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Clinical Trial of Safety and Efficacy of Afalaza in Patients With Symptoms of Benign Prostatic Hyperplasia and Risk of Progression

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ClinicalTrials.gov Identifier: NCT01716104
Recruitment Status : Completed
First Posted : October 29, 2012
Results First Posted : October 8, 2018
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Materia Medica Holding

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Benign Prostatic Hyperplasia
Interventions Drug: Afalaza
Drug: Placebo
Enrollment 260

Recruitment Details  
Pre-assignment Details

Selection procedures were carried out after participant enrollment to determine whether the patient could participate in the study in accordance with the inclusion criteria.

Of the 260 patients enrolled, 11 did not meet inclusion criteria after screening procedures, they were not randomized.

Arm/Group Title Afalaza Placebo
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Afalaza (2 tablets twice a day) One tablet contains: affinity purified antibodies to endothelial nitric oxide synthase – 0.006g*, affinity purified antibodies to prostate-specific antigen – 0.006g*.

*applied onto isomalt crystals as a mixture of three active aqueous-alcoholic dilutions of the drug substance – diluted 100^12, 100^30, 100^50 times, respectively.

Excipients: lactose monohydrate; microcrystalline cellulose; magnesium stearate.

Placebo (2 tablets twice a day)
Period Title: Overall Study
Started 125 124
Completed 119 117
Not Completed 6 7
Reason Not Completed
Do not meet inclusion criteria             6             7
Arm/Group Title Afalaza Placebo Total
Hide Arm/Group Description Afalaza (2 tablets twice a day): Safety and Efficiency Placebo (2 tablets twice a day): Safety and Efficiency Total of all reporting groups
Overall Number of Baseline Participants 119 117 236
Hide Baseline Analysis Population Description
Intention to treat set
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 119 participants 117 participants 236 participants
54.3  (4.2) 54.4  (4.4) 54.4  (4.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 119 participants 117 participants 236 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
119
 100.0%
117
 100.0%
236
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 119 participants 117 participants 236 participants
Ukraine 1 3 4
Russia 118 114 232
1.Primary Outcome
Title Change in Total IPSS Scores (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline.
Hide Description The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.
Time Frame Baseline, 1, 3, 6 and 12 months
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ITT set
Arm/Group Title Afalaza Placebo
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Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Month 1 -1.3  (1.7) -0.6  (1.3)
Month 3 -2.3  (2.1) -1.5  (1.9)
Month 6 -3.0  (2.5) -1.9  (2.5)
Month 12 -3.7  (3.0) -2.9  (2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Change in Dynamics of Irritative Symptoms Evaluated by IPSS (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline
Hide Description

The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.

The sum of IPSS questions 2, 4, and 7 related to irritative symptoms. The total score of irritative symptoms can therefore range from 0 to 15 points (asymptomatic to very symptomatic).

Time Frame Baseline and 1, 3, 6, 12 months
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ITT set
Arm/Group Title Afalaza Placebo
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Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Month 1 -0.5  (0.9) -0.3  (1.1)
Month 3 -0.9  (1.2) -0.6  (1.2)
Month 6 -1.3  (1.5) -0.8  (1.4)
Month 12 -1.5  (1.6) -1.3  (1.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Secondary Outcome
Title Change in Maximum Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 1, 3, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
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ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: ml/s
Month 1 1.3  (3.2) 0.2  (2.6)
Month 3 1.5  (3.2) 0.7  (3.3)
Month 6 1.7  (3.2) 0.5  (2.7)
Month 12 2.5  (4.3) 1.4  (3.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
4.Secondary Outcome
Title Change in Average Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 1, 3, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: ml/s
Month 1 0.9  (2.0) 0.2  (1.9)
Month 3 1.3  (2.1) 0.7  (2.5)
Month 6 1.4  (2.0) 0.5  (2.2)
Month 12 1.4  (2.2) 0.6  (2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Percent Change in Mean Values of Prostate Gland Volume at 3, 6 and 12 Months Compared to Baseline
Hide Description Change in the volume of the prostate gland as a percentage of the baseline according to transrectal ultrasound
Time Frame Baseline and 3, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: percentage of prostate gland volume
Month 3 -6.6  (13.1) -2.9  (12.5)
Month 6 -10.0  (13.4) -4.9  (14.1)
Month 12 -11.8  (16.0) -6.5  (14.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
6.Secondary Outcome
Title Change in Mean Values of Micturition Volume at 3, 6 and 12 Months Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 3, 6 and 12 months
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ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: ml
Month 3 14.6  (105.0) 1.4  (76.8)
Month 6 27.5  (96.6) 5.0  (88.4)
Month 12 17.9  (106.0) 0.4  (71.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0437
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Change in the Mean Values of Residual Urine Volume at 3, 6 and 12 Months Compared to Baseline
Hide Description according to transabdominal ultrasound
Time Frame Baseline and 3, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: ml
Month 3 -6.5  (26.5) -0.9  (21.6)
Month 6 -8.8  (28.1) -4.3  (20.9)
Month 12 -8.0  (30.1) -3.5  (26.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0862
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
8.Secondary Outcome
Title Change in Quality of Life (QoL Index of IPSS) at 3, 6 and 12 Months Compared to Baseline
Hide Description Quality of life (QoL) Due to Urinary Symptoms is an eight point of the IPSS scale referred to the patient’s quality of life. The answers to this question range from “delighted” to “terrible” or 0 to 5.
Time Frame Baseline and 3, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Month 3 -0.4  (0.8) -0.4  (0.7)
Month 6 -0.7  (0.8) -0.5  (1.0)
Month 12 -1.0  (1.0) -0.6  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0621
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Change in Total Value of Risk Factors for Progression (Total Score of IPSS, Prostate Volume, PSA Level, Maximum Urinary Flow Rate, Residual Urine Volume) Compared to Baseline
Hide Description

To assess the risk of BPH progression, the following were used: 1) moderate to severe BPH symptoms (ie, IPSS total score> 7); 2) an increase in the volume of the prostate gland (> 30 cm^2); 3) increased PSA level in the blood (≥ 1.4 ng / ml); 4) a decrease in Qmax (<12 ml / s) and 5) a large volume of residual urine (> 200 ml).

