Abiraterone Acetate Dose-Escalation Study in Hormone Refractory Prostate Cancer
Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00473746
Collaborator
(none)
66
3
2
78
22
0.3
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activities of abiraterone acetate (also referred to as CB7630) in patients with hormone refractory prostate cancer (HRPC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is an open-label (identity of assigned study drug will be known) study to evaluate the safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of what a drug does to the body), and anti-tumor activities of abiraterone acetate (also known as CB7630) in patients with HRPC. The study will be conducted in 2 phases (Phase 1 and Phase 2). In the first part of the study (Phase 1), the maximum tolerated dose (MTD) of abiraterone acetate will be determined for use in the second part of the study (Phase 2) where the number of patients who achieve at least a 50% decrease in prostate specific antigen (PSA) during treatment with abiraterone acetate will be assessed (MTD from Phase 1). Abiraterone acetate will be taken orally (by mouth) in fed and fasted patients once daily. Doses of abiraterone acetate (starting at 250 mg up to a maximum of 2000 mg) will be taken for 28-day treatment periods to determine the MTD. Patients will take MTD of abiraterone acetate for up to twelve 28 day cycles (12 months; patients will be given the option of staying on abiraterone acetate treatment if they are deriving benefit). In Phase 2, prednisone or dexamethasone will be administered concurrently with abiraterone acetate. Serial pharmacokinetic and pharmacodynamic samples will be collected and safety will be monitored throughout the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
66 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Open Label Dose Escalation Study of the 17α-Hydroxylase/ C17,20-Lyase Inhibitor, Abiraterone Acetate in Hormone Refractory Prostate Cancer
Study Start Date
:
Jun 1, 2006
Actual Primary Completion Date
:
Dec 1, 2012
Actual Study Completion Date
:
Dec 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I Dose Escalation
|
Drug: Abiraterone acetate
The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods , if no dose limiting toxicity (DLT) was documented at this dose, the dose will be escalated to next dose levels 500, 750, and 1000 mg/day. The dose escalation will continue to a maximum of 1000mg/day until Maximum Tolerated Dose (MTD) and a recommended Phase II dose was established.
|
| Experimental: Phase II Dose Treatment
|
Drug: Abiraterone acetate
Abiraterone acetate 1000 mg daily under fasted conditions upto 10 cycles of therapy.
Drug: prednisone/prednisolone or dexamethasone
prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) concurrent with abiraterone acetate
|
Outcome Measures
Primary Outcome Measures
- Phase 1: Maximum Tolerated Dose (MTD) of Abiraterone Acetate [Up to Cycle 12]
The MTD is the highest dose of a drug or treatment that does not cause unacceptable side effects.
- Phase 2: Participants With Greater Than or Equal to 50 Percent Decline in Prostate Specific Antigen (PSA) [Up to 12 weeks from start of treatment]
Number of participants with greater than or equal to 50 percent decrease in PSA levels were assessed. PSA decline was evaluated according to (Prostate Specific Antigen Working Group) PSAWG criteria. Decrease in PSA levels represented improvement.
Secondary Outcome Measures
- Phase 1: Maximum Plasma Concentration (Cmax) of Abiraterone Acetate [At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3.]
Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose).
- Phase 1: Time to Reach the Maximum Plasma Concentration (Tmax) of Abiraterone Acetate [At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3]
Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose)
- Phase 1: Area Under the Plasma-Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Abiraterone Acetate [At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3]
Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose).
- Phase 1: Area Under the Plasma-Concentration-time Curve From Time 0 to Infinite Time (AUCINF_obs) of Abiraterone Acetate [At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3]
Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose).
- Phase 1: Terminal Half-life (HL_Lambda_z) of Abiraterone Acetate [At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3]
Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose).
- Phase 1: Total Body Clearance (Cl_F_obs) of Abiraterone Acetate [At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3]
Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose).
- Phase 1: Volume of Distribution (Vz_F_obs) of Abiraterone Acetate [At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3]
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Volume of distribution is normally calculated by using equation volume of distribution =dose/initial concentration. Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose).
- Phase 2: Radiographic Progression Free Survival (RAD-PFS) [Up to 12 weeks from start of treatment]
RAD-PFS is the time interval from the date of first dose of abiraterone acetate therapy to the date of death or radiographic disease progression according to the RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Phase 2: PSA Progression Free Survival (PSA-PFS) [Up to 12 weeks from start of treatment]
PSA-PFS is the time interval from the date of first dose of abiraterone acetate therapy to the date of death or the PSA progression as defined by the Prostate Specific Antigen Working Group (PSAWG) criteria.
