Study of CP-751,871 in Combination With Docetaxel and Prednisone in Patients With Hormone Insensitive Prostate Cancer (HRPC)
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00313781
Collaborator
(none)
204
18
2
67
11.3
0.2
Study Details
Study Description
Brief Summary
To test the efficacy of CP-751,871 combined with docetaxel and prednisone in the treatment of prostate cancer that is refractory to hormone therapy
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
204 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Non-Comparative, Two-Arm Open Label, Multiple-Center Study Of CP-751,871 In Combination With Docetaxel/Prednisone In Chemotherapy- Naive (Arm A) And Docetaxel/Prednisone Refractory (Arm B) Patients With Hormone Insensitive Prostate Cancer
Study Start Date
:
May 1, 2006
Actual Primary Completion Date
:
Apr 1, 2011
Actual Study Completion Date
:
Dec 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A For patients treated with docetaxel and prednisone only, who progress during treatment, CP-751,871 will be added to the regimen to test reversibility of chemoresistance. |
Drug: CP-751,871
CP-750,871 is administered intravenously at a dose of 20 mg/kg on day 1 of each 21-day cycle (for patient convenience and logistical management, the dose of CP-751,871 may be deferred up to 7 days).
Drug: docetaxel
Docetaxel is administered IV on day 1 of each 21-day cycle, at a dose of 75 mg/m2.
Drug: prednisone
Prednisone is administered at a dose of 5 mg twice daily.
|
| Active Comparator: B
|
Drug: docetaxel
Docetaxel is administered IV on day 1 of each 21-day cycle, at a dose of 75 mg/m2.
Drug: prednisone
Prednisone is administered at a dose of 5 mg twice daily.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Prostate Specific Antigen (PSA) Best Response [Baseline, Day 1 and Day 15 of each cycle, end of treatment (up to 28 days post last dose) and follow-up (monthly, up to 150 days post last dose)]
Percentage of participants with PSA best response of either PSA normalization (PN) or partial PSA response (PR) relative to the total number of participants evaluable for response. PN was defined as PSA =< 0.2 nanogram/milliliter (ng/ml) on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression. PP was defined as >= 50% decrease in PSA from baseline on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression.
Secondary Outcome Measures
- Progression Free Survival (PFS) [Baseline, Day 15 of each cycle and follow-up (monthly, up to 150 days post last dose)]
PFS was defined as the time from randomization to first event of disease progression. Disease progression events were defined as the following: PSA progression,objective disease progression as per RECIST, death, and discontinuation of treatment due to symptomatic deterioration. PSA progression was defined as the time-point of PSA progression on 2 successive evaluations taken 1 week apart after dosing in cycle 3.
- Human Anti-human Antibody (HAHA) at Baseline (Day 1 of Cycle 1) [Baseline (Day 1 of Cycle 1)]
Levels of HAHA in serum were detected at baseline.
- Human Anti-human Antibody (HAHA) at the Last Follow-up Visit [The last follow-up visit (150 days post last dose)]
Levels of HAHA in serum were detected at the last follow-up visit.
- Population PK Parameters of CP-751,871 [Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)]
Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for CP-751,871 and to determine inter-individual and residual variability in population clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured CP-751,871 concentrations
- Total Number of Circulation Tumor Cells (CTCs) [Baseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose)]
Blood samples were collected and processed to enumerate the number of total CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive epithelial cell adhesion molecule (EpCAM) and cytokeratin staining.
- Total Number of the Insulin Like Growth Factor Receptor Type 1 (IGF-1R) Positive CTCs [Baseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose)]
Blood samples were collected to enumerate the number of total IGF-1R positive CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive EpCAM and cytokeratin staining. A separate CellSave tube of cells was also collected and processed with cell surface staining of IGF-1R to enumerate surfaces of IGF-1R-positive CTCs.
- Quality of Life Measured by the Functional Assessment of Cancer Treatment-Prostate (FACT-P) [Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose)]
The FACT-P was a 39-item participant questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items were scored from 0 (not at all) to 4 (very much). The total FACT-P score ranged from 0-156, with higher scores representing a better QoL with fewer symptoms. A score of 156 represented the best outcome.
- Pain Measured by the Modified Brief Pain Inventory-Short Form (mBPI-sf Modified Pfizer) [Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose)]
The mBPI-sf was a self administered questionnaire developed to assess pain severity and pain interference with functional activities during a 24-hour period prior to evaluation. For the worst pain item of the mBPI-sf scale (11 point Likert scale; range: 0 [no pain] to 10 [pain as bad as you can imagine]), participants were asked to rate their pain by marking an "X" in one of the 10 boxes that best described their pain at its worst in the last 24 hours post surgery and at least 12 hours after discontinuation of the peripheral nerve block or neuraxial block.
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for CP-751,871 [Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)]
Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration.
