This multicenter, randomized, double-blind study is a phase III evaluates the safety and effectiveness of CLR prolonged-release tablets in patients with chronic venous insufficiency, has been shown to be effective in reducing the symptoms of itching, edema, spontaneous pain, and night cramps chronic venous disease.

Inclusion Criteria:

• Participants with an age ≥ 18 and ≤ 80 years
• Diagnosed primary venous disease of the lower limbs in stage C2 - C5 according to the CEAP classification, involvement of the venous system of the lower limbs is verified by duplex ultrasonography
• Presence of objective signs and subjective symptoms of the disease (classified according to rVCSS score ≥ 4)
• Participants not using or planning to use compression therapy by their own decision
• Provision of written informed consent as approved by the Ethics Committee (EC).

Exclusion Criteria:

• Use of a venoactive drug in the last month

• Regular use of compression therapy or use of mechanical devices for reduction of edema in the last month

• Heart Failure (NYHA class III and IV), congestive heart failure with peripheral edema

• eGFR < 30 mL/min/1.73 m² at screening or chronic kidney disease documented in the medical history

• ALT or AST more than 3 times the upper limit of normal range at screening or advanced liver disease documented in the medical history

• Deep venous thrombosis lower limb thrombosis and / or documented residual venous obstruction or deep venous reflux due to post-thrombotic alterations in the deep venous system

• Superficial venous thrombosis of the lower limbs in the previous 6 months

• Congenital venous/lymphatic malformation

• Neuropathy of any aetiology

• Diabetic foot syndrome

• Refractory (uncontrollable) hypertension (inability to therapeutically achieve a systolic blood pressure ≤ 160 mmHg or a diastolic blood pressure ≤ 100 mmHg)

• Symptomatic ischemic disease of lower limbs

• Lymphoedema: primary, posttraumatic, postoperative, post-radiation, malignant

• Manual/instrumental lymphatic drainage in the last 3 months

• Invasive procedure on the lower limbs in the last 6 months

• Trauma of the lower extremity that has not fully healed

• Use of oral/parenteral anticoagulants

• Use of dual antiplatelet therapy

• Use of loop diuretics

• Use of oestrogens or progesterone and its derivates

  -. Use of oral/parental corticosteroids in the last 6 weeks

• Chronic pain treatment ≥ 14 days

• Use of psychopharmaceuticals affecting fluid retention (antipsychotics, combined antidepressants)

• Severe obesity (BMI > 40 kg/m2)

• Participants with active malignant disease or malignant disease in remission for less than 5 years

• Myeloproliferative or immune disorders

• Contraindications to the IMP/Placebo administration

• Hypersensitivity to the IMP/Placebo excipients. General Conditions

• Pregnant or breastfeeding women

• Women of child-bearing potential not using at least one effective contraceptive method for the entire trial

• Participation in other investigational drug or device clinical trials within 30 days prior to study screening

  -. Participants legally or mentally incapacitated unable to give informed consent for the participation in this trial

• Participants unable or unwilling to comply with appointments or all protocol requirements.