Efficacy and Safety of Nemonoxacin vs Levofloxacin in Adult Patients With Community-Acquired Pneumonia

Pneumonia, Bacterial Clinical Trial

Official title:

An International, Multicenter, Randomized, Double-blind, Double-dummy, Two-way, Parallel Group, Controlled Study to Compare the Efficacy and Safety of Intravenous and Oral Nemonoxacin Versus Tavanic® in Adult Patients With Community-acquired Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03551210
• Other study ID #: CJ01060044
• Status: Completed
• Phase: Phase 3
• Start date: May 4, 2016
• Est. completion date: December 26, 2017

Study information

• Verified date: January 2023
• Source: R-Pharm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to evaluate the clinical efficacy of treatment with Nemonoxacin compared with Tavanic® in patients with community-acquired pneumonia (CAP).

Description:

Treatment-naive patients with CAP and patients with treatment failure were screened and if met the eligible criteria were randomized to receive either treatment with investigational product or comparator. Patients started to receive intravenous therapy with Nemonoxacin or Tavanic® and then upon a decision of investigator patients were switched to oral therapy with the same product.

Intravenous therapy included two consequence infusions (antibiotic solution and placebo solution) to maintain blinding. Intravenous therapy should have been given for at least 3 days and could have been prolonged by a decision of investigator up to 7 days. Then investigator switched a patient from intravenous to oral therapy on Day 4(8) of the study if the specific criteria of clinical stability were achieved. To maintain blinding during oral antibiotic therapy each Tavanic® tablet was placed into a capsule shell (over-encapsulated), that was identical in appearance to a Nemonoxacin-containing capsules.

The average duration of treatment (including intravenous and oral therapy) for each patient was 7(14) days and during this period patients should have stayed at hospital. After completion of the treatment patients could have been discharged from the hospital and returned for examinations within 1-2 days after the last dose (end of treatment visit). Then the patients attended the investigational site within 7-9 days after the last dose (test of cure visit). Then the investigator contacted the patients by phone within 21-23 days after the last dose (long-term follow-up visit).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 342
• Est. completion date: December 26, 2017
• Est. primary completion date: December 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Written informed consent obtained from the patient.

• Patients with moderate to severe community-acquired pneumonia who need inpatient treatment but do not need intensive care unit treatment.

• The presence of at least 3 of the following symptoms / signs:

1. cough;

2. purulent sputum production;

3. tachypnea (respiratory rate > 24 breathes/minute);

4. chills;

5. fever (rectal / tympanic temperature = 38.5°C or axillary / oral / skin temperature = 38.5°C);

6. white blood cells (WBC) count of = 10.0 x 10^9/L or = 15% immature neutrophils (bands; regardless of peripheral WBC count).

• Radiological evidence of (a) new infiltrate(s) consistent with bacterial pneumonia at baseline.

• Treatment-naive patients or patients who have received single dose of a short-acting antibacterial drug within 24 hours of enrollment or patients with treatment failure who have received antibiotics (with the exception of quinolones or fluoroquinolones) for less than 72 hours.

• Consent to use contraception during participation in the study (for women of childbearing potential and men).

Exclusion Criteria:

• Known hypersensitivity to quinolones, fluoroquinolones or any of the excipients.

• Female patients who are pregnant or nursing.

• History of tendon disease / disorder related to quinolone treatment.

• Known congenital or documented-acquired QT / QTc(F) prolongation on ECG (QTc(F) interval more than 450 ms); concomitant use of drugs, reported to increase the QT interval; uncorrected hypokalaemia and uncorrected hypomagnesemia; clinically relevant bradycardia; clinically relevant heart failure with reduced left-ventricular ejection fraction; previous history of symptomatic arrhythmias.

• History of bronchiectasis, cystic fibrosis, bronchial obstructions excluding chronic obstructive pulmonary disease.

• History of epilepsy and/or history of psychotic disorder.

• Patients with history of myasthenia gravis.

• Patients with diabetes mellitus.

• Known glucose-6-phosphate dehydrogenase deficiency.

• Active hepatitis or decompensated cirrhosis.

• Alanine transaminase or aspartate transaminase increase > 3 fold upper limit of normal (ULN).

• Patients with creatinine = 1.1 fold ULN.

• Patients requiring concomitant systemic or inhaled antibiotics (e.g., tobramycin).

• Known or suspected active tuberculosis or endemic fungal infection.

• Concomitant immunosuppressive therapy including a long-term (more than 2 weeks) treatment with oral or intravenous glucocorticoids at doses of 20 mg and higher of prednisone daily or an equivalent dose of other glucocorticoids.

• Patients known to have HIV-positive status or AIDS or known to have other disease that seriously affects the immune system such as active haematological or solid organ malignancy, or splenectomy.

• History of drug or alcohol abuse.

• Patients have received quinolones or fluoroquinolones within 14 days before enrollment.

• Previous enrolment in this study or participation in another study within the previous 4 weeks.

• Patients with any severe medical condition as determined by medical history that, in the opinion of the investigator, does not allow the patient to carry out all planned procedure of the protocol.