- Maximum Observed Plasma Concentration (Cmax) for CP-751,871 [Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)]
- Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871 [Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)]
- Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-tau) for CP-751,871 [Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of metastatic, progressive hormone refractory prostate cancer
-
Adequate bone marrow, liver and kidney function
Exclusion Criteria:
- Previous treatment with chemotherapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Los Angeles | California | United States | 90048 |
| 2 | Pfizer Investigational Site | New York | New York | United States | 10032 |
| 3 | Pfizer Investigational Site | Cleveland | Ohio | United States | 44106 |
| 4 | Pfizer Investigational Site | Cleveland | Ohio | United States | 44195-0001 |
| 5 | Pfizer Investigational Site | Orange Village | Ohio | United States | 44122 |
| 6 | Pfizer Investigational Site | Philadelphia | Pennsylvania | United States | 19111-2497 |
| 7 | Pfizer Investigational Site | Montreal | Quebec | Canada | H2L 4M1 |
| 8 | Pfizer Investigational Site | Montreal | Quebec | Canada | H3T 1E2 |
| 9 | Pfizer Investigational Site | Berlin | Germany | 12200 | |
| 10 | Pfizer Investigational Site | Muenchen | Germany | 81675 | |
| 11 | Pfizer Investigational Site | Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 12 | Pfizer Investigational Site | A Coruña | Spain | 15006 | |
| 13 | Pfizer Investigational Site | Barcelona | Spain | 08035 | |
| 14 | Pfizer Investigational Site | St. Gallen | Switzerland | CH-9007 | |
| 15 | Pfizer Investigational Site | Sutton | Surrey | United Kingdom | SM2 5PT |
| 16 | Pfizer Investigational Site | Glasgow | United Kingdom | G12 0YH | |
| 17 | Pfizer Investigational Site | Glasgow | United Kingdom | G52 3NQ | |
| 18 | Pfizer Investigational Site | Guildford | United Kingdom | GU2 7WG |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00313781
Other Study ID Numbers:
- A4021011
First Posted:
Apr 12, 2006
Last Update Posted:
Apr 11, 2013
Last Verified:
Mar 1, 2013
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion intravenously (IV) over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21 days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Period Title: Before Crossover | |||
| STARTED | 102 | 102 | 0 |
| Treated | 97 | 102 | 0 |
| COMPLETED | 27 | 23 | 0 |
| NOT COMPLETED | 75 | 79 | 0 |
| Period Title: Before Crossover | |||
| STARTED | 0 | 0 | 37 |
| COMPLETED | 0 | 0 | 10 |
| NOT COMPLETED | 0 | 0 | 27 |
Baseline Characteristics
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Total |
|---|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Total of all reporting groups |
| Overall Participants | 102 | 102 | 204 |
| Age, Customized (Number) [Number] | |||
| Less than (<) 18 years |
0
0%
|
0
0%
|
0
0%
|
| 18 to 44 years |
0
0%
|
1
1%
|
1
0.5%
|
| 45 to 64 years |
26
25.5%
|
32
31.4%
|
58
28.4%
|
| Greater than or equal to (>=) 65 years |
76
74.5%
|
69
67.6%
|
145
71.1%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
102
100%
|
102
100%
|
204
100%
|
Outcome Measures
| Title | Percentage of Participants With Prostate Specific Antigen (PSA) Best Response |
|---|---|
| Description | Percentage of participants with PSA best response of either PSA normalization (PN) or partial PSA response (PR) relative to the total number of participants evaluable for response. PN was defined as PSA =< 0.2 nanogram/milliliter (ng/ml) on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression. PP was defined as >= 50% decrease in PSA from baseline on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression. |
| Time Frame | Baseline, Day 1 and Day 15 of each cycle, end of treatment (up to 28 days post last dose) and follow-up (monthly, up to 150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable population: All enrolled participants who had a baseline PSA reference value and received at least one dose of assigned treatment with the exception of those participants without symptomatic or objective progression (participants with PSA progression only) who withdraw consent prior to Cycle 3. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 87 | 98 | 32 |
| Mean (90% Confidence Interval) [Percentage of participants] |
51.7
50.7%
|
60.2
59%
|
28.1
13.8%
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from randomization to first event of disease progression. Disease progression events were defined as the following: PSA progression,objective disease progression as per RECIST, death, and discontinuation of treatment due to symptomatic deterioration. PSA progression was defined as the time-point of PSA progression on 2 successive evaluations taken 1 week apart after dosing in cycle 3. |
| Time Frame | Baseline, Day 15 of each cycle and follow-up (monthly, up to 150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all participants who were enrolled into the study and received at least one assigned treatment. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 97 | 102 | 37 |
| Median (95% Confidence Interval) [Months] |
4.9
|
7.7
|
4.0
|
| Title | Human Anti-human Antibody (HAHA) at Baseline (Day 1 of Cycle 1) |
|---|---|
| Description | Levels of HAHA in serum were detected at baseline. |
| Time Frame | Baseline (Day 1 of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were enrolled in the study, received at least one assigned treatment and had available HAHA assessment. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone |
|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. |
| Measure Participants | 49 | 41 |
| Mean (Standard Deviation) [mg/deciliter (dl)] |
1130.3
(406.49)
|
1338.1
(804.30)
|
| Title | Human Anti-human Antibody (HAHA) at the Last Follow-up Visit |
|---|---|
| Description | Levels of HAHA in serum were detected at the last follow-up visit. |
| Time Frame | The last follow-up visit (150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were enrolled in the study, received at least one assigned treatment and had HAHA available assessment. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 32 | 13 | 14 |
| Mean (Standard Deviation) [mg/dl] |
944.81
(946.42)
|
819.00
(487.94)
|
970.86
(295.28)
|
| Title | Population PK Parameters of CP-751,871 |
|---|---|
| Description | Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for CP-751,871 and to determine inter-individual and residual variability in population clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured CP-751,871 concentrations |
| Time Frame | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Total Number of Circulation Tumor Cells (CTCs) |
|---|---|
| Description | Blood samples were collected and processed to enumerate the number of total CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive epithelial cell adhesion molecule (EpCAM) and cytokeratin staining. |
| Time Frame | Baseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who were enrolled to the study were included in the analysis. n = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone |
|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. |
| Measure Participants | 46 | 39 |
| Baseline (Cycle 1 Day 1) (n=46, 39) |
105.17
(259.60)
|
213.23
(555.82)
|
| Cycle 3 Day1 (n=28, 29) |
6.39
(11.39)
|
12.21
(27.52)
|
| Cycle 5 Day 1 (n=25, 23) |
15.20
(46.40)
|
17.78
(28.11)
|
| Title | Total Number of the Insulin Like Growth Factor Receptor Type 1 (IGF-1R) Positive CTCs |
|---|---|
| Description | Blood samples were collected to enumerate the number of total IGF-1R positive CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive EpCAM and cytokeratin staining. A separate CellSave tube of cells was also collected and processed with cell surface staining of IGF-1R to enumerate surfaces of IGF-1R-positive CTCs. |
| Time Frame | Baseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who were enrolled to the study were included in the analysis. n = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone |
|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. |
| Measure Participants | 22 | 18 |
| Baseline (Cycle 1 Day 1) (n=22, 18) |
24.73
(25.32)
|
54.94
(55.52)
|
| Cycle 3 Day1 (n=12, 15) |
2.33
(4.48)
|
4.93
(7.74)
|
| Cycle 5 Day 1 (n=11, 10) |
2.00
(4.49)
|
3.90
(6.03)
|
