Clinical Trial Results:
An open, single dose, antitumor effect study of 2-hydroxyflutamide as a controlled release product (Liproca® Depot), injected into the prostate in patients with localized prostate cancer.
|
Summary
|
|
EudraCT number |
2011-001137-16 |
Trial protocol |
SE FI |
Global end of trial date |
05 Nov 2015
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
03 Jun 2016
|
First version publication date |
03 Jun 2016
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
LPC-003
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02341404 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
LIDDS AB
|
||
Sponsor organisation address |
Virdings allé 32b, Uppsala, Sweden, 75450
|
||
Public contact |
Monica Wallter, LIDDS AB, 46 (0)737070922, monica.wallter@liddspharma.com
|
||
Scientific contact |
Carl-Gustaf Gölander, LIDDS AB, 46 (0)761354354, carl-gustaf.golander@liddspharma.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
18 Aug 2015
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
05 Nov 2015
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To characterize and to quantify the histopathologhical changes in the surgical specimens obtained in patients undergoing prostatectomy in addition to imaging changes (MRI) following a single injection of Liproca® Depot in patients with localized prostate cancer.
|
||
Protection of trial subjects |
Patients were observered in the clinics during the study visits. Physical examination and vital signs were taken at study start and end of study, while blood samples for Clinical Chemistry and hematology were taken at all visits. These safety lab data were continuously reviewed by PI for changes and abnormalities.
|
||
Background therapy |
None. | ||
Evidence for comparator |
No comparator used. | ||
Actual start date of recruitment |
31 Aug 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Sweden: 13
|
||
Country: Number of subjects enrolled |
Finland: 10
|
||
Worldwide total number of subjects |
23
|
||
EEA total number of subjects |
23
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
10
|
||
From 65 to 84 years |
13
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
The study contains two parts; Part I First Patient Visit 09 MAY 2912, Last Patient Visit 17 JUL 2013. After completion, an extention with Part II was done. Part II FPV 17 DEC 2014, LPV 18 MAY 2015. Two sites; Tampere University Hospital (Dept. of Surgery) and Uppsala University Hospital (Dept. of Urology) participated in both parts of the study. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
The study population was men, between 50 and 75 years, with localized prostate cancer (T1c,T2a-c; Gleason score equal to, or less than, 3+4; PSA less than 20 ng/ml), verified by biopsy with no previous or on-going hormone therapy for prostate cancer. 18 pts were enrolled for Part I and 5 pts for Part II. Part I: 600-2000 mg Part II: 1800-2400 mg | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Inclusion
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
|
|||||||||
Blinding used |
Not blinded | |||||||||
Blinding implementation details |
This study was an open, Phase IIa, non-randomized, multicentre study (2 sites).
|
|||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Baseline (Part I- 15vol% Liproca per ml prostate) | |||||||||
Arm description |
Part I of the study, were the planned dose was 600-2000 mg 2-HOF and 6 weeks follow-up until prostatectomy. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Liproca Depot
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
2-hydroxyflutamide (2-HOF)
|
|||||||||
Pharmaceutical forms |
Powder and solution for solution for injection
|
|||||||||
Routes of administration |
Intraprostatic use
|
|||||||||
Dosage and administration details |
The formulation consists of two sterile Components, one aqueous liquid (Liproca Diluent) and a dry powder, containing the active drug pre-filled in a mixer container (Liproca Powder). The two components are, prior to injection, mixed under aspetic conditions to a paste, which will be transfered to a syringe, and administrated with injection into the prostate.
For Part I, a dose of 600-2000 mg 2-HOF was planned as single dose (corresponding to 3-10 ml ready-mixed paste). When decidingthe total and individual dose to be injected, the total prostate volume, number of foci and total tumour volume were taken into consideration in each patient. The individual dosing strategy was developed based on information from biopsies and imaging. Guieline was 1.5 ml of ready-mixed paste per 10 ml prostate volume, with a maximum amount of 10 ml prepared paste totally.
Local injection of ready-mixed paste, administrated via rectum and with ultrasound guidance, in and around major tumour foci.
|
|||||||||
|
Arm title
|
Baseline (Part II - 30vol% Liproca per ml prostate)) | |||||||||
Arm description |
Part II of the study, where the planned dose was 1800-2400 mg 2-HOF and 8 weeks follow-up until prostatectomy. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Liproca Depot
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
2-hydroxyflutamide (2-HOF)
|
|||||||||
Pharmaceutical forms |
Powder and solution for solution for injection
|
|||||||||
Routes of administration |
Intraprostatic use
|
|||||||||
Dosage and administration details |
The formulation consists of two sterile Components, one aqueous liquid (Liproca Diluent) and a dry powder, containing the active drug pre-filled in a mixer container (Liproca Powder). The two components are, prior to injection, mixed under aspetic conditions to a paste, which will be transfered to a syringe, and administrated with injection into the prostate.