- Phase 2: Radiographic Objective Response Rate (RAD-ORR) [Up to 12 weeks from start of treatment]
The objective response rate is defined as the proportion of participants with measurable lesions achieving a Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Phase 2: Time to PSA Progression [Up to 12 weeks from start of treatment]
The time interval from the date of first dose of abiraterone acetate therapy to the date of the PSA progression as defined by the PSAWG criteria.
- Phase 2: Duration of PSA Response [Up to 12 weeks from start of treatment]
Duration of PSA response was defined as the duration between the date of confirmed PSA response and subsequent PSA progression date as defined by the PSAWG criteria.
- Phase 2: Participants With Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score [Up to 12 weeks from start of treatment]
ECOG performance status score ranges from 0 to 5 where 0=fully active, perform all pre-disease activities without restriction. 1=restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2=ambulatory, capable of self-care, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3=capable of limited self-care, confined to bed or chair >50% of waking hours. 4=completely disabled, not capable of any self-care, totally confined to bed or chair. 5=dead.
- Phase 2: Overall Survival [Up to Month 60]
Overall survival is the time interval from the date of first dose (cycle 1 day 1) of abiraterone acetate therapy to the date of death from any cause.
- Phase 2: Duration of Objective Response [Up to 12 weeks from start of treatment]
Duration of objective response was assessed only in participants who achieved a CR or PR, and measured from the first documented date of response to the first documented date of disease progression according to the RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Phase 1
-
Histologically confirmed adenocarcinoma of the prostate
-
No prior therapy with chemotherapy for prostate cancer
-
Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy
-
Testosterone <50 ng/dL
-
Progressive disease after androgen deprivation
-
The presence of objective metastatic disease is NOT required for study eligibility
-
Demonstrate disease progression after antiandrogen withdrawal
-
Eastern Cooperative Oncology Group (ECOG) performance status score = 0-1
-
Laboratory values within protocol-defined parameters
-
Systolic blood pressure <160 mmHg and diastolic blood pressure <110mmHg documented on at least 3 different days
-
Baseline adrenocorticotropic hormone (ACTH) stimulation test demonstrating a peak cortisol >18 µg/dL
-
Agrees to protocol-defined use of effective contraception
-
Life expectancy of >=12 weeks
Phase 2
-
Same as Phase 1 criteria with addition of following criteria
-
Neoadjuvant or adjuvant chemotherapy is only allowed if the last dose is >1 year from Cycle 1 Day 1
-
Target or non-target abnormalities must be present either on screening bone scan, computed tomography or magnetic resonance imaging
-
No prior treatment with ketoconazole for the management of androgen independent prostate cancer
Exclusion Criteria:
Phase 1
-
Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease prostate specific antigen (PSA) levels (eg, saw palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug
-
Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug
-
Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: conventional multivitamin supplements, selenium, lycopene, soy supplements
-
Prior radiation therapy completed <4 weeks prior to enrollment
-
Prior chemotherapy for hormone refractory prostate cancer
-
Any currently active second malignancy, other than non-melanoma skin cancer
-
Systolic blood pressure >=160 mmHg or diastolic blood pressure >=110 mmHg measured on at least 2 occasions
-
NYHA Class III or IV congestive heart failure
-
Myocardial infarction within the 6 months prior to the first dose of study drug
-
Serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled
-
Active psychiatric illnesses/social situations that would limit compliance with protocol requirements
-
Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
Phase 2
-
Same as phase 1 with the following addition
-
Abnormal electrocardiogram, including any finding which would interfere with assessment of intervals (patients with long QT syndrome, bundle branch blocks or hemiblocks are prohibited)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | San Francisco | California | United States | ||
| 2 | Boston | Massachusetts | United States | ||
| 3 | Houston | Texas | United States |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00473746
Other Study ID Numbers:
- CR016969
- COU-AA-002
First Posted:
May 15, 2007
Last Update Posted:
Apr 29, 2014
Last Verified:
Mar 1, 2014
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted between 10 July 2006 and 22 December 2012. |
|---|---|
| Pre-assignment Detail | 66 participants participated in the study, including 33 participants enrolled in Phase 1 of the study, and 33 participants enrolled in Phase 2 of the study. |
