Adjuvant Leuprolide With or Without Docetaxel in High Risk Prostate Cancer After Radical Prostatectomy
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT00283062
Collaborator
(none)
228
17
4
60
13.4
0.2
Study Details
Study Description
Brief Summary
This is a prospective, multicenter, open-label, randomized phase III study in participants at high risk of recurrent prostate cancer after radical prostatectomy. The study will investigate
-
Treatment with docetaxel (TAXOTERE®) every three weeks (q3w) plus leuprolide acetate (ELIGARD®) versus leuprolide acetate alone (ELIGARD®)
-
Immediate treatment following prostatectomy versus deferred treatment at the time of relapse
Using a 2x2 factorial design participants will therefore be randomized to
-
Immediate adjuvant treatment with docetaxel plus leuprolide acetate (chemotherapy and hormonal therapy)
-
Immediate adjuvant treatment with leuprolide acetate alone (hormonal therapy)
-
Deferred treatment with docetaxel plus leuprolide acetate (chemotherapy and hormonal therapy)
-
Deferred treatment with leuprolide acetate alone (hormonal therapy)
Primary Objective:
- The primary objective of the study is to compare progression-free survival using a 2x2 factorial design
Secondary Objectives:
-
To compare the 5-year overall, cancer-specific and metastasis-free survival after systemic treatment between the groups
-
To compare the safety and tolerability between Docetaxel in combination with leuprolide acetate and leuprolide acetate alone.
-
To evaluate quality of life as measured by the FACT-P questionnaire.
Originally, 1696 participants were planned in the study (with 424 participants randomized to each arm). However, only a total of 211 participants completed the randomization procedure as of 26 September 2007. Thus, sanofi-aventis, in accordance with the Steering Committee, decided to stop the participant recruitment as of 26 September 2007. Participants who had already signed their Informed Consent (IC) before September 26, 2007 were allowed to enter the randomization if they met eligibility criteria. The final revised number of planned participants to be randomly assigned to the 4 treatment arms was 250, and 228 participants were actually randomized.
The final sample size did not allow all the statistical analyses to be conducted on efficacy data. Therefore, the protocol was amended to reflect the change in the plans for statistical analysis. The study was underpowered to serve as the basis for drawing conclusions regarding efficacy and quality of life (QoL) endpoints.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The study consisted of the following:
-
Randomization of eligible participants within 120 days of prostatectomy
-
For participants assigned to immediate therapy, a treatment period up to 18 months within 8 days of randomization
-
For participants assigned to deferred treatment, a treatment period up to 18 months after evidence of progression prior to December 2010. Participants who did not progress before December 2010 were withdrawn from the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
228 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-Label, Randomized, Phase III Trial Comparing Immediate Adjuvant Hormonal Therapy (ELIGARD®- Leuprolide Acetate) in Combination With TAXOTERE® (Docetaxel) Administered Every Three Weeks Versus Hormonal Therapy Alone Versus Deferred Therapy Followed by the Same Therapeutic Options in Patients With Prostate Cancer at High Risk of Relapse After Radical Prostatectomy
Study Start Date
:
Dec 1, 2005
Actual Primary Completion Date
:
Dec 1, 2010
Actual Study Completion Date
:
Dec 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) Participants administered docetaxel every three weeks (q3w) for 6 cycles in combination with leuprolide acetate every 3 months for 18 months immediately following prostatectomy. |
Drug: Docetaxel (TAXOTERE®) Chemotherapy
75 mg/m^2 docetaxel administered intravenously over 1 hour on Day 1 every three weeks (q3w) for 6 cycles. The first cycle was to be administered within 8 days after randomization.
Corticosteroid pre-medication was mandatory. The following schedule was recommended - 8 mg Dexamethasone orally for 6 doses given - the night before chemotherapy, the morning of chemotherapy, 1 hour before docetaxel infusion, the night of chemotherapy, the morning of the day after chemotherapy and the night of the day after chemotherapy.
Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
22.5 mg leuprolide acetate injection administered subcutaneously (SC) every 3 months for 18 months. The first injection was to be administered within 8 days after randomization.
|
| Active Comparator: Leuprolide Acetate - Immediate Treatment (I-HT) Participants administered leuprolide acetate every 3 months for 18 months immediately following prostatectomy. |
Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
22.5 mg leuprolide acetate injection administered subcutaneously (SC) every 3 months for 18 months. The first injection was to be administered within 8 days after randomization.
|
| Experimental: Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with docetaxel every three weeks (q3w) for 6 cycles in combination with leuprolide acetate every 3 months for 18 months. |
Drug: Docetaxel (TAXOTERE®) Chemotherapy
75 mg/m^2 docetaxel administered IV over 1 hour on Day 1 q3w for 6 cycles. The first cycle was to be administered within 30 days after progression was confirmed.