For Part II, the target dose of Liproca Depot was 1800-2400 mg corresponding to approximately 30% of the prostate volume. When deciding the individual dose to be injected, the total prostate volumem number of tumour foci and total tumour volume were taken into consideration in each patient. If tumour were found in both lobes, the distribution of paste shoule be related to the amount of tumour in each lobe.
Local injection of ready-mixed paste, administrated via rectum and with ultrasound guidance, in and around major tumour foci.
|
|||||||||
|
||||||||||
|
Period 2
|
||||||||||
Period 2 title |
Treatment
|
|||||||||
Is this the baseline period? |
No | |||||||||
Allocation method |
Not applicable
|
|||||||||
Blinding used |
Not blinded | |||||||||
Blinding implementation details |
N/A
|
|||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Treatment 6 weeks (Part I - 15vol% Liproca/ml prostate) | |||||||||
Arm description |
Part I of the study, were the planned dose was 600-2000 mg 2-HOF and 6 weeks follow-up until prostatectomy. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Liproca Depot
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
2-hydroxyflutamide (2-HOF)
|
|||||||||
Pharmaceutical forms |
Powder and solution for solution for injection
|
|||||||||
Routes of administration |
Intraprostatic use
|
|||||||||
Dosage and administration details |
The formulation consists of two sterile Components, one aqueous liquid (Liproca Diluent) and a dry powder, containing the active drug pre-filled in a mixer container (Liproca Powder). The two components are, prior to injection, mixed under aspetic conditions to a paste, which will be transfered to a syringe, and administrated with injection into the prostate.
For Part I, a dose of 600-2000 mg 2-HOF was planned as single dose (corresponding to 3-10 ml ready-mixed paste). When decidingthe total and individual dose to be injected, the total prostate volume, number of foci and total tumour volume were taken into consideration in each patient. The individual dosing strategy was developed based on information from biopsies and imaging. Guieline was 1.5 ml of ready-mixed paste per 10 ml prostate volume, with a maximum amount of 10 ml prepared paste totally.
Local injection of ready-mixed paste, administrated via rectum and with ultrasound guidance, in and around major tumour foci.
|
|||||||||
|
Arm title
|
Treatment 8 weeks (Part II- 30vol% Liproca/ml prostate) | |||||||||
Arm description |
Part II of the study, where the planned dose was 1800-2400 mg 2-HOF and 8 weeks follow-up until prostatectomy. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Liproca Depot
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
2-hydroxyflutamide (2-HOF)
|
|||||||||
Pharmaceutical forms |
Powder and solution for solution for injection
|
|||||||||
Routes of administration |
Intraprostatic use
|
|||||||||
Dosage and administration details |
The formulation consists of two sterile Components, one aqueous liquid (Liproca Diluent) and a dry powder, containing the active drug pre-filled in a mixer container (Liproca Powder). The two components are, prior to injection, mixed under aspetic conditions to a paste, which will be transfered to a syringe, and administrated with injection into the prostate.
For Part II, a target dose of 1800-2400 mg 2-HOF corresponding to approximately 30% of the prostate volume was planned as single dose. When deciding the total and individual dose to be injected, the total prostate volume, number of foci and total tumour volume were taken into consideration in each patient. If tumours were found in both lobes, the distibution of paste should be related to the amount of tumour in each lobe.
Administration was done by local injection of ready-mixed paste via rectum and with ultrasound guidance, in and around major tumour foci.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Baseline (Part I- 15vol% Liproca per ml prostate)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Part I of the study, were the planned dose was 600-2000 mg 2-HOF and 6 weeks follow-up until prostatectomy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Baseline (Part II - 30vol% Liproca per ml prostate))
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Part II of the study, where the planned dose was 1800-2400 mg 2-HOF and 8 weeks follow-up until prostatectomy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Baseline (Part I- 15vol% Liproca per ml prostate)
|
||
Reporting group description |
Part I of the study, were the planned dose was 600-2000 mg 2-HOF and 6 weeks follow-up until prostatectomy. | ||
Reporting group title |
Baseline (Part II - 30vol% Liproca per ml prostate))
|
||
Reporting group description |
Part II of the study, where the planned dose was 1800-2400 mg 2-HOF and 8 weeks follow-up until prostatectomy. | ||
Reporting group title |
Treatment 6 weeks (Part I - 15vol% Liproca/ml prostate)
|
||
Reporting group description |
Part I of the study, were the planned dose was 600-2000 mg 2-HOF and 6 weeks follow-up until prostatectomy. | ||
Reporting group title |
Treatment 8 weeks (Part II- 30vol% Liproca/ml prostate)
|
||
Reporting group description |
Part II of the study, where the planned dose was 1800-2400 mg 2-HOF and 8 weeks follow-up until prostatectomy. | ||
|
||||||||||||||||
End point title |
Histopathological changes - Visible nucleoli [1] | |||||||||||||||
End point description |
Visible nucleoli was unchanged in non-affected tumour tissue at last visit compared to Baseline (Day 1).