The total value of risk factors for progression is assessed as the sum of the risk factors that the patient had at the time of inclusion in the study (presence of risk factors = 1 point, absence = 0 points). After 3, 6 and 12 months of treatment, the dynamics of risk factors for progression was assessed: an increase in the severity of the risk factor meant +1, no change = 0, a decrease in the severity of the risk factor of -1.

Time Frame Baseline and 3, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Mean (Standard Deviation)
Unit of Measure: Scores
Month 3 -0.9  (0.9) -0.7  (0.8)
Month 6 -0.7  (1.0) -0.4  (0.8)
Month 12 -1.0  (1.0) -0.6  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afalaza, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0142
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
10.Secondary Outcome
Title Number of Episodes of Acute Urinary Retention, Surgical Intervention During the Observation Period
Hide Description [Not Specified]
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT set
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description:
Afalaza (2 tablets twice a day): Safety and Efficacy
Placebo (2 tablets twice a day): Safety and Efficacy
Overall Number of Participants Analyzed 119 117
Measure Type: Number
Unit of Measure: episodes
0 0
Time Frame Adverse/Serious adverse events were registered during 12 months of therapy and 30 days after the end of the research
Adverse Event Reporting Description Adverse/Serious adverse events were registered in patients of the Full Analysis Set (n=249, Safety Population)
 
Arm/Group Title Afalaza Placebo
Hide Arm/Group Description Afalaza (2 tablets twice a day): Safety and Efficiency Placebo (2 tablets twice a day): Safety and Efficiency
All-Cause Mortality
Afalaza Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Afalaza Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/125 (0.00%)      1/124 (0.81%)    
Musculoskeletal and connective tissue disorders     
Arthralgia/Meniscus injury/Meniscus operation  1 [1]  0/125 (0.00%)  0 1/124 (0.81%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[1]
Resection of the medial meniscus and lateral meniscus. Resection of the mediapatulatory fold.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Afalaza Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/125 (20.00%)      29/124 (23.39%)    
Gastrointestinal disorders     
Epigastric pain  1  1/125 (0.80%)  0/124 (0.00%) 
Right-sided inguinal hernia  1  1/125 (0.80%)  0/124 (0.00%) 
Diarrhea  1  1/125 (0.80%)  0/124 (0.00%) 
Heartburn  1  0/125 (0.00%)  1/124 (0.81%) 
Swollen tongue  1  0/125 (0.00%)  1/124 (0.81%) 
Nausea  1  1/125 (0.80%)  2/124 (1.61%) 
Chronic gastritis, exacerbation  1  0/125 (0.00%)  1/124 (0.81%) 
General disorders     
Asthenia and Depressive weariness  1  0/125 (0.00%)  1/124 (0.81%) 
Infections and infestations     
Gastroenteritis  1  0/125 (0.00%)  1/124 (0.81%) 
Urinary tract infection  1  1/125 (0.80%)  0/124 (0.00%) 
Labial herpes  1  1/125 (0.80%)  0/124 (0.00%) 
Acute respiratory viral infection  1  9/125 (7.20%)  10/124 (8.06%) 
Acute bronchitis  1  1/125 (0.80%)  0/124 (0.00%) 
Rhinitis  1  0/125 (0.00%)  2/124 (1.61%) 
Pharyngitis  1  1/125 (0.80%)  0/124 (0.00%) 
Investigations     
Prostatic specific antigen increased  1  4/125 (3.20%)  6/124 (4.84%) 
Blood pressure increased  1  0/125 (0.00%)  1/124 (0.81%) 
Nervous system disorders     
Headache  1  1/125 (0.80%)  5/124 (4.03%) 
Respiratory, thoracic and mediastinal disorders     
Vasomotor rhinitis chronic, exacerbation  1  1/125 (0.80%)  0/124 (0.00%) 
Discomfort in the oropharynx  1  1/125 (0.80%)  0/124 (0.00%) 
Сough  1  1/125 (0.80%)  0/124 (0.00%) 
Skin and subcutaneous tissue disorders     
Allergic contact dermatitis  1  0/125 (0.00%)  1/124 (0.81%) 
Vascular disorders     
Hypertensive crisis  1  1/125 (0.80%)  1/124 (0.81%) 
Hypertensive crisis, accompanied by headache and nausea  1  1/125 (0.80%)  0/124 (0.00%) 
Chronic hemorrhoids, exacerbation  1  1/125 (0.80%)  0/124 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Mikhail Putilovskiy, MD, PhD, Director of Clinical Research and Medical Information
Organization: Materia Medica Holding
Phone: +74952761571 ext 302
Responsible Party: Materia Medica Holding
ClinicalTrials.gov Identifier: NCT01716104     History of Changes
Other Study ID Numbers: MMH-AZ-001-I
First Submitted: October 25, 2012
First Posted: October 29, 2012
Results First Submitted: July 17, 2017
Results First Posted: October 8, 2018
Last Update Posted: November 28, 2018