Corticosteroid pre-medication was mandatory. The following schedule was recommended - 8 mg Dexamethasone orally for 6 doses given - the night before chemotherapy, the morning of chemotherapy, 1 hour before docetaxel infusion, the night of chemotherapy, the morning of the day after chemotherapy and the night of the day after chemotherapy.
Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
22.5 mg leuprolide acetate injection administered subcutaneously (SC) every 3 months for 18 months. The first injection was to be administered within 30 days after progression is confirmed (on Day 1 of docetaxel administration).
|
| Active Comparator: Leuprolide Acetate - Deferred Treatment (D-HT) Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with with leuprolide acetate every 3 months for 18 months. |
Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
22.5 mg leuprolide acetate injection administered subcutaneously (SC) every 3 months for 18 months. The first injection was to be administered within 30 days after progression is confirmed.
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression [from the date of surgery up to 3 years after randomization of the last participant]
PFS is the interval from the date of surgery to date of progression. The date of progression was the earlier of first PSA increase to ≥ 0.4 ng/mL confirmed within two weeks date of the nadir, if PSA nadir did not reach < 0.4 ng/mL (for deferred arm) first radiological/ histological evidence of tumor progression death. Median PFS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Median PFS could not be estimated. Reported is the number of participants with disease progression.
Secondary Outcome Measures
- Median Overall Survival (OS) [from the date of surgery up to 3 years after randomization of the last participant]
Overall survival (OS) was the time interval from the date of surgery to the date of death due to any cause. Median OS was to be estimated using Kaplan-Meier Curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Moreover, median OS could not be estimated. Reported is the number of participants who died from any cause.
- Median Cancer-specific Survival (CSS) [from the date of surgery up to 3 years after randomization of the last participant]
The CSS was the time from the date of surgery to the date of death due to prostate cancer. Median CSS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Therefore, based on a protocol amendment, median CSS was not estimated.
- Median Metastasis-free Survival (MFS) [from the date of surgery up to 3 years after randomization of the last participant]
MFS was the interval from the date of surgery to the date of the first clinical evidence of metastasis after treatment initiation. Metastasis was evaluated by a physical exam or radiologically on bone scan or CT scan. Local (palpable) progression, documented histologically or by imaging techniques was considered evidence of progression. Median MFS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Therefore, based on a protocol amendment, median MFS was not estimated.
- To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire [from 30 days before randomization (baseline) and 18 months after treatment initiation (for change from baseline)]
The FACT-P is 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 are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better QoL with fewer symptoms. A score of 156 represents the best outcome. Note: Enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn due to the low sample size.
- Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE) [from treatment initiation up to 19 months after treatment initiation]
Number of participants with treatment-emergent adverse events (TEAE). A TEAE was as any adverse event that occurred or worsened during the on-treatment period, which was the period from the day of first infusion of study treatment until 30 days after the last infusion of study treatment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Participants who met all of the following criteria were considered for enrollment into the study.
-
Pathologically confirmed adenocarcinoma of the prostate based on central pathology review. All other variants are excluded
-
Randomization should occur less than 120 days after prostatectomy AND lymphadenectomy.
-
A predicted probability of 5-year freedom from progression ≤ 60%, as determined by the postoperative nomogram developed by M. Kattan.
-
Bone-scan without evidence of metastasis (within 6 months of randomization)
-
Chest x-ray without evidence of metastasis (within 6 months of randomization)
-
Abdominal computed tomography (CT) Scan without evidence of metastasis (within 6 months of randomization)
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
-
Hematology evaluation within 2 weeks prior to randomization:
-
Neutrophils ≥ 2,000/mm3
-
Hemoglobin ≥ 10 g/dL
-
Platelets ≥ 100,000/mm3
-
Hepatic and renal function evaluation within 2 weeks prior to randomization:
-
Serum creatinine ≤1.5 × Upper normal limit (UNL) for the institution. If serum creatinine is > 1.5 × UNL, calculate creatinine clearance (should be ≥ 60ml/minute).
-
Total serum bilirubin ≤ UNL for the institution. Participants with Gilbert's syndrome may be eligible if indirect serum bilirubin levels at the time of randomization and, at least 6 month prior to randomization, confirm this condition (i.e. elevated indirect serum bilirubin).
