Clinical trial NCT03551210: Efficacy and Safety of Nemonoxacin vs Levofloxacin in Adult Patients With Community-Acquired Pneumonia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Bacterial
Keywords: nemonoxacin
community-acquired pneumonia
quinolones
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
Collaborators: name: OCT Clinical Trials
First posted: 2018-06-11
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All eligible patients will be randomized to receive either treatment with Nemonoxacin or Tavanic® in a ratio of 1:1.
Primary purpose: TREATMENT

Brief 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).

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With Clinical Success as Judged by the Investigator
timeFrame: Visit 4 (within 7-9 days after last dose)
Secondary outcomes:
measure: Number of Patients With Clinical Success as Judged by the Investigator
timeFrame: Visit 2(day 4/8 ot treatment), Visit 3 (within 1-2 days after last dose)
measure: Number of Patients With Infection Relapse
timeFrame: Visit 5 (within 21-23 days after last dose)
measure: Time to Switch Therapy From Intravenous to Oral Therapy
timeFrame: Up to Visit 2 (day 4/8 ot treatment)
measure: Number of Patients Required for Other Antibiotic Treatment
timeFrame: Up to 21-23 days after last dose
measure: Number of Patients With Microbiological Success
timeFrame: Visit 2 (day 4/8 ot treatment), 3 (within 1-2 days after last dose), 4 (within 7-9 days after last dose)
Other outcomes:
measure: Nemnoxacin Concentration Changes
timeFrame: 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
measure: Area Under the Concentration-time Curve (AUC) of Nemonoxacin
timeFrame: 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
measure: Сlearance (CL) of Nemonoxacin
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of Nemonoxacin
timeFrame: 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
measure: Terminal Elimination Half-life (T1/2) of Nemonoxacin
timeFrame: 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
Locations:
city: Ekaterinburg
country: Russian Federation
facility: Central city hospital #7
city: Ekaterinburg
country: Russian Federation
facility: City clinical hospital #40
city: Ivanovo
country: Russian Federation
facility: Regional budget healthcare institution "Ivanovo regional clinical hospital"
city: Moscow
country: Russian Federation
facility: City clinical hospital #1 n.a. N.I. Pirogov of Moscow Healthcare Department
city: Moscow
country: Russian Federation
facility: City Clinical hospital n.a. V. V. Vinogradov
city: Moscow
country: Russian Federation
facility: FSOE Main Military Clinical Hospital n.a. academician N.N. Burdenko of the Ministry of Defence of the Russian Federation
city: Moscow
country: Russian Federation
facility: SBHI Moscow City clinical hospital # 15 n.a. O.M. Filatov of Moscow Healthcare Department
city: Novosibirsk
country: Russian Federation
facility: City Clinical Hospital #25
city: Novosibirsk
country: Russian Federation
facility: City clinical hospital #2
city: Novosibirsk
country: Russian Federation
facility: SBHI of Novosibirsk region City Clinical Hospital of Emergency Medical Care №2
city: Petrozavodsk
country: Russian Federation
facility: Republic Hospital named after V.A. Baranov
city: Pskov
country: Russian Federation
facility: Pskov regional clinical hospital
city: Saint Petersburg
country: Russian Federation
facility: Baltic Medicine LLC
city: Saint Petersburg
country: Russian Federation
facility: City Hospital #15
city: Saint Petersburg
country: Russian Federation
facility: City Hospital #26
city: Saint Petersburg
country: Russian Federation
facility: City hospital #38 n.a. N.A. Semashko
city: Saint Petersburg
country: Russian Federation
facility: Mariinsky City Hospital
city: Saint Petersburg
country: Russian Federation
facility: Multidisciplinary City Hospital # 2
city: Saint Petersburg
country: Russian Federation
facility: Scientific Research Institute of Influenza of the Ministry of Healthcare of Russian Federation
city: Saratov
country: Russian Federation
facility: Regional clinical hospital
city: Smolensk
country: Russian Federation
facility: Clinical hospital of emergency medical care
city: Smolensk
country: Russian Federation
facility: Scientific Research Institute of Antimicrobial Therapy of Smolensk State Medical University
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University of the Ministry of Healthcare of Russian Federation
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Hospital #1
Study officials:
affiliation: R-Pharm
name: Mikhail Samsonov
role: STUDY_DIRECTOR
References: