Phase III Randomized Study of Serenoa repens (Permixon) for Reducing Chronic Prostatic Inflammation and Re‑biopsy Need in Men with Benign Prostatic Hypertrophy.

Primary objective: assess whether a 12‑month course of Permixon® reduces the necessity for a repeat prostate biopsy, evaluated by downgrade of the PIRADS lesion on magnetic resonance imaging and/or a decrease in PSA concentration compared with placebo, thereby potentially limiting invasive diagnostic procedures in men with chronic prostate inflammation. Secondary objectives:

• Reduction of the entity of prostatic inflammation.
• Evaluation of improvements in urinary symptoms and overall quality of life, and assessment of the increased detection rate of clinically significant prostate cancer.

The trial enrolled male subjects aged 45 to 85 years presenting with lower urinary tract symptoms associated with Benign prostatic hypertrophy. Participants were required to have a total PSA >4 ng/mL and/or PIRADS ≥3 lesions on mpMRI, and to have undergone a prostate biopsy within four months of randomization confirming chronic non‑specific inflammation without prostate cancer. Selection was based on signed informed consent and compliance with ICH GCP and local regulations. No specific dietary, physical activity, or habit restrictions were described. The sponsor did not provide the total number of participants enrolled.

The SERENDIPITY study is a multicentric, randomized, placebo‑controlled phase III trial evaluating the effect of PERMIXON 160 mg (serenoa repens) on chronic prostate inflammation in men with Benign prostatic hypertrophy. Eligible participants are males aged 45–85 with lower urinary tract symptoms, a total PSA > 4 ng/mL and/or PIRADS ≥ 3 on mpMRI, and a histologically confirmed chronic non‑specific inflammation following a prostate biopsy performed within four months of randomization. After a screening visit to verify inclusion criteria and obtain informed consent, participants are randomized to receive either the active capsule or a matching placebo (Macrogol 6000) and commence a 12‑month treatment period. Follow‑up visits are scheduled to monitor PSA levels, MRI PIRADS scores, symptom questionnaires (IPSS, IIEF‑5, PINS), and safety parameters, with the primary assessment being the proportion of subjects undergoing a repeat prostate biopsy at 12 months. Secondary assessments include ln[PSA] at 12 months, PINS, PIRADS, lesion count, IS/IRANI scores, IPSS, IIEF‑5, and incidence of prostate cancer within the same timeframe. The end‑of‑study visit at month 12 completes the final evaluations. Participant involvement therefore extends for approximately one year, with the possibility of early discontinuation in the event of withdrawal of consent, medically indicated cessation, or significant protocol non‑compliance.

The investigational product is Permixon® 160 mg hard capsule containing the active botanical ingredient serenoa repens (bartram) small. The pharmaceutical form is a hard gelatin capsule administered orally. The dosing regimen consists of two capsules taken once daily, delivering a total daily dose of 320 mg of serenoa repens. Capsules are to be ingested with water in the morning, preferably on an empty stomach. Compliance is assessed by tablet count at each study visit and by patient‑completed dosing diaries.

The comparator is a matching placebo capsule containing 350 mg of Macrogol 6000 and no active substance. The placebo is identical in appearance, size, and packaging to the active drug and is administered orally using the same schedule (two capsules once daily). Compliance monitoring for the placebo follows the same procedures as for the active treatment, including capsule count and dosing diary review.

Efficacy will be evaluated by determining the proportion of participants who undergo a repeat prostate biopsy within 12 months of treatment initiation. This primary endpoint reflects the study’s objective to reduce the need for additional biopsies.

Secondary efficacy assessments, all performed at the 12‑month visit, include:

• Natural logarithm of prostate‑specific antigen (PIRADS) value measured by a centralized laboratory.
• PINS score, a validated symptom questionnaire.
• PIRADS score obtained from multiparametric MRI.
• Number of lesions identified on MRI.
• IS and IRANI scores, evaluated using their respective validated instruments.
• International Prostate Symptom Score (IPSS) and International Index of Erectile Function‑5 (IEF‑5) questionnaires.
• Proportion of participants diagnosed with prostate cancer within the 12‑month period.

Laboratory analyses for PSA will be conducted using standard immunoassays. MRI assessments will be performed according to a uniform protocol, and imaging will be centrally reviewed for PIRADS scoring. Patient‑reported outcomes (PINS, IPSS, IIEF‑5) will be collected via electronic case report forms. All data will be analyzed according to the predefined statistical analysis plan, comparing the Permixon® and placebo arms at the 12‑month time point.