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
End of Study Visit compared to baseline (Day 1).
|
|||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
||||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||||||||
End point title |
Histopathological changes - Nucleus hyperchromasia [2] | |||||||||||||||
End point description |
Nucleus hyperchromasia (darker than normal staining pattern in the nucleus) was unchanged in non-affected tumour tissue at last visit compared to baseline (day 1).
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
End of Study visit compared to baseline (Day 1).
|
|||||||||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
||||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||
End point title |
Histopathological changes - Cytoplasm/nucleus ratio [3] | |||||||||
End point description |
A decreased cytoplasm/nucleus (C:N) ratio (i.e. increased nucleus/cytoplasm ratio) is commonly associated with precancerous dysplasia as well as with malignant cells.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
End of Study Visit compared to Day 1 (baseline).
|
|||||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
||||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Histopathological changes - Cytoplasmic clearing [4] | |||||||||
End point description |
||||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
End of Study visit compared to Day 1 (baseline)
|
|||||||||
| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
||||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Histological visual results - Histopathologic alterations [5] | |||||||||
End point description |
||||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
End of Study Visit compared to Day 1 (baseline).
|
|||||||||
| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
||||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
MRI visual results - MR changes global effect [6] | |||||||||
End point description |
||||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
End of Study Visit compared to (baseline).
|
|||||||||
| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
||||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
MRI visual results - MR changes tumour effect [7] | |||||||||
End point description |
||||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
End of Study Visit compared to baseline.
|
|||||||||
| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
||||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||||||||||||||
End point title |
Apparent diffusion coefficient (ADC) in index lesion by MRI [8] | ||||||||||||||||||||
End point description |
Apparent diffusion coefficient (ADC) measures the magnitude of water diffusion within tissue. An increased value for ADC indicates an anti-androgen effect, as a decreased cell density in tumour tissue results in an increased magnitude of water diffusion.
Images for measuring ADC was collected at baseline (Day 1) and End of Study (after 6 or 8 weeks), both in index lesion (site of main tumour in prostate) and in non-index lesion (other sites of tumour tissue in prostate).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
End of Study Visit compared to Day 1 (baseline).
|
||||||||||||||||||||
| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Apparent diffusion coefficient (ADC) in non-index lesion by MRI [9] | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
End of Study Visit compared to Day 1 (baseline).
|
||||||||||||||||||||
| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||
End point title |
Size of index lesion by MRI [10] [11] | ||||||||||||
End point description |
Only descriptive data available from Part I of the study.
The median size of index lesion in the prostate for 13 measurable patient was 1.40 cm (length), 0.90 cm (width) and 1.20 m (height).
There were only 4 patients who had measurements also at week 6, none showed a significant change of the tumour size.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
End of Study Visit (6 weeks) compared to Day 1 (baseline).
|
||||||||||||
| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was done for the study. Only descriptive results available. [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data has only been reported for patients in Part II. No summary results available. |
|||||||||||||
|
|||||||||||||
Attachments |
MRI index tumour MRI index tumour - post treatment |
||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||
End point title |
Histological visual results - Stroma reduction/cell clustering [12] | ||||||
End point description |
|||||||
End point type |
Primary
|
||||||
End point timeframe |
End of Study Visit compared to Day 1 (baseline).
Only done for Part II: The patients were followed for 8 weeks after injection and until prostatectomy was done.
|
||||||
| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was added to Part II after completion of Part I, hence no data available for patients in Part I. |
|||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||
End point title |
(Cho+PA+Cr)/Cit spectral intensity ratio - 2D MRSI | ||||||||||||||||||||
End point description |
Intraprostatic tumour growth is associated with increased cell membrane turnover and increased cell proliferation, which lead to altered relative concentrations of certain metabolities included creatine (Cr), choline (Cho), polyamines (PA) and citrate (Cit), most specifically an increase in choline and a decrease in citrate. The effect of Liproca Depot was assessed by quantification of (Cho+PA+Cr)/Cit before treatment (baseline) and after treatment (week 6, or week 8).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
End of Study Visit compared to Day 1 (baseline).
|
||||||||||||||||||||
|
|||||||||||||||||||||
| Notes [13] - Only site Uppsala |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||
End point title |
(Cho+PA+Cr)/Cit spectral intensity ratio - Single-voxel MRS [14] | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of Study Visit (6 weeks) compared to Day 1 (baseline).