| Arm/Group Title | Phase 1 250 MG/DAY | Phase 1 500 MG/DAY | Phase 1 750 MG/DAY | Phase 1 1000 MG/DAY | Phase 2 1000 MG/DAY |
|---|---|---|---|---|---|
| Arm/Group Description | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate |
| Period Title: Period 1 (Phase 1) | |||||
| STARTED | 6 | 9 | 6 | 12 | 0 |
| COMPLETED | 0 | 0 | 0 | 2 | 0 |
| NOT COMPLETED | 6 | 9 | 6 | 10 | 0 |
| Period Title: Period 1 (Phase 1) | |||||
| STARTED | 0 | 0 | 0 | 0 | 33 |
| COMPLETED | 0 | 0 | 0 | 0 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 27 |
Baseline Characteristics
| Arm/Group Title | Phase 1 250 MG/DAY | Phase 1 500 MG/DAY | Phase 1 750 MG/DAY | Phase 1 1000 MG/DAY | Phase 2 1000 MG/DAY | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | Total of all reporting groups |
| Overall Participants | 6 | 9 | 6 | 12 | 33 | 66 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
66.7
(6.19)
|
67.6
(6.5)
|
73.2
(8.18)
|
72.9
(8.3)
|
70.3
(8.51)
|
70.3
(8.05)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
6
100%
|
9
100%
|
6
100%
|
12
100%
|
33
100%
|
66
100%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
6
100%
|
9
100%
|
6
100%
|
12
100%
|
33
100%
|
66
100%
|
Outcome Measures
| Title | Phase 1: Maximum Tolerated Dose (MTD) of Abiraterone Acetate |
|---|---|
| Description | The MTD is the highest dose of a drug or treatment that does not cause unacceptable side effects. |
| Time Frame | Up to Cycle 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received any study drug. MTD of abiraterone acetate was not reached because the doses administered appear to be well tolerated with no Dose Limiting Toxicity (DLT) even at 1000 milligram per day (mg/day [recommended maximum dose for phase 1]) and 1000 mg/day was taken as test dose in phase 2. |
| Arm/Group Title | Phase I Dose Escalation |
|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods , if no dose limiting toxicity (DLT) was documented at this dose, the dose will be escalated to next dose levels 500, 750, and 1000 mg/day. The dose escalation will continue to a maximum of 1000 mg/day until maximum tolerated dose (MTD) and a recommended Phase II dose was established. |
| Measure Participants | 33 |
| Number [mg/day] |
NA
(0)
|
| Title | Phase 2: Participants With Greater Than or Equal to 50 Percent Decline in Prostate Specific Antigen (PSA) |
|---|---|
| Description | Number of participants with greater than or equal to 50 percent decrease in PSA levels were assessed. PSA decline was evaluated according to (Prostate Specific Antigen Working Group) PSAWG criteria. Decrease in PSA levels represented improvement. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 33 |
| Confirmed |
26
433.3%
|
| Not Confirmed |
2
33.3%
|
| Total |
28
466.7%
|
| Title | Phase 1: Maximum Plasma Concentration (Cmax) of Abiraterone Acetate |
|---|---|
| Description | Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose). |
| Time Frame | At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase I Dose Escalation (250mg) | Phase I Dose Escalation (500mg) | Phase I Dose Escalation (750mg) | Phase I Dose Escalation (1000mg) |
|---|---|---|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods. | The second cohort was a abiraterone acetate 500 mg/day orally (by mouth), once daily for 28-day treatment periods. | The third cohort was a abiraterone acetate 700 mg/day orally (by mouth), once daily for 28-day treatment periods. | The fourth cohort was a abiraterone acetate 1000 mg/day orally (by mouth), once daily for 28-day treatment periods. |
| Measure Participants | 6 | 9 | 6 | 12 |
| Fasted |
283.000
(142.265)
|
330.633
(204.889)
|
289.533
(126.646)
|
509.500
(366.452)
|
| Fed |
421.000
(75.809)
|
676.000
(147.866)
|
1552.000
(458.082)
|
2194.250
(1096.914)
|
| Title | Phase 1: Time to Reach the Maximum Plasma Concentration (Tmax) of Abiraterone Acetate |
|---|---|
| Description | Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose) |
| Time Frame | At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase I Dose Escalation (250mg) | Phase I Dose Escalation (500mg) | Phase I Dose Escalation (750mg) | Phase I Dose Escalation (1000mg) |
|---|---|---|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods. | The second cohort was a abiraterone acetate 500 mg/day orally (by mouth), once daily for 28-day treatment periods. | The third cohort was a abiraterone acetate 700 mg/day orally (by mouth), once daily for 28-day treatment periods. | The fourth cohort was a abiraterone acetate 1000 mg/day orally (by mouth), once daily for 28-day treatment periods. |
| Measure Participants | 6 | 9 | 6 | 12 |
| Fasted |
2.000
(0.000)
|
1.500
(0.548)
|
2.033
(0.058)
|
1.833
(0.408)
|
| Fed |
2.044
(0.077)
|
2.667
(1.155)
|
2.000
(0.000)
|
4.000
(0.000)
|
| Title | Phase 1: Area Under the Plasma-Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Abiraterone Acetate |
|---|---|
| Description | Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose). |
| Time Frame | At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase I Dose Escalation (250mg) | Phase I Dose Escalation (500mg) | Phase I Dose Escalation (750mg) | Phase I Dose Escalation (1000mg) |