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Bacterial

Intervention

Drug:
• Nemonoxacin
Solution for infusion, 500 mg (250 ml)
• Nemonoxacin
Capsules, 250 mg
• Tavanic
Solution for infusion, 500 mg (100 ml)
• Tavanic
Film coated tablets (each tablet is placed into a capsule shell (overencapsulated) for blinding purposes), 250 mg
• Placebo (250 ml)
0.9% NaCl (250 ml), solution for infusion
• Placebo (100 ml)
0.9% NaCl (100 ml), solution for infusion

Locations

Country	Name	City	State
Russian Federation	Central city hospital #7	Ekaterinburg
Russian Federation	City clinical hospital #40	Ekaterinburg
Russian Federation	Regional budget healthcare institution "Ivanovo regional clinical hospital"	Ivanovo
Russian Federation	City clinical hospital #1 n.a. N.I. Pirogov of Moscow Healthcare Department	Moscow
Russian Federation	City Clinical hospital n.a. V. V. Vinogradov	Moscow
Russian Federation	FSOE Main Military Clinical Hospital n.a. academician N.N. Burdenko of the Ministry of Defence of the Russian Federation	Moscow
Russian Federation	SBHI Moscow City clinical hospital # 15 n.a. O.M. Filatov of Moscow Healthcare Department	Moscow
Russian Federation	City clinical hospital #2	Novosibirsk
Russian Federation	City Clinical Hospital #25	Novosibirsk
Russian Federation	SBHI of Novosibirsk region City Clinical Hospital of Emergency Medical Care ?2	Novosibirsk
Russian Federation	Republic Hospital named after V.A. Baranov	Petrozavodsk
Russian Federation	Pskov regional clinical hospital	Pskov
Russian Federation	Baltic Medicine LLC	Saint Petersburg
Russian Federation	City Hospital #15	Saint Petersburg
Russian Federation	City Hospital #26	Saint Petersburg
Russian Federation	City hospital #38 n.a. N.A. Semashko	Saint Petersburg
Russian Federation	Mariinsky City Hospital	Saint Petersburg
Russian Federation	Multidisciplinary City Hospital # 2	Saint Petersburg
Russian Federation	Scientific Research Institute of Influenza of the Ministry of Healthcare of Russian Federation	Saint Petersburg
Russian Federation	Regional clinical hospital	Saratov
Russian Federation	Clinical hospital of emergency medical care	Smolensk
Russian Federation	Scientific Research Institute of Antimicrobial Therapy of Smolensk State Medical University	Smolensk
Russian Federation	Siberian State Medical University of the Ministry of Healthcare of Russian Federation	Tomsk
Russian Federation	Ulyanovsk Regional Clinical Hospital	Ulyanovsk
Russian Federation	Voronezh Regional Clinical Hospital #1	Voronezh

Sponsors (2)

Lead Sponsor	Collaborator
R-Pharm	OCT Clinical Trials

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Nemnoxacin Concentration Changes	Cmax - The peak Nemonoxacin concentration at Day 1-2 of treatment; C-22.5hours - 22.5-h drug concentration of Nemonoxacin	Day 1 pre-dose and 0, 0.5, 2.5, 4, 6, 12, 16 and 22.5 (= Day 2 pre-dose) hrs after the end of first infusion on Day 1 of treatment
Other	Area Under the Concentration-time Curve (AUC) of Nemonoxacin	AUC (0-22.5) - Area under the concentration-time curve from 0 to 22.5 hours of Nemonoxacin; AUC(0-8) - Areas under the concentration-time curve from 0 h to infinity of Nemonoxacin	Day 1 pre-dose and 0, 0.5, 2.5, 4, 6, 12, 16 and 22.5 (= Day 2 pre-dose) hrs after the end of first infusion on Day 1 of treatment
Other	?learance (CL) of Nemonoxacin	Total systemic clearance of Nemonoxacin	Day 1 pre-dose and 0, 0.5, 2.5, 4, 6, 12, 16 and 22.5 (= Day 2 pre-dose) hrs after the end of first infusion on Day 1 of treatment
Other	Volume of Distribution at Steady State (Vss) of Nemonoxacin	Volume of distribution at steady state of Nemonoxacin	Day 1 pre-dose and 0, 0.5, 2.5, 4, 6, 12, 16 and 22.5 (= Day 2 pre-dose) hrs after the end of first infusion on Day 1 of treatment
Other	Terminal Elimination Half-life (T1/2) of Nemonoxacin	Terminal elimination half-life of Nemonoxacin	Day 1 pre-dose and 0, 0.5, 2.5, 4, 6, 12, 16 and 22.5 (= Day 2 pre-dose) hrs after the end of first infusion on Day 1 of treatment
Primary	Number of Patients With Clinical Success as Judged by the Investigator	Clinical response is evaluated as clinical success if: all signs and symptoms of pneumonia are resolved or improved with no worsening or appearance of new signs and symptoms of pneumonia; there is no requirement for additional antibiotic therapy; chest roentgenograms (CT scans) are cured or improved	Visit 4 (within 7-9 days after last dose)
Secondary	Number of Patients With Clinical Success as Judged by the Investigator	Clinical response is evaluated as clinical success if: all signs and symptoms of pneumonia are resolved or improved with no worsening or appearance of new signs and symptoms of pneumonia; there is no requirement for additional antibiotic therapy	Visit 2(day 4/8 ot treatment), Visit 3 (within 1-2 days after last dose)
Secondary	Number of Patients With Infection Relapse		Visit 5 (within 21-23 days after last dose)
Secondary	Time to Switch Therapy From Intravenous to Oral Therapy		Up to Visit 2 (day 4/8 ot treatment)
Secondary	Number of Patients Required for Other Antibiotic Treatment		Up to 21-23 days after last dose
Secondary	Number of Patients With Microbiological Success	Microbiological response is evaluated as microbiological success if culture study demonstrates eradication of pathogen or no material available for culture because of clinical success	Visit 2 (day 4/8 ot treatment), 3 (within 1-2 days after last dose), 4 (within 7-9 days after last dose)