-
Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamic pyruvic transaminase (SGPT) ≤ 1.5 × institutional UNL if alkaline phosphatase is ≤ UNL OR
-
alkaline phosphatase ≤ 5 × UNL if SGOT and SGPT are ≤ UNL
-
Prostate Specific Antigen (PSA) evaluation within 9 months prior to prostatectomy. However, a 120-day timeframe is recommended
-
Post operative PSA necessary for eligibility is defined as a level ≤ 0.2ng/mL using a standard assay at least 30 days after radical prostatectomy and within 7 days prior to randomization. Note that randomization should occur within 120 days after radical prostatectomy
-
Serum testosterone ≥ 150ng/dL within 6 months prior to randomization.
Exclusion Criteria:
Participants presenting with any of the following will not be included in the study.
-
Prior systemic treatment for prostate cancer with hormonal therapy, chemotherapy, or any other anticancer therapy.
-
Prior radiation therapy.
-
Participants who received, are receiving or scheduled to receive post-operative radiotherapy.
-
Participants taking alternative therapies for cancer must stop taking these therapies prior to randomization. Alternative therapies are not allowed during the treatment or follow-up portions of the study. This includes (but is not limited to) alternative therapies such as :
-
PC-SPES (all types)
-
5-alpha reductase inhibitors
-
Bisphosphonates are to be stopped prior to randomization and are not allowed during the study.
-
Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose ( ≤ 20 mg methylprednisolone per day or equivalent).
-
History of a malignancy other than prostate cancer. Exceptions to these criteria include:
-
participants with adequately treated non-melanoma skin cancers, and
-
participants with a history of another malignancy that was curatively treated (including participants with superficial bladder cancer) and who have not had evidence of disease for a minimum of 5 years.
-
Peripheral neuropathy ≥ Grade 2.
-
Electrocardiogram (ECG) with significant abnormalities (as determined by the investigator) within 90 days prior to randomization.
-
Participants who are medically unstable, including but not limited to active infection, acute hepatitis, gastrointestinal bleeding, uncontrolled cardiac arrhythmias, interstitial lung disease, inflammatory bowel disease, uncontrolled angina, uncontrolled hypercalcemia, uncompensated congestive heart failure, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome.
-
Participants with history of hypersensitivity to polysorbate 80.
-
Participants with a known history of viral hepatitis (B, C).
The above information was not intended to contain all considerations relevant to potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sanofi-Aventis Administrative Office | Bridgewater | New Jersey | United States | 08807 |
| 2 | Sanofi-Aventis Administrative Office | Macquarie Park | Australia | ||
| 3 | Sanofi-Aventis Administrative Office | Vienna | Austria | ||
| 4 | Sanofi-Aventis Administrative Office | Sao Paulo | Brazil | ||
| 5 | Sanofi-Aventis Administrative Office | Québec | Canada | ||
| 6 | Sanofi-Aventis Administrative Office | Paris | France | ||
| 7 | Sanofi-Aventis Administrative Office | Frankfurt | Germany | ||
| 8 | Sanofi-Aventis Administrative Office | Mumbai | India | ||
| 9 | Sanofi-Aventis Administrative Office | Natanya | Israel | ||
| 10 | Sanofi-Aventis Administrative Office | Milan | Italy | ||
| 11 | Sanofi-Aventis Administrative Office | Col. Coyoacan | Mexico | ||
| 12 | Sanofi-Aventis Administrative Office | PE Gouda | Netherlands | ||
| 13 | Sanofi-Aventis Administrative Office | Warsaw | Poland | ||
| 14 | Sanofi-Aventis Administrative Office | Moscow | Russian Federation | ||
| 15 | Sanofi-Aventis Administrative Office | Gauteng | South Africa | ||
| 16 | Sanofi-Aventis Administrative Office | Istanbul | Turkey | ||
| 17 | Sanofi-Aventis Administrative Office | Guildford Surrey | United Kingdom |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Jean-Philippe Aussel, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT00283062
Other Study ID Numbers:
- XRP6976J_3501
- EudraCT # : 2004-002203-32
- NCT00343967
First Posted:
Jan 27, 2006
Last Update Posted:
Jan 26, 2012
Last Verified:
Dec 1, 2010
Study Results
Participant Flow
| Recruitment Details | Originally, the study was planned for 1696 participants to be randomized. However, enrollment was not met and in September 2007, the Steering Committee decided to stop recruitment. Only participants who had signed Informed Consent by then and met eligibility criteria were randomized. 228 participants were randomized to this study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) |
|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. |
| Period Title: Overall Study | ||||
| STARTED | 55 | 55 | 56 | 62 |
| ADMINISTERED STUDY TREATMENT | 50 | 51 | 20 | 17 |
| COMPLETED HORMONAL THERAPY (6 Cycles) | 44 | 48 | 15 | 13 |
| COMPLETED CHEMOTHERAPY (6 Cycles) | 43 | 0 | 15 | 0 |
| COMPLETED | 43 | 48 | 15 | 13 |
| NOT COMPLETED | 12 | 7 | 41 | 49 |
Baseline Characteristics
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. | Total of all reporting groups |
| Overall Participants | 55 | 55 | 56 | 62 | 228 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
61.2
(7.4)
|
61.6
(7.0)
|
62.1
(7)
|
62.9
(7.5)
|
61.9
(7.2)
|
| Age, Customized (participants) [Number] | |||||
| <65 years |
37
67.3%
|
34
61.8%
|
35
62.5%
|
35
56.5%
|
141
61.8%
|
| >=65 years |
18
32.7%
|
21
38.2%
|
21
37.5%
|
27
43.5%
|
87
38.2%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
55
100%
|
55
100%
|
56
100%
|
62
100%
|
228
100%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||
| White |
48
87.3%
|
49
89.1%
|
43
76.8%
|
59
95.2%
|
199
87.3%
|
| Black |
6
10.9%
|
3
5.5%
|
7
12.5%
|
2
3.2%
|
18
7.9%
|
| Asian/Oriental |
0
0%
|
1
1.8%
|
4
7.1%
|
0
0%
|
5
2.2%
|
| Multiracial |
0
0%
|
0
0%
|
2
3.6%
|
0
0%
|
2
0.9%
|
| Other |
1
1.8%
|
2
3.6%
|
0
0%
|
1
1.6%
|
4
1.8%
|
Outcome Measures
| Title | Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression |
