Changwon, Korea, Republic of

Clinical Trial of the Efficacy and Safety of Raphamin in Prevention of Recurrences of Chronic Bacterial Cystitis

Trial design: double blind, placebo-controlled, randomized in parallel groups clinical trial. The trial includes female outpatients aged 18 years or older with typical symptoms of chronic bacterial cystitis. The severity of typical symptoms of recurrence (exacerbation) should be 7 points or more according to the subscale "Typical symptoms" of the scale "Acute Cystitis Symptom Scale" (ACSS). At Visit 1 (Day 1), after signing the patient information sheet and the informed consent form for participation in the clinical trial, complaints and medical history are collected, a physical examination is performed, and the severity of typical symptoms of cystitis is assessed using ACSS, collection of urine biosamples for urine analysis with microscopy and bacteriological examination (for identification the sensitivity of microorganisms to antibiotics), ultrasound examination of the urinary system (kidneys, bladder), and concomitant therapy is recorded. Urinalysis, general and biochemical blood tests are planned in at least 190 patients. If the patient meets inclusion criteria and does not meets exclusion inclusion criteria at Visit 1 (Day 1), the patient is randomized to one of two groups: patients of Group 1 take Phosphomycin (3 g once) and Raphamin according to the therapeutic and preventive regimen for 10 days; patients of Group 2 use Phosphomycin (3 g once) and Placebo according to the Raphamin regimen for 10 days. If there is no effect from treatment within 48 hours or phosphomycin-resistant strains are detected, the physician conducts unscheduled visit and gives the patient an alternative drug Cefixime (400 mg). Cefixime is taken 1 times a day at a dose of 400 mg for 5 days or more (the duration of the course is determined by the physician). All patients are provided with Phosphomycin, if resistance to it is detected - with alternative antibiotic Cefixime. If microorganisms resistant to both Phosphomycin and Cefixime are detected, the patient is excluded from the trial, and the physician prescribes a treatment strategy in accordance with current standards. In Electronic Patient Diary (EPD) the patient records the severity of typical cystitis symptoms using ACSS once a day at approximately the same time. Symptoms are recorded in the EPD from the patient's enrollment until Visit 2 (within 10 days of study drug administration), as well as during 10 days of treatment for each subsequent relapse (exacerbation). In addition, any possible deterioration of the patient's condition (if applicable) is recorded in EDP to assess safety and record adverse events. The study physician instructs patients to complete the diary. The first ACSS marks in the EDP are made by patient together with physician at Visit 1. EDP is available for filling throughout the patient's participation in the study. Once a week, the patients get SMS reminder: "If you have symptoms of the disease, enter them in the diary and contact the study physician. Don't forget to take your medication." In total, patient's follow-up lasts for 24 weeks. In the process of treatment and observation, 4 visits are scheduled: at day 1 (Visit 1) and day 11 (Visit 2), then at weeks 12 and 24 (Visits 3, 4). Visits 1, 2 and 4 are face-to-face (patient visits trial site); physician conducts physical examination, records symptoms and concomitant therapy, and checks the EPD. At Visit 2 (Day 11+3), the physician gives Phosphomycin/Cefixime and a study drug to patient, to treat a possible subsequent recurrence of cystitis. Blood and urine biosamples are taken from the patient who signed the ICF for taking biological samples (for safety assessment). The study drug received by the patient at Visit 1 should be returned to assess the patient's adherence to the study treatment. Phosphomycin/Cefixime also returns. Visit 3 (Week 12 ± 3 days) is conducted by correspondence (telephone), in order to interview the patient about her condition. In case of new recurrence of cystitis, patient contacts with trial physician by phone. On the basis of complaints and symptoms, physician makes conclusion about the onset of chronic cystitis recurrence. Patient completes ACSS in EPD. For a recurrence of cystitis, patient takes Phosphomycin (or Cefixime) and trial product (Raphamin/Placebo for 10 days). At the end of 10 days of treatment, an unscheduled face-to-face visit takes place (Day 11+3 days after the onset of recurrence), at which the patient returns the trial product and Phosphomycin/Cefixime, then the physician dispenses a new pack of trial product and Phosphomycin (or Cefixime) to treat a possible new recurrence of cystitis. Visit 4 (Week 24 ± 3 days) is the final one; complaints are assessed, the patient undergoes a physical examination, returns the trial product and fills in a visual analogue scale (VAS), which assesses the degree of patient satisfaction with the therapy.