|---|---|---|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods. | The second cohort was a abiraterone acetate 500 mg/day orally (by mouth), once daily for 28-day treatment periods. | The third cohort was a abiraterone acetate 700 mg/day orally (by mouth), once daily for 28-day treatment periods. | The fourth cohort was a abiraterone acetate 1000 mg/day orally (by mouth), once daily for 28-day treatment periods. |
| Measure Participants | 6 | 9 | 6 | 12 |
| Fasted |
1329.178
(699.977)
|
1625.059
(930.364)
|
1565.659
(661.289)
|
3039.937
(1902.697)
|
| Fed |
1310.715
(311.041)
|
3624.781
(1041.927)
|
8920.790
(3060.457)
|
13695.482
(5623.185)
|
| Title | Phase 1: Area Under the Plasma-Concentration-time Curve From Time 0 to Infinite Time (AUCINF_obs) of Abiraterone Acetate |
|---|---|
| Description | Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose). |
| Time Frame | At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase I Dose Escalation (250mg) | Phase I Dose Escalation (500mg) | Phase I Dose Escalation (750mg) | Phase I Dose Escalation (1000mg) |
|---|---|---|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods. | The second cohort was a abiraterone acetate 500 mg/day orally (by mouth), once daily for 28-day treatment periods. | The third cohort was a abiraterone acetate 700 mg/day orally (by mouth), once daily for 28-day treatment periods. | The fourth cohort was a abiraterone acetate 1000 mg/day orally (by mouth), once daily for 28-day treatment periods. |
| Measure Participants | 6 | 9 | 6 | 12 |
| Fasted |
1411.268
(697.183)
|
1781.374
(986.770)
|
1665.454
(704.551)
|
3478.385
(2012.176)
|
| Fed |
1386.939
(290.240)
|
3839.804
(1080.853)
|
9358.743
(3338.601)
|
14404.387
(5971.041)
|
| Title | Phase 1: Terminal Half-life (HL_Lambda_z) of Abiraterone Acetate |
|---|---|
| Description | Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose). |
| Time Frame | At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase I Dose Escalation (250mg) | Phase I Dose Escalation (500mg) | Phase I Dose Escalation (750mg) | Phase I Dose Escalation (1000mg) |
|---|---|---|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods. | The second cohort was a abiraterone acetate 500 mg/day orally (by mouth), once daily for 28-day treatment periods. | The third cohort was a abiraterone acetate 700 mg/day orally (by mouth), once daily for 28-day treatment periods. | The fourth cohort was a abiraterone acetate 1000 mg/day orally (by mouth), once daily for 28-day treatment periods. |
| Measure Participants | 6 | 9 | 6 | 12 |
| Fasted |
5.284
(1.676)
|
10.591
(6.337)
|
7.066
(3.431)
|
14.361
(7.655)
|
| Fed |
5.125
(1.039)
|
6.913
(5.720)
|
7.939
(2.633)
|
12.454
(1.218)
|
| Title | Phase 1: Total Body Clearance (Cl_F_obs) of Abiraterone Acetate |
|---|---|
| Description | Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose). |
| Time Frame | At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase I Dose Escalation (250mg) | Phase I Dose Escalation (500mg) | Phase I Dose Escalation (750mg) | Phase I Dose Escalation (1000mg) |
|---|---|---|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods. | The second cohort was a abiraterone acetate 500 mg/day orally (by mouth), once daily for 28-day treatment periods. | The third cohort was a abiraterone acetate 700 mg/day orally (by mouth), once daily for 28-day treatment periods. | The fourth cohort was a abiraterone acetate 1000 mg/day orally (by mouth), once daily for 28-day treatment periods. |
| Measure Participants | 6 | 9 | 6 | 12 |
| Fasted |
4288.456
(1319.322)
|
5440.949
(4844.515)
|
1518.748
(822.714)
|
2649.954
(4617.049)
|
| Fed |
529.606
(99.532)
|
391.046
(99.118)
|
246.643
(72.970)
|
231.383
(97.746)
|
| Title | Phase 1: Volume of Distribution (Vz_F_obs) of Abiraterone Acetate |
|---|---|
| Description | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Volume of distribution is normally calculated by using equation volume of distribution =dose/initial concentration. Blood samples for pharmacokinetic (PK) measurements was taken on Day -7 at hour 0 (predose), at hours 1, 2, 4, 6, 8, and 12 (postdose). On Day -6 at 24 hour (postdose) and Day -5 at 48 hour (postdose). On Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 2 and 3 (Predose). |
| Time Frame | At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase I Dose Escalation (250mg) | Phase I Dose Escalation (500mg) | Phase I Dose Escalation (750mg) | Phase I Dose Escalation (1000mg) |
|---|---|---|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods. | The second cohort was a abiraterone acetate 500 mg/day orally (by mouth), once daily for 28-day treatment periods. | The third cohort was a abiraterone acetate 700 mg/day orally (by mouth), once daily for 28-day treatment periods. | The fourth cohort was a abiraterone acetate 1000 mg/day orally (by mouth), once daily for 28-day treatment periods. |
| Measure Participants | 6 | 9 | 6 | 12 |
| Fasted |
653.745
(447.316)
|
10252.077
(12268.787)