|---|---|
| Description | PFS is the interval from the date of surgery to date of progression. The date of progression was the earlier of first PSA increase to ≥ 0.4 ng/mL confirmed within two weeks date of the nadir, if PSA nadir did not reach < 0.4 ng/mL (for deferred arm) first radiological/ histological evidence of tumor progression death. Median PFS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Median PFS could not be estimated. Reported is the number of participants with disease progression. |
| Time Frame | from the date of surgery up to 3 years after randomization of the last participant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all randomized participants, regardless of whether or not they received any study drug. |
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) |
|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. |
| Measure Participants | 55 | 55 | 56 | 62 |
| Number [participants] |
10
18.2%
|
14
25.5%
|
9
16.1%
|
8
12.9%
|
| Title | Median Overall Survival (OS) |
|---|---|
| Description | Overall survival (OS) was the time interval from the date of surgery to the date of death due to any cause. Median OS was to be estimated using Kaplan-Meier Curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Moreover, median OS could not be estimated. Reported is the number of participants who died from any cause. |
| Time Frame | from the date of surgery up to 3 years after randomization of the last participant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all randomized participants, regardless of whether or not they received any drug. |
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) |
|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. |
| Measure Participants | 55 | 55 | 56 | 62 |
| Number [participants] |
0
0%
|
2
3.6%
|
1
1.8%
|
1
1.6%
|
| Title | Median Cancer-specific Survival (CSS) |
|---|---|
| Description | The CSS was the time from the date of surgery to the date of death due to prostate cancer. Median CSS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Therefore, based on a protocol amendment, median CSS was not estimated. |
| Time Frame | from the date of surgery up to 3 years after randomization of the last participant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Based on a protocol amendment, analysis for Median CSS was not to be performed as the study was underpowered. |
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) |
|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Median Metastasis-free Survival (MFS) |
|---|---|
| Description | MFS was the interval from the date of surgery to the date of the first clinical evidence of metastasis after treatment initiation. Metastasis was evaluated by a physical exam or radiologically on bone scan or CT scan. Local (palpable) progression, documented histologically or by imaging techniques was considered evidence of progression. Median MFS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Therefore, based on a protocol amendment, median MFS was not estimated. |
| Time Frame | from the date of surgery up to 3 years after randomization of the last participant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Based on a protocol amendment, analysis for Median MFS was not to be performed as the study was underpowered. |
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) |
|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire |
|---|---|
| Description | The FACT-P is 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 are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better QoL with fewer symptoms. A score of 156 represents the best outcome. Note: Enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn due to the low sample size. |
| Time Frame | from 30 days before randomization (baseline) and 18 months after treatment initiation (for change from baseline) |
Outcome Measure Data
| Analysis Population Description |
|---|
| QoL population: The subset of randomized participants who had an evaluable baseline questionnaire and at least one evaluable post-baseline questionnaire. A baseline QoL questionnaire was considered evaluable if it was filled out within 30 days prior to randomization, and no later than the date of randomization. |
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) |
|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. |
| Measure Participants | 40 | 48 | 15 | 15 |
| Baseline |
124.0
(6.0)
|
121.5
(17.8)
|
114.7
(13.9)
|
119.7
(15.8)
|
| Change from Baseline (N=33, N=41, N=12, N=10) |
0.7
(12.6)
|
1.7
(17.2)
|
6.7
(15.9)
|
6.1
(18.9)
|
| Title | Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE) |
|---|---|
| Description | Number of participants with treatment-emergent adverse events (TEAE). A TEAE was as any adverse event that occurred or worsened during the on-treatment period, which was the period from the day of first infusion of study treatment until 30 days after the last infusion of study treatment. |
| Time Frame | from treatment initiation up to 19 months after treatment initiation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population: all randomized participants who received any study drug |
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) |
|---|---|---|---|---|
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. |
| Measure Participants | 50 | 51 | 20 | 17 |
| with any adverse event (AE) |
47
85.5%
|
48
87.3%
|
19
33.9%
|
14
22.6%
|
| with any serious adverse event (SAE) |
12
21.8%
|
8
14.5%
|
5
8.9%
|
2
3.2%
|
| with an SAE resulting in death |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| with a drug-related AE |
47
85.5%
|
43
78.2%
|
18
32.1%
|
10
16.1%
|
| with a drug-related SAE |
6
10.9%
|
0
0%
|
2
3.6%
|
0
0%
|
| with AE leading to discontinue all study therapy |
2
3.6%
|
0
0%
|
1
1.8%
|
0
0%
|
| with AE leading to chemotherapy discontinuation |
1
1.8%
|
NA
NaN
|
1
1.8%
|
NA
NaN
|
| with AE leading to chemotherapy dose reduction |
5
9.1%
|
NA
NaN
|
2
3.6%
|
NA
NaN
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) | ||||