| Title | Quality of Life Measured by the Functional Assessment of Cancer Treatment-Prostate (FACT-P) |
|---|---|
| Description | The FACT-P was a 39-item participant questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items were scored from 0 (not at all) to 4 (very much). The total FACT-P score ranged from 0-156, with higher scores representing a better QoL with fewer symptoms. A score of 156 represented the best outcome. |
| Time Frame | Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The summary table was not provided based on 1) the negative primary finding of the study that CP-751,871 did not improve response in CP-751,871+Docetaxel + Prednisone and had significantly worse PFS than Docetaxel +Prednisone, which rendered the patient reported outcome (PRO) summary irrelevant 2) lack of resources as the program was terminated. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 0 | 0 | 0 |
| Title | Pain Measured by the Modified Brief Pain Inventory-Short Form (mBPI-sf Modified Pfizer) |
|---|---|
| Description | The mBPI-sf was a self administered questionnaire developed to assess pain severity and pain interference with functional activities during a 24-hour period prior to evaluation. For the worst pain item of the mBPI-sf scale (11 point Likert scale; range: 0 [no pain] to 10 [pain as bad as you can imagine]), participants were asked to rate their pain by marking an "X" in one of the 10 boxes that best described their pain at its worst in the last 24 hours post surgery and at least 12 hours after discontinuation of the peripheral nerve block or neuraxial block. |
| Time Frame | Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The summary table was not provided based on 1) the negative primary finding of the study that CP-751,871 did not improve response in CP-751,871+Docetaxel + Prednisone and had significantly worse PFS than Docetaxel +Prednisone, which rendered the PRO summary irrelevant 2) lack of resources as the program was terminated. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 0 | 0 | 0 |
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for CP-751,871 |
|---|---|
| Description | Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration. |
| Time Frame | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The summary table of this outcome measure was not provided based on lack of resources as the program was terminated. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 0 | 0 |
| Title | Maximum Observed Plasma Concentration (Cmax) for CP-751,871 |
|---|---|
| Description | |
| Time Frame | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The summary table of this outcome measure was not provided based on lack of resources as the program was terminated. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 0 | 0 |
| Title | Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871 |
|---|---|
| Description | |
| Time Frame | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The summary table of this outcome measure was not provided based on lack of resources as the program was terminated. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 0 | 0 |
| Title | Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-tau) for CP-751,871 |
|---|---|
| Description | |
| Time Frame | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The summary table of this outcome measure was not provided based on lack of resources as the program was terminated. |
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover |
|---|---|---|
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. 199 out of 204 participants were treated. | |||||
| Arm/Group Title | CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover | |||
| Arm/Group Description | Participants received docetaxel 75 milligram(mg)/square meter(m^2) infusion IV over 1 hour on Day 1, followed by CP-751,871 20 mg/kilogram (kg) infusion IV on Day 1 along with prednisone 5 mg twice daily (BID) in a 21-days cycle, up to 17 cycles. | Participants received docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 along with prednisone 5 mg BID in a 21 days cycle, up to 17 cycles. | Participants from the "Docetaxel+Prednisone" group who, after disease progression while receiving docetaxel and prednisone alone, opted to receive CP-751,871 20 mg/kg infusion IV on Day 1 of a 21 days cycle, along with docetaxel 75 mg/m^2 infusion IV over 1 hour on Day 1 and prednisone 5 mg BID, up to 17 cycles. | |||
All Cause Mortality |
||||||
| CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 64/97 (66%) | 37/102 (36.3%) | 20/37 (54.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/97 (2.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Febrile neutropenia | 12/97 (12.4%) | 7/102 (6.9%) | 2/37 (5.4%) | |||
| Leukopenia | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Neutropenia | 10/97 (10.3%) | 2/102 (2%) | 0/37 (0%) | |||
| Thrombocytopenia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Cardiac disorders | ||||||
| Acute coronary syndrome | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Acute myocardial infarction | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Atrial fibrillation | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Cardiac failure | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Cardiogenic shock | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Cardiopulmonary failure | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Myocardial infarction | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Myocardial ischaemia | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Endocrine disorders | ||||||
| Hypercalcaemia of malignancy | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Eye disorders | ||||||
| Vitreous haemorrhage | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Anal fissure | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Colitis ischaemic | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Diarrhoea | 9/97 (9.3%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Dysphagia | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Faecaloma | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Intestinal perforation | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Nausea | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Rectal haemorrhage | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Stomatitis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Upper gastrointestinal haemorrhage | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Vomiting | 4/97 (4.1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| General disorders | ||||||
| Asthenia | 4/97 (4.1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Chest pain | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Death | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Disease progression | 8/97 (8.2%) | 3/102 (2.9%) | 6/37 (16.2%) | |||
| Drug interaction | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Fatigue | 5/97 (5.2%) | 0/102 (0%) | 3/37 (8.1%) | |||
| Pyrexia | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Infections and infestations | ||||||
| Abscess | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Candidiasis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Cellulitis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Clostridial infection | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Diverticulitis | 4/97 (4.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Endocarditis bacterial | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Gastroenteritis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Gastrointestinal fungal infection | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Infection | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Localised infection | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Lower respiratory tract infection | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Neutropenic sepsis | 3/97 (3.1%) | 3/102 (2.9%) | 0/37 (0%) | |||
| Peridiverticular abscess | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Pneumonia | 2/97 (2.1%) | 4/102 (3.9%) | 2/37 (5.4%) | |||