|
13688.367
(4265.429)
|
25494.398
(18670.215)
|
| Fed |
3940.400
(1275.408)
|
3418.280
(1934.384)
|
2739.655
(1084.694)
|
4068.885
(1462.613)
|
| Title | Phase 2: Radiographic Progression Free Survival (RAD-PFS) |
|---|---|
| Description | RAD-PFS is the time interval from the date of first dose of abiraterone acetate therapy to the date of death or radiographic disease progression according to the RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. RAD-PFS was not analyzed because of insufficient data to provide a meaningful estimate of the median and associated confidence interval (CI) |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 13 |
| Median (Full Range) [days] |
NA
|
| Title | Phase 2: PSA Progression Free Survival (PSA-PFS) |
|---|---|
| Description | PSA-PFS is the time interval from the date of first dose of abiraterone acetate therapy to the date of death or the PSA progression as defined by the Prostate Specific Antigen Working Group (PSAWG) criteria. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 33 |
| Median (95% Confidence Interval) [days] |
473
|
| Title | Phase 2: Radiographic Objective Response Rate (RAD-ORR) |
|---|---|
| Description | The objective response rate is defined as the proportion of participants with measurable lesions achieving a Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Thirteen evaluable participants with measurable disease at baseline were evaluated for radiographic objective response rate. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 13 |
| Confirmed |
9
150%
|
| Not Confirmed |
1
16.7%
|
| Title | Phase 2: Time to PSA Progression |
|---|---|
| Description | The time interval from the date of first dose of abiraterone acetate therapy to the date of the PSA progression as defined by the PSAWG criteria. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 33 |
| Median (95% Confidence Interval) [days] |
497
|
| Title | Phase 2: Duration of PSA Response |
|---|---|
| Description | Duration of PSA response was defined as the duration between the date of confirmed PSA response and subsequent PSA progression date as defined by the PSAWG criteria. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 33 |
| Median (95% Confidence Interval) [days] |
477
|
| Title | Phase 2: Participants With Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score |
|---|---|
| Description | ECOG performance status score ranges from 0 to 5 where 0=fully active, perform all pre-disease activities without restriction. 1=restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2=ambulatory, capable of self-care, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3=capable of limited self-care, confined to bed or chair >50% of waking hours. 4=completely disabled, not capable of any self-care, totally confined to bed or chair. 5=dead. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 33 |
| Baseline ECOG 0 |
20
333.3%
|
| Baseline ECOG 1 |
13
216.7%
|
| Baseline ECOG 2 |
0
0%
|
| Baseline ECOG 3 |
0
0%
|
| Baseline ECOG 4 |
0
0%
|
| Best Post-Baseline ECOG 0 |
28
466.7%
|
| Best Post-Baseline ECOG 1 |
5
83.3%
|
| Best Post-Baseline ECOG 2 |
0
0%
|
| Best Post-Baseline ECOG 3 |
0
0%
|
| Best Post-Baseline ECOG 4 |
0
0%
|
| Title | Phase 2: Overall Survival |
|---|---|
| Description | Overall survival is the time interval from the date of first dose (cycle 1 day 1) of abiraterone acetate therapy to the date of death from any cause. |
| Time Frame | Up to Month 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were enrolled into the study. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | Abiraterone acetate 1000 mg daily and concurrent prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) under fasted conditions upto 10 cycles of therapy. |
| Measure Participants | 33 |
| Median (95% Confidence Interval) [days] |
NA
|
| Title | Phase 2: Duration of Objective Response |
|---|---|
| Description | Duration of objective response was assessed only in participants who achieved a CR or PR, and measured from the first documented date of response to the first documented date of disease progression according to the RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Time Frame | Up to 12 weeks from start of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Thirteen evaluable participants with measurable disease at baseline were evaluated for radiographic duration of objective response. |
| Arm/Group Title | Phase II Dose Treatment |
|---|---|
| Arm/Group Description | The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods , if no dose limiting toxicity (DLT) was documented at this dose, the dose will be escalated to next dose levels 500, 750, and 1000 mg/day. The dose escalation will continue to a maximum of 1000 mg/day until maximum tolerated dose (MTD) and a recommended Phase II dose was established. |
| Measure Participants | 13 |
| Median (95% Confidence Interval) [days] |
NA
|
Adverse Events
| Time Frame | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Phase 1 250 MG/DAY | Phase 1 500 MG/DAY | Phase 1 750 MG/DAY | Phase 1 1000 MG/DAY | Phase 2 1000 MG/DAY | |||||
