Efficacy and Safety of Longidaze in the Treatment of Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia (ADAM)

A Multicenter, Randomized, Parallel, Controlled, Prospective, Open-label Study of the Efficacy and Safety of Longidaze Lyophilisate for Solution for Injections and Rectal Suppositories 3,000 IU in the Combined Treatment of Patients With Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia

The goal of this clinical trial is to learn if Longidaze works to treat lower urinary tract symptoms in adult males with benign prostatic hyperplasia. It will also learn about the safety of Longidaze. The main question it aims to answer is:

• Does addition of Longidaze to tamsulosin lower the severity of symptoms assessed by International Prostate Symptom Score?
• What medical problems do participants have under the combined treatment by Longidaze and tamsulosin?

Researchers will compare combined therapy (Longidaze + tamsulosin) with monotherapy (tamsulosin only) to see if the combination works better.

Participants will:

• Take tamsulosin (0.4mg) every day for 130 days
• In combined therapy arm -- make intramuscular injections of Longidaze every 5 days (5 injections); then apply Longidaze rectal suppositories every 3 days (10 applications); then apply Longidaze rectal suppositories every 7 days (10 applications)
• Visit the clinic on day 1, 26±1, 60±1, 130±3 for checkups and tests

Study Overview

• Status: Completed
• Conditions: Lower Urinary Tract Symptoms; Prostatic Hyperplasia
• Intervention / Treatment: Drug: bovhyaluronidase azoximer; Drug: tamsulosin

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russia
  • Krasnodar, Russia, 350000
    • LLC "Krasnodar Medical and Biological Center"
  • Saint Petersburg, Russia, 197022
    • First Saint Petersburg State Medical University named after academician I.P. Pavlov
  • Yaroslavl, Russia, 150001
    • LLC "Clinic of Modern Medicine of Dr. Bogorodskaya"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed Written Informed Consent Form for participation in the study.
2. Male outpatients aged 40 years or older.
3. Presence of lower urinary tract symptoms due to BPH at least 6 months prior to the screening visit.
4. Symptom severity according to the International Prostate Symptom Score (IPSS) ≥ 8 at the screening visit.
5. Negative urethral smear (PCR) test for chlamydia, gonorrhea, trichomoniasis, mycoplasmosis and ureaplasmosis performed no earlier than 1 month prior to study inclusion.
6. Negative blood test (ELISA) for syphilis performed no earlier than 1 month prior to study inclusion.
7. Maximum urine flow rate (Qmax) based on uroflowmetry results during screening is ≥5 ml/sec; residual urine volume during screening is up to 150 ml.
8. Consent to follow the effective methods of contraception specified in the protocol throughout the study.

Exclusion Criteria:

1. History of hypersensitivity to the study drug, background therapy drug or their components or intolerance thereof.
2. Patients who require or do not wish to stop taking drugs prohibited before or during the study.
3. Contraindications to the study therapy at the time of screening: acute infectious diseases; pulmonary hemorrhage and hemoptysis; fresh vitreous hemorrhage.
4. Hematuria, hematological diseases, oncological diseases, chronic heart failure class III-IV according to the New York Heart Association system, diabetes mellitus, chronic renal failure, hypogonadism in the history.
5. Acute prostatitis at the time of screening and/or within 4 weeks before screening.
6. Symptoms of urinary tract infection at the time of screening and/or within 4 weeks before the screening visit.
7. Need for planned surgical treatment of BPH and/or any other concomitant disease within 5 months from the screening visit.
8. History of prostatectomy, transurethral resection and/or other surgical interventions on the prostate gland, bladder or pelvic organs.
9. Neurogenic dysfunction of the bladder, congenital anomalies of the genitourinary system, sclerosis of the bladder neck, bladder diverticula, urolithiasis, bladder cancer or other bladder diseases in the medical history.
10. History of urethral stricture.
11. History of spinal injury.
12. Prostate-specific antigen (PSA) level >4 ng/ml at the screening visit or according to laboratory tests performed no more than 4 weeks before inclusion in the study.
13. History of acute urinary retention.
14. Use of any antibacterial drugs (except topical drugs) within 2 months before the screening visit.
15. Use of any medications for the treatment of LUTS/BPH before the study, including herbal preparations containing extracts of Serenoa repens and Pygeum Africanum.
16. History of orthostatic hypotension.
17. Patients with significant liver dysfunction at the screening visit: total bilirubin >2 ULN, albumin <35 g/L, prothrombin time >3 ULN.
18. Patients with significant renal dysfunction at the screening visit (blood creatinine >2 ULN), and / or patients on dialysis and / or patients with a history of kidney transplant.
19. The patient is scheduled for cataract or glaucoma surgery within 5 months after screening.
20. The presence of sexually transmitted diseases at the time of screening.
21. Patients with positive blood test results for HIV and/or hepatitis B and/or hepatitis C, performed no earlier than 1 month before the screening visit, or at the screening.
22. Decompensated diabetes mellitus (blood glucose and/or HbAc1 grade 3 or higher according to the used CTCAE 4.03 classifier);
23. Severe CNS diseases, including a history of seizures or conditions that may lead to their development; stroke or transient ischemic attack within 12 months before screening; traumatic brain injury or cases of loss of consciousness within 12 months before screening; brain tumor
24. Patients with mental disorders such as psychosis, manic-depressive disorders, chronic depression.
25. Acute or chronic gastric and/or duodenal ulcer at the time of screening.
26. History of alcoholism, drug addiction, drug abuse.
27. Participation in other interventional clinical trials of drugs less than 90 days before the screening visit.
28. Any conditions that, in the opinion of the Investigator, may interfere with the patients participation in the study, compliance with the procedures, or be contrary to his interests, as well as affect the results of the study.
29. Employees of the study center or the Sponsor company, their family members or subjects in dependent relationships.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tamsulosin	Drug: tamsulosin; Tamsulosin 0.4mg per os every day
Experimental: Longidaze + Tamsulosin	Drug: bovhyaluronidase azoximer; Longidaze 3000 IU intramuscularly once every 5 days with a course of 5 injections; Longidaze 3000 IU rectal suppositories once every 3 days with a course of 10 applications; Longidaze 3000 IU rectal suppositories once every 7 days with a course of 10 applications.; Other Names: Longidaze; Drug: tamsulosin; Tamsulosin 0.4mg per os every day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in IPSS Score on Day 60 and 130	Change in symptom severity assessed by the patient using the International Prostate Symptom Score (IPSS) relative to baseline on days 60 and 130 of therapy. IPSS score ranges from 0 to 35 with higher score representing more severe symptoms.	Day 0, Day 60, Day 130