| Salmonellosis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Septic shock | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Soft tissue infection | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Subcutaneous abscess | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Urinary tract infection | 4/97 (4.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Femoral neck fracture | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Foot fracture | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Joint dislocation | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Rib fracture | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Investigations | ||||||
| Blood creatinine increased | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Troponin T increased | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Weight decreased | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Dehydration | 4/97 (4.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Diabetic ketoacidosis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Hyperglycaemia | 11/97 (11.3%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Hyperkalaemia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypoglycaemia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Hyponatraemia | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Arthropathy | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Back pain | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Bone pain | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Flank pain | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Muscular weakness | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Myopathy | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Osteonecrosis | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Pain in extremity | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Pathological fracture | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Spinal column stenosis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Nervous system disorders | ||||||
| Cerebral infarction | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Cerebrovascular accident | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Cognitive disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Convulsion | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Dizziness | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lethargy | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Mental impairment | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Peripheral motor neuropathy | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Presyncope | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Speech disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Spinal cord compression | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Syncope | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Psychiatric disorders | ||||||
| Confusional state | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Major depression | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Mental status changes | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Suicide attempt | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Renal and urinary disorders | ||||||
| Bladder tamponade | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Haematuria | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Renal failure | 4/97 (4.1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Renal failure acute | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Renal impairment | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Urethral obstruction | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Urinary retention | 0/97 (0%) | 1/102 (1%) | 2/37 (5.4%) | |||
| Urinary tract obstruction | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Epistaxis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Hypoxia | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Pharyngeal inflammation | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Pneumonia aspiration | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Pulmonary embolism | 6/97 (6.2%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Respiratory failure | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Haematoma | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypotension | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Hypovolaemic shock | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Vasculitis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| CP-751,871+Docetaxel+Prednisone | Docetaxel+Prednisone | Docetaxel+Prednisone+CP-751,871 Crossover | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 96/97 (99%) | 53/102 (52%) | 21/37 (56.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 13/97 (13.4%) | 21/102 (20.6%) | 11/37 (29.7%) | |||
| Febrile neutropenia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypochromic anaemia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Leukopenia | 22/97 (22.7%) | 24/102 (23.5%) | 4/37 (10.8%) | |||
| Lymphadenitis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lymphadenopathy | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lymphopenia | 8/97 (8.2%) | 10/102 (9.8%) | 4/37 (10.8%) | |||
| Neutropenia | 34/97 (35.1%) | 37/102 (36.3%) | 10/37 (27%) | |||
| Normochromic normocytic anaemia | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Thrombocytopenia | 5/97 (5.2%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Cardiac disorders | ||||||
| Atrioventricular block first degree | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Bradycardia | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Cardiac failure | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Coronary artery disease | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Diastolic dysfunction | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Extrasystoles | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Mitral valve prolapse | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Palpitations | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Sinus bradycardia | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Tachycardia | 2/97 (2.1%) | 2/102 (2%) | 0/37 (0%) | |||
| Ventricular extrasystoles | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Cerumen impaction | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Deafness | 7/97 (7.2%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Deafness bilateral | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Deafness unilateral | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Ear discomfort | 6/97 (6.2%) | 0/102 (0%) | 0/37 (0%) | |||
| Ear disorder | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Ear haemorrhage | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Ear pain | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Hearing impaired | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypoacusis | 7/97 (7.2%) | 0/102 (0%) | 0/37 (0%) | |||
| Tinnitus | 4/97 (4.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Vertigo | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Cushingoid | 2/97 (2.1%) | 3/102 (2.9%) | 0/37 (0%) | |||
| Hypothyroidism | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Eye disorders | ||||||
| Blepharitis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Cataract | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Conjunctival pallor | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Conjunctivitis | 6/97 (6.2%) | 5/102 (4.9%) | 2/37 (5.4%) | |||
| Dry eye | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Ectropion | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Eye haemorrhage | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Eye pain | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Eye pruritus | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Keratoconjunctivitis sicca | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Lacrimation increased | 9/97 (9.3%) | 8/102 (7.8%) | 6/37 (16.2%) | |||
| Ocular hyperaemia | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Periorbital oedema | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Photophobia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Retinal detachment | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Retinal disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Scleral haemorrhage | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Vision blurred | 5/97 (5.2%) | 5/102 (4.9%) | 2/37 (5.4%) | |||