Only done for Part I.
|
||||||||||||
| Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data has only been reported as comments to each patient in Part II. No summary results available. |
|||||||||||||
|
|||||||||||||
| Notes [15] - Only site Uppsala |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
(Cho+PA+Cr)/H20 spectral intensity ratio [16] | ||||||||||||
End point description |
The variables (Cho+PA+Cr)/H20 spectral intensity ratio and Cit/H2O spectral intensity ratio before and after treatment were added as a complement to the variable (Cho+PA+Cr)/Cit . The difference in (Cho+PA+Cr)/Cit may be difficult to evalute if the Cit and PA concentrations decrease close to the noise level, the Cho concentration increases and the Cr concentration change is small. The H2O concentration is not expected to change before and after treatment, why changes in these ratios may be reliable.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of Study Visit (week 6) compared to Day 1 (baseline).
Done only for Part I.
|
||||||||||||
| Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data has only been reported as comments to each patient in Part II. No summary results available. |
|||||||||||||
|
|||||||||||||
| Notes [17] - Only site Uppsala |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Cit/H2O spectral intensity ratio [18] | ||||||||||||
End point description |
The variables (Cho+PA+Cr)/H20 spectral intensity ratio and Cit/H2O spectral intensity ratio before and after treatment were added as a complement to the variable (Cho+PA+Cr)/Cit . The difference in (Cho+PA+Cr)/Cit may be difficult to evalute if the Cit and PA concentrations decrease close to the noise level, the Cho concentration increases and the Cr concentration change is small. The H2O concentration is not expected to change before and after treatment, why changes in these ratios may be reliable.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
End of Study Visit (week 6) compared to Day 1 (baseline).
Done only for Part I.
|
||||||||||||
| Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data has only been reported as comments to each patient in Part II. No summary results available. |
|||||||||||||
|
|||||||||||||
| Notes [19] - Only site Uppsala |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||
End point title |
Plasma PSA | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
For Part I: Baseline (Day 1) and End of Study Visit (week 6)
For Part II: Baseline (Day 1) and End of Study Visit (week 8)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: Figure 3. PSA % change from baseline.PNG) |
||||||||||||||||||||
| Notes [20] - End of Study [21] - End of Study |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Changes in prostate volume | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline (Day 1) compared to 4 weeks (only Part I) and End of Study (6 weeks or 8 weeks).
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: Figure 4. Prostate volume - change in % from baseline.PNG) |
||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters harmonized - Tmax | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters harmonized - Cmax | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters harmonized - T last | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters harmonized - AUC all | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters harmonized - AUC 7d | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters harmonized - AUC 28d | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters harmonized - AUC 42d | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters observed - Tmax | ||||||||
End point description |
Safety variable. Data reported calculated based on the original scheduled time points.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters observed - Cmax | ||||||||
End point description |
Safety variable. Data reported calculated on the actual time points when plasma samples were taken.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters observed - T last | ||||||||
End point description |
Safety variable. Data reported calculated on the actual time points when plasma samples were taken.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacokinetic parameters observed - AUC all | ||||||||
End point description |
Safety variable. Data reported calculated on the actual time points when plasma samples were taken.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Only for Part I: Pharmacokinetic samples were summarized for samples taken at baseline (Day 1), after 7 days, 28 days and at end of study (week 6).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first patient visit in Part I: 09 MAY 2012 until last patient visit Part II: 18 MAY 2015.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part I: 18 patients
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Part I of the study, were the planned dose was 600-2000 mg 2-HOF and 6 weeks follow-up until prostatectomy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part II: 5 patients
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Part II of the study, where the planned dose was 1600-2400 mg 2-HOF and 8 weeks follow-up until prostatectomy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
07 Mar 2011 |
Amendment 1: The substantial change in the amendment was that if a biopsy at diagnosis was not performed as described in the protocol, another biopsy using the biopsy mapping described should be taken approximately 6 weeks before the first MRI. There were also some non-substantial changes, e.g. time between first MRI and day of injection, removal of questionnaire, emphasis on noting the correct dosing when injecting both lobes and volume blood in sample for PK. |
||
12 May 2014 |
Amendment 2: The extension of the study with another 10 patients at a higher dosage of Liproca (up to 2 400 mg), and a time period of 6 - 8 weeks between the Liproca administration and the prostatectomy was described in the second amendment. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
