort | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Myalgia | 0/7 (0%) | 4/34 (11.8%) | 0/18 (0%) | 4/59 (6.8%) | ||||
| Neck pain | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Osteochondrosis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Pain in extremity | 0/7 (0%) | 2/34 (5.9%) | 2/18 (11.1%) | 4/59 (6.8%) | ||||
| Pain in jaw | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Basal cell carcinoma | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Nervous system disorders | ||||||||
| Ataxia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Burning sensation | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Dizziness | 1/7 (14.3%) | 2/34 (5.9%) | 3/18 (16.7%) | 6/59 (10.2%) | ||||
| Dizziness postural | 1/7 (14.3%) | 0/34 (0%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Headache | 1/7 (14.3%) | 6/34 (17.6%) | 4/18 (22.2%) | 11/59 (18.6%) | ||||
| Hypoaesthesia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Migraine | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Paraesthesia | 1/7 (14.3%) | 0/34 (0%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Peroneal nerve palsy | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Polyneuropathy | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Tremor | 2/7 (28.6%) | 3/34 (8.8%) | 6/18 (33.3%) | 11/59 (18.6%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Delirium | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Insomnia | 1/7 (14.3%) | 11/34 (32.4%) | 5/18 (27.8%) | 17/59 (28.8%) | ||||
| Mood swings | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Phonophobia | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Restlessness | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Renal and urinary disorders | ||||||||
| Bladder pain | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Bladder spasm | 0/7 (0%) | 3/34 (8.8%) | 0/18 (0%) | 3/59 (5.1%) | ||||
| Chronic kidney disease | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Dysuria | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Haematuria | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Leukocyturia | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Micturition urgency | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Nocturia | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Perinephric collection | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Perinephric oedema | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Polyuria | 0/7 (0%) | 5/34 (14.7%) | 0/18 (0%) | 5/59 (8.5%) | ||||
| Proteinuria | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Renal impairment | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Renal tubular acidosis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Renal tubular injury | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Renal tubular necrosis | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Sterile pyuria | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Tubulointerstitial nephritis | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Urethral pain | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Urinary incontinence | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Urinary retention | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Urinary tract disorder | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Urinary tract obstruction | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Dysmenorrhoea | 0/7 (0%) | 0/34 (0%) | 2/18 (11.1%) | 2/59 (3.4%) | ||||
| Erectile dysfunction | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Menorrhagia | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Penile oedema | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Penile pain | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Prostatomegaly | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Scrotal swelling | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Vulvovaginal pain | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/7 (0%) | 10/34 (29.4%) | 2/18 (11.1%) | 12/59 (20.3%) | ||||
| Dyspnoea | 3/7 (42.9%) | 2/34 (5.9%) | 3/18 (16.7%) | 8/59 (13.6%) | ||||
| Dyspnoea exertional | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Lung infiltration | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Nasal congestion | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Oropharyngeal pain | 0/7 (0%) | 3/34 (8.8%) | 0/18 (0%) | 3/59 (5.1%) | ||||
| Pleural effusion | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Productive cough | 1/7 (14.3%) | 1/34 (2.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Respiratory distress | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Rhinorrhoea | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Sleep apnoea syndrome | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Wheezing | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Alopecia | 1/7 (14.3%) | 2/34 (5.9%) | 2/18 (11.1%) | 5/59 (8.5%) | ||||
| Decubitus ulcer | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Dermatitis | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Hyperhidrosis | 0/7 (0%) | 3/34 (8.8%) | 0/18 (0%) | 3/59 (5.1%) | ||||
| Lipohypertrophy | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Night sweats | 0/7 (0%) | 2/34 (5.9%) | 1/18 (5.6%) | 3/59 (5.1%) | ||||
| Pityriasis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Pruritus | 0/7 (0%) | 1/34 (2.9%) | 2/18 (11.1%) | 3/59 (5.1%) | ||||
| Rash | 0/7 (0%) | 0/34 (0%) | 3/18 (16.7%) | 3/59 (5.1%) | ||||
| Skin lesion | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Urticaria | 0/7 (0%) | 1/34 (2.9%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/7 (0%) | 0/34 (0%) | 1/18 (5.6%) | 1/59 (1.7%) | ||||
| Haematoma | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Hot flush | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
| Hypertension | 1/7 (14.3%) | 13/34 (38.2%) | 6/18 (33.3%) | 20/59 (33.9%) | ||||
| Hypotension | 0/7 (0%) | 2/34 (5.9%) | 3/18 (16.7%) | 5/59 (8.5%) | ||||
| Lymphocele | 0/7 (0%) | 1/34 (2.9%) | 1/18 (5.6%) | 2/59 (3.4%) | ||||
| Orthostatic hypotension | 1/7 (14.3%) | 0/34 (0%) | 0/18 (0%) | 1/59 (1.7%) | ||||
| Poor venous access | 0/7 (0%) | 2/34 (5.9%) | 0/18 (0%) | 2/59 (3.4%) | ||||
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:
NCT02217410
Other Study ID Numbers:
- CCFZ533X2201
First Posted:
Aug 15, 2014
Last Update Posted:
Sep 28, 2021
Last Verified:
Sep 1, 2021