| Arm/Group Description | Participants administered 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 75 mg/m^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months. | Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with 22.5 mg leuprolide acetate every 3 months for 18 months. | ||||
All Cause Mortality |
||||||||
| Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/50 (24%) | 8/51 (15.7%) | 5/20 (25%) | 2/17 (11.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 3/50 (6%) | 0/51 (0%) | 2/20 (10%) | 0/17 (0%) | ||||
| Neutropenia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Cardiac disorders | ||||||||
| Coronary artery disease | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eye disorders | ||||||||
| Optic neuropathy | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Inguinal hernia | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Colitis | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Diarrhoea | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Haemorrhoidal haemorrhage | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hernial eventration | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Rectal haemorrhage | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| General disorders | ||||||||
| Pyrexia | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Extravasation | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Fatigue | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Oedema peripheral | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Diverticulitis | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Face injury | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Facial bones fracture | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Foot fracture | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Subdural haematoma | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Investigations | ||||||||
| Blood cholesterol increased | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Blood glucose increased | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Blood triglycerides increased | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthropathy | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Arthralgia | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Pain in extremity | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Respiratory tract neoplasm | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nervous system disorders | ||||||||
| Carpal tunnel syndrome | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Dizziness | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Transient ischaemic attack | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Renal colic | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Urinary incontinence | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | Leuprolide Acetate - Immediate Treatment (I-HT) | Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | Leuprolide Acetate - Deferred Treatment (D-HT) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/50 (94%) | 48/51 (94.1%) | 19/20 (95%) | 13/17 (76.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Lymphopenia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Cardiac disorders | ||||||||
| Palpitations | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Diastolic dysfunction | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nodal arrhythmia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Sinus tachycardia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Tachycardia | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| Phimosis | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Thalassaemia | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Deafness | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hearing impaired | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eye disorders | ||||||||
| Lacrimation increased | 4/50 (8%) | 0/51 (0%) | 2/20 (10%) | 0/17 (0%) | ||||
| Vision blurred | 4/50 (8%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eye pain | 2/50 (4%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Ocular hyperaemia | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Blepharitis | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Cataract | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Conjunctivitis | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eye haemorrhage | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eye pruritus | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eyelid oedema | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Glaucoma | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Keratoconjunctivitis sicca | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Lacrimal disorder | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Optic neuropathy | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Retinal detachment | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Retinopathy | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 16/50 (32%) | 4/51 (7.8%) | 4/20 (20%) | 1/17 (5.9%) | ||||
| Diarrhoea | 14/50 (28%) | 2/51 (3.9%) | 6/20 (30%) | 0/17 (0%) | ||||
| Constipation | 10/50 (20%) | 1/51 (2%) | 4/20 (20%) | 0/17 (0%) | ||||
| Stomatitis | 7/50 (14%) | 0/51 (0%) | 2/20 (10%) | 0/17 (0%) | ||||
| Dyspepsia | 5/50 (10%) | 1/51 (2%) | 2/20 (10%) | 0/17 (0%) | ||||
| Dry mouth | 3/50 (6%) | 1/51 (2%) | 2/20 (10%) | 1/17 (5.9%) | ||||
| Vomiting | 3/50 (6%) | 2/51 (3.9%) | 2/20 (10%) | 0/17 (0%) | ||||
| Inguinal hernia | 2/50 (4%) | 3/51 (5.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Abdominal pain | 2/50 (4%) | 1/51 (2%) | 1/20 (5%) | 1/17 (5.9%) | ||||