| Arm/Group Description | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | Abiraterone acetate | |||||
All Cause Mortality |
||||||||||
| Phase 1 250 MG/DAY | Phase 1 500 MG/DAY | Phase 1 750 MG/DAY | Phase 1 1000 MG/DAY | Phase 2 1000 MG/DAY | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Phase 1 250 MG/DAY | Phase 1 500 MG/DAY | Phase 1 750 MG/DAY | Phase 1 1000 MG/DAY | Phase 2 1000 MG/DAY | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 2/9 (22.2%) | 0/6 (0%) | 0/12 (0%) | 10/33 (30.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Cardiac disorders | ||||||||||
| Arrhythmia Supraventricular | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Myocardial Infarction | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Ventricular Extrasystoles | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| General disorders | ||||||||||
| Oedema Peripheral | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Pyrexia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Infections and infestations | ||||||||||
| Cystitis | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Device Related Infection | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Infection | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Urinary Tract Infection | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Urosepsis | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Investigations | ||||||||||
| Troponin Increased | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Hypokalaemia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Pathological Fracture | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Squamous Cell Carcinoma | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Syncope | 1/6 (16.7%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Renal and urinary disorders | ||||||||||
| Calculus Bladder | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Haematuria | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Renal Failure | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Urinary Bladder Haemorrhage | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Urinary Incontinence | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Urinary Retention | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Pulmonary Embolism | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Vascular disorders | ||||||||||
| Hypotension | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Phase 1 250 MG/DAY | Phase 1 500 MG/DAY | Phase 1 750 MG/DAY | Phase 1 1000 MG/DAY | Phase 2 1000 MG/DAY | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 9/9 (100%) | 6/6 (100%) | 12/12 (100%) | 33/33 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Lymphopenia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Neutropenia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Thrombocytopenia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Cardiac disorders | ||||||||||
| Atrial Fibrillation | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Palpitations | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Tachycardia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Cerumen Impaction | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Hypoacusis | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Endocrine disorders | ||||||||||
| Adrenal Insufficiency | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Gynaecomastia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 3/33 (9.1%) | |||||
| Eye disorders | ||||||||||
| Cataract | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Ocular Discomfort | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Ocular Hyperaemia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Visual Acuity Reduced | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal Discomfort | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 2/33 (6.1%) | |||||
| Abdominal Distension | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 1/33 (3%) | |||||
| Abdominal Pain | 1/6 (16.7%) | 2/9 (22.2%) | 2/6 (33.3%) | 2/12 (16.7%) | 3/33 (9.1%) | |||||
| Abdominal Pain Upper | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Constipation | 0/6 (0%) | 3/9 (33.3%) | 2/6 (33.3%) | 2/12 (16.7%) | 7/33 (21.2%) | |||||
| Defaecation Urgency | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Diarrhoea | 0/6 (0%) | 4/9 (44.4%) | 3/6 (50%) | 4/12 (33.3%) | 7/33 (21.2%) | |||||
| Dry Mouth | 0/6 (0%) | 2/9 (22.2%) | 2/6 (33.3%) | 1/12 (8.3%) | 2/33 (6.1%) | |||||
| Dyspepsia | 0/6 (0%) | 3/9 (33.3%) | 2/6 (33.3%) | 0/12 (0%) | 1/33 (3%) | |||||
| Flatulence | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Gastrointestinal Haemorrhage | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Gastrooesophageal Reflux Disease | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Gingival Pain | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Haematochezia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Lip Dry | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Nausea | 1/6 (16.7%) | 3/9 (33.3%) | 1/6 (16.7%) | 6/12 (50%) | 5/33 (15.2%) | |||||