A 52-week, Placebo- and Active- Controlled (Roflumilast, Daliresp® 500µg) Study to Evaluate the Efficacy and Safety of Two Doses of CHF6001 DPI (Tanimilast) as add-on to Maintenance Triple Therapy in Subjects With COPD and Chronic Bronchitis. (PILLAR)

Safety and Efficacy Study of Ftortiazinon in the Treatment of Patients With Complicated Urinary Tract Infections Caused by P. Aeruginosa

The study is divided into 2 phases. The course of treatment will be single (course of therapy with the drug/placebo under study) for a group consisting of three cohorts, and also single for a group of phase 2 participants (770 patients in total) consisting of two cohorts groups. The recruitment of patients to the second phase will commence after the evaluation of the data on safety and efficiency by the expert commission within the framework of reviewing the amendment to the current Study Protocol. At the second phase, it is proposed to study the optimal dosage chosen based on the results of the first (search phase) study. This study is aimed at evaluating the efficacy, safety and tolerability of the drug Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA), in comparison with placebo in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA), in the treatment of patients with complicated urinary tract infections (complicated UTIs) caused by P. aeruginosa. FIRST PHASE (search phase) At this phase, the patients will take the drug Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). According to the results of the screening of patients who have signed the Informed Consent Form, the patients are recruited in three groups with different doses of the drug. The total number of patients who received the drug or placebo will be at least 240 people according to the following scheme: Group 1 (80 patients) - Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) plus placebo. The drug is administered according to the following scheme on the first day: the first administration of Ftortiazinon 300 mg (1 tablet) plus placebo (1 tablet) 30 minutes after eating with lukewarm water, the second administration - 1 tablet (300 mg) after 12 hours, then within 6 days the drug is prescribed 1 tablet once a day plus 1 tablet of placebo (interval: 12 hours) 30 minutes after eating. Group 2 (80 patients) - Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation). The drug is administered according to the following scheme on the first day: the first administration of 600 mg (2 tablets) 30 minutes after eating with lukewarm water, the second administration - 1 tablet (300 mg) after 12 hours, then within 6 days the drug is prescribed 1 tablet twice a day at intervals of 12 hours. Group 3 (80 patients) - placebo in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). The drug is administered according to the following scheme on the first day: the first administration of 2 tablets 30 minutes after eating with lukewarm water, the second administration - 1 tablet after 12 hours, then within 6 days the drug is prescribed 1 tablet twice a day at intervals of 12 hours 30 minutes after eating. For all groups: Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). The drug is administered according to the following scheme: the drug with a dosage of 1.0 g is dissolved in 2.4 ml of sterile water for injection or 0.9% sodium chloride solution, or 0.5-1% lidocaine hydrochloride solution; then injected deep into the muscle, into the upper outer quadrant of the buttocks after pre-aspiration every 12 hours for 7 days*. SECOND PHASE (confirmation phase) The transition to this phase of the study to assess efficacy and safety of the drug Ftortiazinon will be carried out after selecting the optimal dosage according to the results of the first (confirmation phase) study. This transition will be carried out by making a corresponding amendment to the Study Protocol with the provision of data confirming the efficacy and safety of the selected therapeutic scheme. The assessment will be conducted according to the results of the 21-day surveillance for patients after completion of therapy with a drug/placebo. Group 1 patients will take the drug Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA) in accordance with the dosage regimen selected at the first phase. Maxipime® is a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). It is administered according to the following scheme: the drug with a dosage of 1.0 g is dissolved in 2.4 ml of sterile water for injection or 0.9% sodium chloride solution, or 0.5-1% lidocaine hydrochloride solution; then injected deep into the muscle, into the upper outer quadrant of the buttocks after pre-aspiration every 12 hours for 7 days. Group 2 patients will take placebo in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). Placebo is taken according to the scheme corresponding to those chosen at the first phase. Maxipime® is a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). It is administered according to the following scheme: the drug with a dosage of 1.0 g is dissolved in 2.4 ml of sterile water for injection or 0.9% sodium chloride solution, or 0.5-1% lidocaine hydrochloride solution; then injected deep into the muscle, into the upper outer quadrant of the buttocks after pre-aspiration every 12 hours for 7 days. Administration/injection of drugs Ftortiazinon/placebo and Maxipime® should be carried out simultaneously, preferably in one and the same time every day. Let the administration of Ftortiazinon/placebo will be for 30 min after administration of the drug Maxipime®. The duration of therapy with Maxipime® will be 7 calendar days; however, if the patient has no positive dynamics in the evaluation of clinical symptoms of complicated UTIs, there is an increase in uropathogen in the urine culture obtained on Visit 2, and the duration of therapy can be increased to a total of 14 calendar days.