| Dysphagia | 2/50 (4%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Flatulence | 3/50 (6%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Gastrooesophageal reflux disease | 2/50 (4%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Abdominal discomfort | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Abdominal pain lower | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Buccal mucosal roughening | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Gastritis | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Mouth ulceration | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Rectal haemorrhage | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Toothache | 0/50 (0%) | 2/51 (3.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Abdominal distension | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Abdominal hernia | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Abdominal pain upper | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Anorectal discomfort | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Gastrointestinal haemorrhage | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Glossodynia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Haemorrhoids | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Oral discomfort | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Paraesthesia oral | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Sensitivity of teeth | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Sigmoiditis | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Tongue discolouration | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| General disorders | ||||||||
| Fatigue | 32/50 (64%) | 16/51 (31.4%) | 13/20 (65%) | 3/17 (17.6%) | ||||
| Oedema peripheral | 12/50 (24%) | 4/51 (7.8%) | 5/20 (25%) | 0/17 (0%) | ||||
| Asthenia | 5/50 (10%) | 3/51 (5.9%) | 5/20 (25%) | 1/17 (5.9%) | ||||
| Pyrexia | 5/50 (10%) | 2/51 (3.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Induration | 3/50 (6%) | 2/51 (3.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Mucosal inflammation | 4/50 (8%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Pain | 4/50 (8%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Chest discomfort | 3/50 (6%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Chest pain | 1/50 (2%) | 0/51 (0%) | 2/20 (10%) | 0/17 (0%) | ||||
| Influenza like illness | 2/50 (4%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Injection site reaction | 3/50 (6%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Chills | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Injection site pain | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Injection site swelling | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Localised oedema | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Tenderness | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Cyst | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Discomfort | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Extravasation | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Face oedema | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Infusion site extravasation | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Injection site discolouration | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Injection site discomfort | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Injection site erythema | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Injection site nodule | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Injection site rash | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Necrosis | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Nodule | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Temperature intolerance | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Thirst | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Immune system disorders | ||||||||
| Drug hypersensitivity | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Hypersensitivity | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Multiple allergies | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Infections and infestations | ||||||||
| Infection | 4/50 (8%) | 1/51 (2%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Bronchitis | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Sinusitis | 1/50 (2%) | 2/51 (3.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Herpes zoster | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Hordeolum | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nasopharyngitis | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Neutropenic infection | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Pharyngitis | 0/50 (0%) | 2/51 (3.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Rhinitis | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Upper respiratory tract infection | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Urinary tract infection | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Abscess | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Anal infection | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Campylobacter intestinal infection | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Cellulitis | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Erysipelas | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Escherichia urinary tract infection | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eye infection | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Gastroenteritis viral | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Genital infection fungal | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Herpes simplex | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Herpes simplex ophthalmic | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Influenza | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Lip infection | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Oral candidiasis | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Otitis externa | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Pyelonephritis | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Skin candida | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Tooth abscess | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Viral infection | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Foot fracture | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Procedural complication | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Contusion | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Excoriation | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Eye penetration | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Injury | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Nail avulsion | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Seroma | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Vascular injury | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Investigations | ||||||||