| Rectal Haemorrhage | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Vomiting | 0/6 (0%) | 1/9 (11.1%) | 1/6 (16.7%) | 3/12 (25%) | 7/33 (21.2%) | |||||
| General disorders | ||||||||||
| Asthenia | 1/6 (16.7%) | 3/9 (33.3%) | 2/6 (33.3%) | 2/12 (16.7%) | 2/33 (6.1%) | |||||
| Chills | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Fatigue | 3/6 (50%) | 7/9 (77.8%) | 4/6 (66.7%) | 8/12 (66.7%) | 16/33 (48.5%) | |||||
| Irritability | 1/6 (16.7%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Mucosal Dryness | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Oedema | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Oedema Peripheral | 1/6 (16.7%) | 4/9 (44.4%) | 0/6 (0%) | 6/12 (50%) | 9/33 (27.3%) | |||||
| Pain | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Pyrexia | 0/6 (0%) | 1/9 (11.1%) | 1/6 (16.7%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Tenderness | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Thirst | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Hyperbilirubinaemia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 5/33 (15.2%) | |||||
| Infections and infestations | ||||||||||
| Infection | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Influenza | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Lower Respiratory Tract Infection | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Nasopharyngitis | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Tinea Versicolour | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Upper Respiratory Tract Infection | 1/6 (16.7%) | 1/9 (11.1%) | 1/6 (16.7%) | 1/12 (8.3%) | 5/33 (15.2%) | |||||
| Urinary Tract Infection | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 2/12 (16.7%) | 3/33 (9.1%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Contrast Media Reaction | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Contusion | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 3/12 (25%) | 5/33 (15.2%) | |||||
| Excoriation | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Fall | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Joint Sprain | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Muscle Injury | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Rib Fracture | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Skin Laceration | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Spinal Compression Fracture | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Investigations | ||||||||||
| Alanine Aminotransferase Increased | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 4/33 (12.1%) | |||||
| Aspartate Aminotransferase Increased | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 2/12 (16.7%) | 3/33 (9.1%) | |||||
| Blood Alkaline Phosphatase Increased | 1/6 (16.7%) | 0/9 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 2/33 (6.1%) | |||||
| Blood Bicarbonate Decreased | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Blood Creatinine Increased | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Platelet Count Decreased | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Weight Decreased | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Weight Increased | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| White Blood Cell Count Decreased | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Anorexia | 1/6 (16.7%) | 2/9 (22.2%) | 1/6 (16.7%) | 3/12 (25%) | 1/33 (3%) | |||||
| Decreased Appetite | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Dehydration | 0/6 (0%) | 1/9 (11.1%) | 2/6 (33.3%) | 0/12 (0%) | 0/33 (0%) | |||||
| Hyperchloraemia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Hyperglycaemia | 1/6 (16.7%) | 1/9 (11.1%) | 0/6 (0%) | 2/12 (16.7%) | 5/33 (15.2%) | |||||
| Hyperkalaemia | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 2/33 (6.1%) | |||||
| Hypernatraemia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 2/12 (16.7%) | 0/33 (0%) | |||||
| Hypoalbuminaemia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Hypoglycaemia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Hypokalaemia | 0/6 (0%) | 1/9 (11.1%) | 4/6 (66.7%) | 4/12 (33.3%) | 10/33 (30.3%) | |||||
| Hypomagnesaemia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 5/33 (15.2%) | |||||
| Hyponatraemia | 0/6 (0%) | 0/9 (0%) | 2/6 (33.3%) | 0/12 (0%) | 5/33 (15.2%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 1/6 (16.7%) | 1/9 (11.1%) | 2/6 (33.3%) | 2/12 (16.7%) | 9/33 (27.3%) | |||||
| Back Pain | 1/6 (16.7%) | 1/9 (11.1%) | 1/6 (16.7%) | 2/12 (16.7%) | 8/33 (24.2%) | |||||
| Bone Pain | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 10/33 (30.3%) | |||||
| Flank Pain | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Hypercreatinaemia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Muscle Fatigue | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Muscle Spasms | 0/6 (0%) | 1/9 (11.1%) | 1/6 (16.7%) | 0/12 (0%) | 6/33 (18.2%) | |||||
| Muscular Weakness | 2/6 (33.3%) | 1/9 (11.1%) | 2/6 (33.3%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Musculoskeletal Discomfort | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 2/12 (16.7%) | 1/33 (3%) | |||||