| Visual impairment | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Vitreous haemorrhage | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 1/97 (1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Abdominal pain | 8/97 (8.2%) | 2/102 (2%) | 3/37 (8.1%) | |||
| Abdominal pain lower | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Abdominal pain upper | 6/97 (6.2%) | 2/102 (2%) | 0/37 (0%) | |||
| Abdominal tenderness | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Anal fissure | 5/97 (5.2%) | 0/102 (0%) | 0/37 (0%) | |||
| Anal fistula | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Anal haemorrhage | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Anal inflammation | 3/97 (3.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Anorectal discomfort | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Anorectal disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Colitis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Constipation | 22/97 (22.7%) | 17/102 (16.7%) | 8/37 (21.6%) | |||
| Defaecation urgency | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Dental caries | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Diarrhoea | 64/97 (66%) | 38/102 (37.3%) | 14/37 (37.8%) | |||
| Dry mouth | 6/97 (6.2%) | 4/102 (3.9%) | 3/37 (8.1%) | |||
| Dyspepsia | 8/97 (8.2%) | 6/102 (5.9%) | 3/37 (8.1%) | |||
| Dysphagia | 2/97 (2.1%) | 3/102 (2.9%) | 2/37 (5.4%) | |||
| Faecal incontinence | 2/97 (2.1%) | 2/102 (2%) | 2/37 (5.4%) | |||
| Faeces discoloured | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Flatulence | 1/97 (1%) | 2/102 (2%) | 2/37 (5.4%) | |||
| Frequent bowel movements | 1/97 (1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Gastritis | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Gastrointestinal oedema | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Gastrointestinal toxicity | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Gastrooesophageal reflux disease | 0/97 (0%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Gingival bleeding | 3/97 (3.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Gingival pain | 5/97 (5.2%) | 1/102 (1%) | 0/37 (0%) | |||
| Gingival ulceration | 1/97 (1%) | 1/102 (1%) | 2/37 (5.4%) | |||
| Gingivitis | 2/97 (2.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Glossodynia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Haematochezia | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Haemorrhoidal haemorrhage | 2/97 (2.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Haemorrhoids | 5/97 (5.2%) | 3/102 (2.9%) | 2/37 (5.4%) | |||
| Hiatus hernia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Hypoaesthesia oral | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Large intestinal haemorrhage | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Lip swelling | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Lower gastrointestinal haemorrhage | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Melaena | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Mouth ulceration | 2/97 (2.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Nausea | 34/97 (35.1%) | 28/102 (27.5%) | 10/37 (27%) | |||
| Odynophagia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Oesophagitis | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Oral pain | 0/97 (0%) | 4/102 (3.9%) | 1/37 (2.7%) | |||
| Pancreatitis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Periodontal disease | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Proctalgia | 5/97 (5.2%) | 2/102 (2%) | 3/37 (8.1%) | |||
| Proctitis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Rectal discharge | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Rectal fissure | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Rectal haemorrhage | 10/97 (10.3%) | 6/102 (5.9%) | 2/37 (5.4%) | |||
| Rectal tenesmus | 4/97 (4.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Salivary hypersecretion | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Sensitivity of teeth | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Steatorrhoea | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Stomatitis | 18/97 (18.6%) | 8/102 (7.8%) | 3/37 (8.1%) | |||
| Tongue disorder | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Tongue oedema | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Tongue ulceration | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Tooth loss | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Toothache | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Vomiting | 19/97 (19.6%) | 12/102 (11.8%) | 10/37 (27%) | |||
| Vomiting projectile | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| General disorders | ||||||
| Asthenia | 38/97 (39.2%) | 33/102 (32.4%) | 13/37 (35.1%) | |||
| Catheter site pruritus | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Chest discomfort | 1/97 (1%) | 4/102 (3.9%) | 1/37 (2.7%) | |||
| Chest pain | 2/97 (2.1%) | 3/102 (2.9%) | 2/37 (5.4%) | |||
| Chills | 6/97 (6.2%) | 6/102 (5.9%) | 3/37 (8.1%) | |||
| Death | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Device occlusion | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Discomfort | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Disease progression | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Energy increased | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Extravasation | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Face oedema | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Fatigue | 40/97 (41.2%) | 36/102 (35.3%) | 14/37 (37.8%) | |||
| Feeling cold | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Feeling hot | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Gait disturbance | 2/97 (2.1%) | 2/102 (2%) | 2/37 (5.4%) | |||
| General physical health deterioration | 2/97 (2.1%) | 0/102 (0%) | 2/37 (5.4%) | |||
| Influenza like illness | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Infusion site pruritus | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Injection site reaction | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Irritability | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Local swelling | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Malaise | 0/97 (0%) | 3/102 (2.9%) | 0/37 (0%) | |||
| Mucosal dryness | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Mucosal inflammation | 15/97 (15.5%) | 12/102 (11.8%) | 1/37 (2.7%) | |||
| Oedema | 1/97 (1%) | 2/102 (2%) | 2/37 (5.4%) | |||
| Oedema peripheral | 10/97 (10.3%) | 28/102 (27.5%) | 4/37 (10.8%) | |||
| Pain | 6/97 (6.2%) | 3/102 (2.9%) | 4/37 (10.8%) | |||
| Premature ageing | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Pyrexia | 12/97 (12.4%) | 13/102 (12.7%) | 4/37 (10.8%) | |||
| Sensation of pressure | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Temperature intolerance | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Therapeutic response unexpected | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Thirst | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Ulcer | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatomegaly | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Jaundice | 2/97 (2.1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Immune system disorders | ||||||
| Allergic oedema | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Drug hypersensitivity | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Hypersensitivity | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Infections and infestations | ||||||
| Anorectal infection | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Bronchitis | 1/97 (1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Candidiasis | 2/97 (2.1%) | 3/102 (2.9%) | 0/37 (0%) | |||
| Catheter site cellulitis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Cellulitis | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Conjunctivitis infective | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Device related infection | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Diverticulitis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Ear infection | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Gastric infection | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Gastroenteritis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Gastroenteritis viral | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Gastrointestinal infection | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Genital candidiasis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Gingival infection | 3/97 (3.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Herpes virus infection | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Herpes zoster | 1/97 (1%) | 3/102 (2.9%) | 1/37 (2.7%) | |||