| Weight increased | 6/50 (12%) | 8/51 (15.7%) | 3/20 (15%) | 2/17 (11.8%) | ||||
| Blood glucose increased | 1/50 (2%) | 1/51 (2%) | 1/20 (5%) | 0/17 (0%) | ||||
| Weight decreased | 2/50 (4%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Blood urea increased | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Cardiac murmur | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Blood cholesterol increased | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Blood pressure increased | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Blood urine | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Body temperature fluctuation | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Bone density decreased | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Gamma-glutamyltransferase | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 4/50 (8%) | 2/51 (3.9%) | 2/20 (10%) | 0/17 (0%) | ||||
| Hyperglycaemia | 4/50 (8%) | 2/51 (3.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hypercholesterolaemia | 2/50 (4%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Increased appetite | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Diabetes mellitus | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Fluid retention | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Hypercalcaemia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hyperkalaemia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hypertriglyceridaemia | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Hypoglycaemia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 6/50 (12%) | 7/51 (13.7%) | 5/20 (25%) | 0/17 (0%) | ||||
| Back pain | 7/50 (14%) | 3/51 (5.9%) | 5/20 (25%) | 1/17 (5.9%) | ||||
| Pain in extremity | 9/50 (18%) | 4/51 (7.8%) | 2/20 (10%) | 1/17 (5.9%) | ||||
| Myalgia | 4/50 (8%) | 5/51 (9.8%) | 4/20 (20%) | 0/17 (0%) | ||||
| Muscle spasms | 2/50 (4%) | 2/51 (3.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Musculoskeletal pain | 1/50 (2%) | 3/51 (5.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Neck pain | 0/50 (0%) | 4/51 (7.8%) | 0/20 (0%) | 0/17 (0%) | ||||
| Arthritis | 1/50 (2%) | 1/51 (2%) | 1/20 (5%) | 0/17 (0%) | ||||
| Bone pain | 3/50 (6%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Osteoporosis | 1/50 (2%) | 2/51 (3.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Flank pain | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Groin pain | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Joint lock | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Joint stiffness | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Limb discomfort | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Muscle twitching | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Muscular weakness | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Musculoskeletal chest pain | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Osteoarthritis | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Osteopenia | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Keratoacanthoma | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Squamous cell carcinoma of skin | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nervous system disorders | ||||||||
| Dysgeusia | 17/50 (34%) | 0/51 (0%) | 5/20 (25%) | 0/17 (0%) | ||||
| Headache | 14/50 (28%) | 3/51 (5.9%) | 3/20 (15%) | 0/17 (0%) | ||||
| Peripheral sensory neuropathy | 12/50 (24%) | 2/51 (3.9%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Dizziness | 5/50 (10%) | 2/51 (3.9%) | 3/20 (15%) | 0/17 (0%) | ||||
| Paraesthesia | 6/50 (12%) | 1/51 (2%) | 2/20 (10%) | 0/17 (0%) | ||||
| Hypoaesthesia | 5/50 (10%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Neuropathy peripheral | 2/50 (4%) | 1/51 (2%) | 2/20 (10%) | 0/17 (0%) | ||||
| Ageusia | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Burning sensation | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Disturbance in attention | 2/50 (4%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Amnesia | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Aphasia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Carpal tunnel syndrome | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hyperaesthesia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hypogeusia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Lethargy | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Restless legs syndrome | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Sciatica | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Sensory loss | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Sinus headache | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Tremor | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 6/50 (12%) | 5/51 (9.8%) | 1/20 (5%) | 1/17 (5.9%) | ||||
| Depression | 3/50 (6%) | 3/51 (5.9%) | 2/20 (10%) | 1/17 (5.9%) | ||||
| Mood altered | 4/50 (8%) | 3/51 (5.9%) | 1/20 (5%) | 1/17 (5.9%) | ||||
| Libido decreased | 2/50 (4%) | 4/51 (7.8%) | 0/20 (0%) | 2/17 (11.8%) | ||||
| Anxiety | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Affect lability | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Claustrophobia | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Confusional state | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Emotional distress | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nervousness | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Sleep disorder | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Urinary incontinence | 15/50 (30%) | 14/51 (27.5%) | 0/20 (0%) | 2/17 (11.8%) | ||||