| Musculoskeletal Pain | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 5/33 (15.2%) | |||||
| Myalgia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Neck Pain | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Pain in Extremity | 0/6 (0%) | 0/9 (0%) | 2/6 (33.3%) | 0/12 (0%) | 4/33 (12.1%) | |||||
| Rotator Cuff Syndrome | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Tendonitis | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Basal Cell Carcinoma | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Squamous Cell Carcinoma | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Nervous system disorders | ||||||||||
| Aphasia | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Ataxia | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Dizziness | 0/6 (0%) | 1/9 (11.1%) | 2/6 (33.3%) | 3/12 (25%) | 7/33 (21.2%) | |||||
| Dizziness Postural | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Dysgeusia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Headache | 0/6 (0%) | 3/9 (33.3%) | 2/6 (33.3%) | 7/12 (58.3%) | 3/33 (9.1%) | |||||
| Lethargy | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Peripheral Sensory Neuropathy | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Transient Ischaemic Attack | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Confusional State | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 2/33 (6.1%) | |||||
| Depressed Mood | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Depression | 1/6 (16.7%) | 1/9 (11.1%) | 1/6 (16.7%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Euphoric Mood | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Insomnia | 1/6 (16.7%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Mood Altered | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Personality Change | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Stress | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Haematuria | 1/6 (16.7%) | 1/9 (11.1%) | 0/6 (0%) | 1/12 (8.3%) | 2/33 (6.1%) | |||||
| Micturition Urgency | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Nocturia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Pollakiuria | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 2/12 (16.7%) | 0/33 (0%) | |||||
| Urinary Incontinence | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Urinary Retention | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Urinary Tract Obstruction | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Pelvic Pain | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Testicular Pain | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 1/6 (16.7%) | 2/9 (22.2%) | 4/6 (66.7%) | 1/12 (8.3%) | 5/33 (15.2%) | |||||
| Dysphonia | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Dyspnoea | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 1/12 (8.3%) | 4/33 (12.1%) | |||||
| Epistaxis | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Nasal Congestion | 2/6 (33.3%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Pharyngolaryngeal Pain | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 1/33 (3%) | |||||
| Pleural Effusion | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Postnasal Drip | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Productive Cough | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Rales | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Rhinorrhoea | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Sinus Congestion | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/33 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Actinic Keratosis | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Dry Skin | 0/6 (0%) | 1/9 (11.1%) | 1/6 (16.7%) | 0/12 (0%) | 1/33 (3%) | |||||
| Ecchymosis | 0/6 (0%) | 0/9 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 8/33 (24.2%) | |||||
| Erythema | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 2/33 (6.1%) | |||||
| Hyperhidrosis | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Pruritus | 1/6 (16.7%) | 0/9 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/33 (3%) | |||||
| Rash | 0/6 (0%) | 0/9 (0%) | 0/6 (0%) | 0/12 (0%) | 4/33 (12.1%) | |||||
| Skin Hyperpigmentation | 0/6 (0%) | 1/9 (11.1%) | 1/6 (16.7%) | 0/12 (0%) | 0/33 (0%) | |||||
| Vascular disorders | ||||||||||
| Hot Flush | 0/6 (0%) | 2/9 (22.2%) | 2/6 (33.3%) | 3/12 (25%) | 10/33 (30.3%) | |||||
| Hypertension | 2/6 (33.3%) | 2/9 (22.2%) | 3/6 (50%) | 5/12 (41.7%) | 7/33 (21.2%) | |||||
| Hypotension | 1/6 (16.7%) | 2/9 (22.2%) | 0/6 (0%) | 0/12 (0%) | 3/33 (9.1%) | |||||
| Orthostatic Hypotension | 0/6 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/12 (0%) | 0/33 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Sr. Director, Clinical Research |
|---|---|
| Organization | Janssen R&D US |
| Phone | (310)914-2917 |
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00473746
Other Study ID Numbers:
- CR016969
- COU-AA-002
First Posted:
May 15, 2007
Last Update Posted:
Apr 29, 2014
Last Verified:
Mar 1, 2014