| Infection | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Influenza | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Localised infection | 3/97 (3.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Lower respiratory tract infection | 4/97 (4.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lung infection | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Nail infection | 0/97 (0%) | 4/102 (3.9%) | 0/37 (0%) | |||
| Nasopharyngitis | 7/97 (7.2%) | 11/102 (10.8%) | 4/37 (10.8%) | |||
| Onychomycosis | 2/97 (2.1%) | 5/102 (4.9%) | 2/37 (5.4%) | |||
| Oral candidiasis | 4/97 (4.1%) | 4/102 (3.9%) | 0/37 (0%) | |||
| Oral herpes | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Oral viral infection | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Oropharyngeal candidiasis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Paronychia | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Parotitis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Pharyngitis | 0/97 (0%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Pneumonia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Respiratory tract infection | 4/97 (4.1%) | 3/102 (2.9%) | 2/37 (5.4%) | |||
| Rhinitis | 3/97 (3.1%) | 6/102 (5.9%) | 2/37 (5.4%) | |||
| Sepsis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Septic shock | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Sinusitis | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Skin infection | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Soft tissue infection | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Tinea pedis | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Tooth infection | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Upper respiratory tract infection | 4/97 (4.1%) | 6/102 (5.9%) | 0/37 (0%) | |||
| Urinary tract infection | 12/97 (12.4%) | 7/102 (6.9%) | 2/37 (5.4%) | |||
| Viral infection | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Wound infection | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Arthropod sting | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Chemical injury | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Contusion | 7/97 (7.2%) | 4/102 (3.9%) | 2/37 (5.4%) | |||
| Epicondylitis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Excoriation | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Fall | 9/97 (9.3%) | 0/102 (0%) | 3/37 (8.1%) | |||
| Foot fracture | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Head injury | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Injury | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Joint sprain | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Laceration | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Limb injury | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Nail injury | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Neck injury | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Rib fracture | 2/97 (2.1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Skeletal injury | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Splinter | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Subcutaneous haematoma | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Superficial injury of eye | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Tooth fracture | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Traumatic brain injury | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Upper limb fracture | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Wound | 2/97 (2.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Investigations | ||||||
| Activated partial thromboplastin time prolonged | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Alanine aminotransferase | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Alanine aminotransferase increased | 7/97 (7.2%) | 1/102 (1%) | 0/37 (0%) | |||
| Aspartate aminotransferase | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Aspartate aminotransferase increased | 2/97 (2.1%) | 2/102 (2%) | 0/37 (0%) | |||
| Blood albumin decreased | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Blood alkaline phosphatase | 1/97 (1%) | 2/102 (2%) | 0/37 (0%) | |||
| Blood alkaline phosphatase increased | 1/97 (1%) | 4/102 (3.9%) | 3/37 (8.1%) | |||
| Blood amylase increased | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Blood bicarbonate decreased | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Blood bilirubin increased | 1/97 (1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Blood creatinine increased | 9/97 (9.3%) | 0/102 (0%) | 2/37 (5.4%) | |||
| Blood glucose | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Blood glucose abnormal | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Blood glucose increased | 4/97 (4.1%) | 3/102 (2.9%) | 3/37 (8.1%) | |||
| Blood lactate dehydrogenase increased | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Blood magnesium decreased | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Blood magnesium increased | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Blood phosphorus | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Blood potassium decreased | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Blood potassium increased | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Blood sodium decreased | 1/97 (1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Blood urea increased | 4/97 (4.1%) | 1/102 (1%) | 2/37 (5.4%) | |||
| Blood uric acid increased | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Gamma-glutamyltransferase increased | 4/97 (4.1%) | 3/102 (2.9%) | 1/37 (2.7%) | |||
| General physical condition abnormal | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Granulocyte count decreased | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Haemoglobin | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Haemoglobin decreased | 1/97 (1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| International normalised ratio abnormal | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| International normalised ratio increased | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Lipase increased | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lymphocyte count | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Lymphocyte count decreased | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Murphy's sign positive | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Neutrophil count decreased | 4/97 (4.1%) | 2/102 (2%) | 0/37 (0%) | |||
| Neutrophil count increased | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Platelet count | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Platelet count decreased | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Platelet count increased | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Renal function test abnormal | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Troponin increased | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Weight decreased | 18/97 (18.6%) | 8/102 (7.8%) | 6/37 (16.2%) | |||
| Weight increased | 1/97 (1%) | 3/102 (2.9%) | 1/37 (2.7%) | |||
| White blood cell count | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| White blood cell count decreased | 4/97 (4.1%) | 3/102 (2.9%) | 0/37 (0%) | |||
| White blood cell count increased | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Cachexia | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Central obesity | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Decreased appetite | 56/97 (57.7%) | 32/102 (31.4%) | 20/37 (54.1%) | |||
| Dehydration | 3/97 (3.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Fluid retention | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Hyperalbuminaemia | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Hypercholesterolaemia | 2/97 (2.1%) | 1/102 (1%) | 2/37 (5.4%) | |||
| Hyperglycaemia | 34/97 (35.1%) | 15/102 (14.7%) | 14/37 (37.8%) | |||