| Nocturia | 3/50 (6%) | 4/51 (7.8%) | 1/20 (5%) | 0/17 (0%) | ||||
| Pollakiuria | 2/50 (4%) | 6/51 (11.8%) | 0/20 (0%) | 0/17 (0%) | ||||
| Stress urinary incontinence | 1/50 (2%) | 3/51 (5.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Haematuria | 1/50 (2%) | 2/51 (3.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Dysuria | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Urinary retention | 1/50 (2%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Bladder pain | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Micturition urgency | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nephrolithiasis | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Renal cyst | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Terminal dribbling | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Ureteric stenosis | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Urethral obstruction | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Urinary tract disorder | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Erectile dysfunction | 15/50 (30%) | 17/51 (33.3%) | 1/20 (5%) | 1/17 (5.9%) | ||||
| Gynaecomastia | 0/50 (0%) | 2/51 (3.9%) | 2/20 (10%) | 0/17 (0%) | ||||
| Penile pain | 0/50 (0%) | 1/51 (2%) | 1/20 (5%) | 0/17 (0%) | ||||
| Ejaculation disorder | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Genital lesion | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nipple pain | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Oedema genital | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Perineal pain | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Testicular atrophy | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 6/50 (12%) | 1/51 (2%) | 3/20 (15%) | 0/17 (0%) | ||||
| Cough | 3/50 (6%) | 2/51 (3.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Hiccups | 5/50 (10%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Epistaxis | 4/50 (8%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Oropharyngeal pain | 3/50 (6%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Bronchial obstruction | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Chronic obstructive pulmonary disease | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Dry throat | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nasal congestion | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nasal discomfort | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Nasal disorder | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Pulmonary embolism | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Rales | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Rhinitis allergic | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 29/50 (58%) | 0/51 (0%) | 9/20 (45%) | 0/17 (0%) | ||||
| Nail disorder | 14/50 (28%) | 0/51 (0%) | 6/20 (30%) | 0/17 (0%) | ||||
| Rash | 6/50 (12%) | 2/51 (3.9%) | 4/20 (20%) | 0/17 (0%) | ||||
| Hyperhidrosis | 7/50 (14%) | 3/51 (5.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Dry skin | 7/50 (14%) | 1/51 (2%) | 1/20 (5%) | 0/17 (0%) | ||||
| Nail discolouration | 3/50 (6%) | 0/51 (0%) | 2/20 (10%) | 0/17 (0%) | ||||
| Night sweats | 2/50 (4%) | 0/51 (0%) | 1/20 (5%) | 1/17 (5.9%) | ||||
| Pruritus | 2/50 (4%) | 2/51 (3.9%) | 0/20 (0%) | 0/17 (0%) | ||||
| Dermatitis | 0/50 (0%) | 2/51 (3.9%) | 1/20 (5%) | 0/17 (0%) | ||||
| Eczema | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 1/17 (5.9%) | ||||
| Onychomadesis | 0/50 (0%) | 0/51 (0%) | 2/20 (10%) | 0/17 (0%) | ||||
| Blister | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Dermal cyst | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Dermatitis contact | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Erythema | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Erythema multiforme | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Exfoliative rash | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
| Hair disorder | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hair growth abnormal | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hyperkeratosis palmaris and plantaris | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Onychoclasis | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Pain of skin | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Rash erythematous | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Skin disorder | 1/50 (2%) | 0/51 (0%) | 0/20 (0%) | 0/17 (0%) | ||||
| Urticaria | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Vascular disorders | ||||||||
| Hot flush | 36/50 (72%) | 38/51 (74.5%) | 11/20 (55%) | 8/17 (47.1%) | ||||
| Hypertension | 6/50 (12%) | 2/51 (3.9%) | 2/20 (10%) | 0/17 (0%) | ||||
| Flushing | 4/50 (8%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Hypotension | 1/50 (2%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Intermittent claudication | 0/50 (0%) | 1/51 (2%) | 0/20 (0%) | 0/17 (0%) | ||||
| Peripheral coldness | 0/50 (0%) | 0/51 (0%) | 1/20 (5%) | 0/17 (0%) | ||||
| Venous insufficiency | 0/50 (0%) | 0/51 (0%) | 0/20 (0%) | 1/17 (5.9%) | ||||
Limitations/Caveats
The study had difficulties in meeting enrollment goals within a reasonable time frame. The final sample size allowed for the safety analyses but was underpowered for drawing conclusions regarding efficacy and quality of life (QoL) endpoints.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The investigator shall provide the Steering Committee a copy of any manuscript, abstract or oral communication derived from the study for review and comment at least 30 days in advance of any submission. The Sponsor's representatives shall have the right to review and/or delay any publication or presentation to prevent disclosure of Sponsor's confidential information and preserve intellectual property rights.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | |
| Contact-Us@sanofi.com |
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT00283062
Other Study ID Numbers:
- XRP6976J_3501
- EudraCT # : 2004-002203-32
- NCT00343967
First Posted:
Jan 27, 2006
Last Update Posted:
Jan 26, 2012
Last Verified:
Dec 1, 2010