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Qmax	Change in maximum urine flow rate (Qmax) according to uroflowmetry relative to baseline	Day 0, Day 26, Day 60, Day 130
Change from Baseline in Prostate Volume	Change in prostate volume relative to baseline	Day 0, Day 26, Day 60, Day 130
Change from Baseline in Residual Urine Volume	Change in residual urine volume based on ultrasound data relative to baseline	Day 0, Day 26, Day 60, Day 130
Change from Baseline in IPSS Score on Day 26	Change in symptom severity assessed by the patient using the International Prostate Symptom Score (IPSS) relative to baseline on day 26 of therapy. IPSS score ranges from 0 to 35 with higher score representing more severe symptoms.	Day 0, Day 26
Number of Participants with 4 Points and/or 25% Decrease in IPSS Score	Proportion of patients showing a decrease in symptom severity as assessed by the IPSS questionnaire by 4 or more points and/or by 25% from the baseline.	Day 0, Day 26, Day 60, Day 130
Change from Baseline in IPSS QoL Score	Change in quality of life (QoL) assessed by the patient using the International Prostate Symptom Score (IPSS, QoL domain) relative to baseline. IPSS QoL score ranges from 0 ("delighted") to 6 ("terrible").	Day 0, Day 26, Day 60, Day 130
Change from Baseline in IPSS-V Score	Change in voiding symptom severity assessed by the patient using the IPSS questionnaire (IPSS-V subscore) relative to baseline. IPSS-V score ranges from 0 to 20 with higher score representing more severe symptoms.	Day 0, Day 26, Day 60, Day 130
Change from Baseline in IPSS-S Score	Change in storage symptom severity assessed by the patient using the IPSS questionnaire (IPSS-S subscore) relative to baseline. IPSS-S score ranges from 0 to 15 with higher score representing more severe symptoms.	Day 0, Day 26, Day 60, Day 130
Change from Baseline in NIH-CPSI Score	Change in symptom severity according to the NIH Chronic Prostatitis Symptom index (NIH-CPSI) questionnaire relative to the baseline	Day 0, Day 26, Day 60, Day 130

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-Related Adverse Events	Safety assessment based on laboratory test data, evaluation of the vital signs, physical examination, and registration of adverse events.	From enrollment to the end of treatment on Day 130

Collaborators and Investigators

• Sponsor: NPO Petrovax
• Investigators: Principal Investigator: Pavel I. Rasner, University Clinic of the Scientific and Educational Institute of Clinical Medicine named after N.A. Semashko

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2023
• Primary Completion (Actual): February 9, 2024
• Study Completion (Actual): February 9, 2024

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 21, 2024
• First Posted (Actual): August 23, 2024

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Urological Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Prostatic Hyperplasia; Lower Urinary Tract Symptoms; Sulfur Compounds; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Benzene Derivatives; Benzenesulfonamides; Sulfonamides; Sulfones; Tamsulosin
• Other Study ID Numbers: LG-ADAM-23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No