| Hyperkalaemia | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Hypermagnesaemia | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Hypernatraemia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hyperuricaemia | 3/97 (3.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Hypoalbuminaemia | 4/97 (4.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypocalcaemia | 3/97 (3.1%) | 3/102 (2.9%) | 1/37 (2.7%) | |||
| Hypoglycaemia | 4/97 (4.1%) | 4/102 (3.9%) | 1/37 (2.7%) | |||
| Hypokalaemia | 7/97 (7.2%) | 4/102 (3.9%) | 2/37 (5.4%) | |||
| Hypomagnesaemia | 4/97 (4.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Hyponatraemia | 5/97 (5.2%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Hypophagia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypophosphataemia | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Hypoproteinaemia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Increased appetite | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Malnutrition | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Polydipsia | 4/97 (4.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Vitamin B12 deficiency | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Joint stiffness | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 10/97 (10.3%) | 15/102 (14.7%) | 10/37 (27%) | |||
| Arthritis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Arthropathy | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Back pain | 20/97 (20.6%) | 13/102 (12.7%) | 11/37 (29.7%) | |||
| Bone pain | 3/97 (3.1%) | 7/102 (6.9%) | 1/37 (2.7%) | |||
| Coccydynia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Exostosis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Flank pain | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Groin pain | 3/97 (3.1%) | 2/102 (2%) | 2/37 (5.4%) | |||
| Joint swelling | 3/97 (3.1%) | 2/102 (2%) | 2/37 (5.4%) | |||
| Limb discomfort | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Mobility decreased | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Muscle atrophy | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Muscle spasms | 19/97 (19.6%) | 7/102 (6.9%) | 6/37 (16.2%) | |||
| Muscular weakness | 13/97 (13.4%) | 11/102 (10.8%) | 6/37 (16.2%) | |||
| Musculoskeletal chest pain | 2/97 (2.1%) | 3/102 (2.9%) | 3/37 (8.1%) | |||
| Musculoskeletal discomfort | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Musculoskeletal pain | 14/97 (14.4%) | 8/102 (7.8%) | 5/37 (13.5%) | |||
| Musculoskeletal stiffness | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Myalgia | 6/97 (6.2%) | 13/102 (12.7%) | 4/37 (10.8%) | |||
| Myopathy | 4/97 (4.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Neck mass | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Neck pain | 4/97 (4.1%) | 5/102 (4.9%) | 1/37 (2.7%) | |||
| Osteopenia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Osteoporosis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Pain in extremity | 14/97 (14.4%) | 18/102 (17.6%) | 10/37 (27%) | |||
| Pain in jaw | 3/97 (3.1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Trigger finger | 3/97 (3.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Upper extremity mass | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Benign neoplasm of testis | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Bone neoplasm | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Nervous system disorders | ||||||
| Ageusia | 2/97 (2.1%) | 3/102 (2.9%) | 1/37 (2.7%) | |||
| Amnesia | 5/97 (5.2%) | 1/102 (1%) | 2/37 (5.4%) | |||
| Aphonia | 2/97 (2.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Ataxia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Balance disorder | 4/97 (4.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Burning sensation | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Cerebral small vessel ischaemic disease | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Cognitive disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Dementia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Depressed level of consciousness | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Disturbance in attention | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Dizziness | 10/97 (10.3%) | 16/102 (15.7%) | 6/37 (16.2%) | |||
| Dizziness exertional | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Dizziness postural | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Drooling | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Dysarthria | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Dysgeusia | 37/97 (38.1%) | 37/102 (36.3%) | 12/37 (32.4%) | |||
| Extrapyramidal disorder | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Headache | 9/97 (9.3%) | 7/102 (6.9%) | 1/37 (2.7%) | |||
| Hypoaesthesia | 3/97 (3.1%) | 8/102 (7.8%) | 2/37 (5.4%) | |||
| Hypogeusia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lethargy | 15/97 (15.5%) | 16/102 (15.7%) | 5/37 (13.5%) | |||
| Loss of consciousness | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Memory impairment | 3/97 (3.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Migraine | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Monoparesis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Nervous system disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Neuropathy peripheral | 16/97 (16.5%) | 22/102 (21.6%) | 12/37 (32.4%) | |||
| Neurotoxicity | 9/97 (9.3%) | 3/102 (2.9%) | 0/37 (0%) | |||
| Paraesthesia | 7/97 (7.2%) | 15/102 (14.7%) | 5/37 (13.5%) | |||
| Paraparesis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Peripheral motor neuropathy | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Peripheral sensory neuropathy | 2/97 (2.1%) | 5/102 (4.9%) | 4/37 (10.8%) | |||
| Polyneuropathy | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Presyncope | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Psychomotor hyperactivity | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Sciatica | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Sleep phase rhythm disturbance | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Somnolence | 2/97 (2.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Speech disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Spinal cord compression | 0/97 (0%) | 0/102 (0%) | 2/37 (5.4%) | |||
| Syncope | 2/97 (2.1%) | 4/102 (3.9%) | 1/37 (2.7%) | |||
| Tremor | 6/97 (6.2%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Psychiatric disorders | ||||||
| Abnormal dreams | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Aggression | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Agitation | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Anxiety | 7/97 (7.2%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Bradyphrenia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Confusional state | 4/97 (4.1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Delirium | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Depressed mood | 3/97 (3.1%) | 3/102 (2.9%) | 1/37 (2.7%) | |||
| Depression | 7/97 (7.2%) | 1/102 (1%) | 2/37 (5.4%) | |||
| Disorientation | 8/97 (8.2%) | 0/102 (0%) | 0/37 (0%) | |||
| Euphoric mood | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hallucination | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Insomnia | 6/97 (6.2%) | 12/102 (11.8%) | 1/37 (2.7%) | |||
| Listless | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Mental disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Mood swings | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Nervousness | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Personality change | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Restlessness | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Sleep disorder | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Renal and urinary disorders | ||||||
| Anuria | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Azotaemia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Bladder obstruction | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Bladder spasm | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Dysuria | 5/97 (5.2%) | 3/102 (2.9%) | 2/37 (5.4%) | |||
| Enuresis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Haematuria | 7/97 (7.2%) | 3/102 (2.9%) | 3/37 (8.1%) | |||
| Haemoglobinuria | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Hydronephrosis | 0/97 (0%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Incontinence | 2/97 (2.1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Micturition disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Micturition urgency | 1/97 (1%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Nephropathy toxic | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Nocturia | 8/97 (8.2%) | 9/102 (8.8%) | 4/37 (10.8%) | |||
| Pollakiuria | 5/97 (5.2%) | 4/102 (3.9%) | 2/37 (5.4%) | |||
| Polyuria | 4/97 (4.1%) | 0/102 (0%) | 2/37 (5.4%) | |||
| Proteinuria | 1/97 (1%) | 3/102 (2.9%) | 3/37 (8.1%) | |||
| Renal impairment | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Urethral stenosis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Urinary hesitation | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Urinary incontinence | 7/97 (7.2%) | 4/102 (3.9%) | 3/37 (8.1%) | |||
| Urinary retention | 7/97 (7.2%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Urinary tract disorder | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Urinary tract obstruction | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Urine flow decreased | 1/97 (1%) | 0/102 (0%) | 2/37 (5.4%) | |||
| Reproductive system and breast disorders | ||||||
| Gynaecomastia | 0/97 (0%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Pelvic discomfort | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Pelvic pain | 1/97 (1%) | 4/102 (3.9%) | 3/37 (8.1%) | |||
| Penile pain | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Perineal pain | 0/97 (0%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Prostatic pain | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Prostatitis | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Scrotal oedema | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Testicular pain | 0/97 (0%) | 2/102 (2%) | 0/37 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Chronic obstructive pulmonary disease | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Cough | 15/97 (15.5%) | 13/102 (12.7%) | 5/37 (13.5%) | |||
| Dry throat | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Dysphonia | 5/97 (5.2%) | 11/102 (10.8%) | 1/37 (2.7%) | |||
| Dyspnoea | 15/97 (15.5%) | 23/102 (22.5%) | 10/37 (27%) | |||
| Dyspnoea exertional | 4/97 (4.1%) | 3/102 (2.9%) | 3/37 (8.1%) | |||
| Epistaxis | 21/97 (21.6%) | 15/102 (14.7%) | 7/37 (18.9%) | |||
| Haemoptysis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hiccups | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypopnoea | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Hypoxia | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lower respiratory tract inflammation | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Lung infiltration | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Nasal congestion | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Nasal dryness | 2/97 (2.1%) | 3/102 (2.9%) | 0/37 (0%) | |||
| Oropharyngeal pain | 5/97 (5.2%) | 6/102 (5.9%) | 1/37 (2.7%) | |||
| Orthopnoea | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Pleural effusion | 0/97 (0%) | 1/102 (1%) | 2/37 (5.4%) | |||
| Pneumonitis | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Productive cough | 5/97 (5.2%) | 5/102 (4.9%) | 0/37 (0%) | |||
| Pulmonary embolism | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Rales | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Rhinalgia | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Rhinorrhoea | 8/97 (8.2%) | 5/102 (4.9%) | 2/37 (5.4%) | |||
| Sputum discoloured | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Tachypnoea | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Throat irritation | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Tonsillar hypertrophy | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Wheezing | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Alopecia | 46/97 (47.4%) | 51/102 (50%) | 17/37 (45.9%) | |||
| Blood blister | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Decubitus ulcer | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Dermatitis | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Dermatitis allergic | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Dry skin | 9/97 (9.3%) | 14/102 (13.7%) | 4/37 (10.8%) | |||
| Ecchymosis | 5/97 (5.2%) | 0/102 (0%) | 2/37 (5.4%) | |||
| Erythema | 8/97 (8.2%) | 10/102 (9.8%) | 2/37 (5.4%) | |||
| Hair colour changes | 0/97 (0%) | 1/102 (1%) | 1/37 (2.7%) | |||
| Hair disorder | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hyperhidrosis | 1/97 (1%) | 3/102 (2.9%) | 2/37 (5.4%) | |||
| Hyperkeratosis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Hypoaesthesia facial | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Intertrigo | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Macule | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Nail bed bleeding | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Nail bed disorder | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Nail discolouration | 2/97 (2.1%) | 2/102 (2%) | 0/37 (0%) | |||
| Nail discomfort | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Nail disorder | 7/97 (7.2%) | 15/102 (14.7%) | 7/37 (18.9%) | |||
| Nail toxicity | 6/97 (6.2%) | 6/102 (5.9%) | 0/37 (0%) | |||
| Night sweats | 1/97 (1%) | 3/102 (2.9%) | 1/37 (2.7%) | |||
| Onychalgia | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Onychoclasis | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Onycholysis | 4/97 (4.1%) | 6/102 (5.9%) | 1/37 (2.7%) | |||
| Onychomadesis | 1/97 (1%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Palmar-plantar erythrodysaesthesia syndrome | 3/97 (3.1%) | 1/102 (1%) | 0/37 (0%) | |||
| Petechiae | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Photosensitivity reaction | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Precancerous skin lesion | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Pruritus | 7/97 (7.2%) | 4/102 (3.9%) | 2/37 (5.4%) | |||
| Purpura | 3/97 (3.1%) | 0/102 (0%) | 2/37 (5.4%) | |||
| Rash | 9/97 (9.3%) | 7/102 (6.9%) | 2/37 (5.4%) | |||
| Rash vesicular | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Skin atrophy | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Skin discolouration | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Skin discomfort | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Skin disorder | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Skin exfoliation | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Skin fissures | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Skin fragility | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Skin irritation | 0/97 (0%) | 1/102 (1%) | 0/37 (0%) | |||
| Skin lesion | 1/97 (1%) | 0/102 (0%) | 3/37 (8.1%) | |||
| Skin toxicity | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Skin ulcer | 3/97 (3.1%) | 0/102 (0%) | 4/37 (10.8%) | |||
| Swelling face | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Urticaria | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Social circumstances | ||||||
| Denture wearer | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Surgical and medical procedures | ||||||
| Intermittent claudication | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
| Vascular disorders | ||||||
| Capillary fragility | 2/97 (2.1%) | 0/102 (0%) | 0/37 (0%) | |||
| Deep vein thrombosis | 2/97 (2.1%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Flushing | 3/97 (3.1%) | 8/102 (7.8%) | 1/37 (2.7%) | |||
| Haematoma | 5/97 (5.2%) | 2/102 (2%) | 1/37 (2.7%) | |||
| Hot flush | 1/97 (1%) | 6/102 (5.9%) | 0/37 (0%) | |||
| Hypertension | 3/97 (3.1%) | 4/102 (3.9%) | 2/37 (5.4%) | |||
| Hypotension | 8/97 (8.2%) | 5/102 (4.9%) | 1/37 (2.7%) | |||
| Intra-abdominal haematoma | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Orthostatic hypotension | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Pallor | 8/97 (8.2%) | 1/102 (1%) | 3/37 (8.1%) | |||
| Peripheral embolism | 0/97 (0%) | 0/102 (0%) | 1/37 (2.7%) | |||
| Phlebitis | 1/97 (1%) | 0/102 (0%) | 0/37 (0%) | |||
| Thrombosis | 1/97 (1%) | 1/102 (1%) | 0/37 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00313781
Other Study ID Numbers:
- A4021011
First Posted:
Apr 12, 2006
Last Update Posted:
Apr 11, 2013
Last Verified:
Mar 1, 2013