Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium.

NCT03460704 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: Z7224L022016-004558-13
• Study Type: interventional
• Target: 287
• Locations: 12 countries
• Sites: 89

Brief Summary

The primary objective of the trial was to investigate the effect of the use of inhaled colistimethate sodium (CMS), administered twice a day (b.i.d.) via a specific nebulizer for 12 months, compared to placebo in subjects with non-cystic fibrosis bronchiectasis (NCFB) chronically infected with P. aeruginosa on the annualised frequency of pulmonary exacerbations.

Conditions

Non Cystic Fibrosis Bronchiectasis

Keywords

NCFB; NCFB pulmonary exacerbation; Bronchiectasis

Outcome Measures

Primary Outcomes (1)

• Mean Annual Non-cystic Fibrosis Bronchiectasis (NCFB) Pulmonary Exacerbation Rate

  The primary efficacy assessment for an individual subject was the frequency of pulmonary exacerbations (exacerbation rate). A pulmonary exacerbation was defined as the presence concurrently of at least three of the following eight symptoms/signs for at least 24 hours: * increased cough; * increased sputum volume and/or consistency; * increased sputum purulence; * new or increased haemoptysis; * increased wheezing; * increased dyspnoea; * increased fatigue/malaise and * episodes of fever (temperature ≥38°C). AND It was clinically determined that the subject required and was prescribed systemic antibiotic therapy. AND The episode of exacerbation lasted for at least 24 hours. The overall episode of exacerbation needs to last at least 24 hours, but individual symptoms/signs can last less than 24 hours (e.g, a temperature)

  12 months

Study Arms (2)

CMS (Colistimethate Sodium)

EXPERIMENTAL

Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials.

Drug: CMS

Placebo

PLACEBO COMPARATOR

Saline solution inhaled twice daily, provided and administered at the same way of the IMP.

Other: Placebo

Interventions

CMS DRUG

1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing). The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.

Also known as: Promixin

CMS (Colistimethate Sodium)

Placebo OTHER

1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.

Also known as: Saline Solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• are able and willing to give informed consent, following a detailed explanation of partecipation in the protocol and signed consent obtained;
• aged 18 years or older of either gender;
• diagnosed with NCFB by computerised tomography (CT) or high-resolution CT(HRCT) as recorded in the subject's notes and this is their predominant condition being treated;
• had at least 2 NCFB pulmonary exacerbations requiring oral or inhaled antibiotics or 1 NCFB pulmonary exacerbation requiring intravenous antibiotics in the 12 months preceding the Screening Visit (Visit 1) and had no pulmonary exacerbation with or without treatment during the period between Visit 1 and Visit 2;
• have a documented history of P. aeruginosa infection;
• are clinically stable and have not required a change in pulmonary treatment for at least 30 days before the Screening Visit (Visit 1);
• have pre-bronchodilator FEV1 ≥25% of predicted;
• had a positive sputum culture for P. aeruginosa from an adequate sample taken at the Screening Visit (Visit 1) or during the screening period.

You may not qualify if:

• known bronchiectasis as a consequence of cystic fibrosis (CF);
• known history of hypogammaglobulinaemia requiring treatment with immunoglobulin, unless fully replaced and considered immuno-competent by the Investigator;
• myasthenia gravis or porphyria;
• severe cardiovascular disease such as severe uncontrolled hypertension, ischaemic heart disease or cardiac arrhythmia and any other conditions that would confound the evaluation of safety, in the opinion of the Investigator;
• had major surgery in the 3 months prior to the Screening Visit (Visit 1) or planned inpatient major surgery during the study period;
• receiving treatment for allergic bronchopulmonary aspergillosis (ABPA);
• massive haemoptysis (greater than or equal to 300 mL or requiring blood transfusion) in the preceding 4 weeks before Screening Visit (Visit 1) or between Visit 1 and Visit 2;
• respiratory failure that would compromise patient safety or confound the evaluation of safety or efficacy of the study in the opinion of the Investigator;
• current active malignancy, except for basal cell carcinoma or squamous cell carcinoma of the skin without metastases;
• taking immunosuppressive medications (such as azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate, rituximab), and/or anti cytokine medications (such as anti-IL-6 and anti-tumour alpha necrosis factor products) in the preceding year before the Screening Visit (Visit 1);
• known history of human immunodeficiency virus (HIV);
• current treatment for non-tuberculous mycobacterial (NTM) lung disease or tuberculosis;
• known or suspected to be allergic or unable to tolerate colistimethate sodium (intravenous or inhaled) or other polymixins, including evidence of bronchial hyper-reactivity following inhaled colistimethate sodium;
• treatment with long term (≥ 30 days) prednisone at a dose of greater than 15 mg a day (or equivalent dose of any other corticosteroid) started within six months of the Screening Visit (Visit 1);
• new maintenance treatment with any oral macrolides ( (e.g. azithromycin/erythromycin/clarithromycin) within 30 days of the Screening Visit (Visit 1) or started between Visit 1 and Visit 2;

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (89)

Zambon Investigative Site

Newport Beach, California, 92663, United States

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Zambon Investigative Site

Palm Springs, California, 92262, United States

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Zambon Investigative Site

Reseda, California, 91324, United States

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Zambon investigative site

San Diego, California, 92103, United States

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Zambon Investgative Site

San Diego, California, 92120-5241, United States

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Zambon Investigative Site

Centennial, Colorado, 80112, United States

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Zambon Investigative Site

Jacksonville, Florida, 32204, United States

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Zambon Investigative Site

Kissimmee, Florida, 34741, United States

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Zambon Investigative Site

Orlando, Florida, 32803, United States

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Zambon investigative Site

St. Petersburg, Florida, 33704, United States

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Zambon Investigative Site

St. Petersburg, Florida, 33707, United States

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Zambon Investigative Site

Weston, Florida, 33331, United States

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Zambon Investigative Site

Chicago, Illinois, 60637, United States

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Zambon Investigative Site

Michigan City, Indiana, 46360, United States

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Zambon Investigative Site

Louisville, Kentucky, 40202, United States

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Zambon Investigative Site

Rochester, Minnesota, 55905, United States

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Zambon Investigative Site

Chesterfield, Missouri, 63017-3625, United States

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Zambon Investigative Site

Lebanon, New Hampshire, 03756-1000, United States

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Zambon Investigative Site

New York, New York, 10016, United States

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Zambon investigative site

Chapel Hill, North Carolina, 27514, United States

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Zambon Investigative Site

Durham, North Carolina, 27705, United States

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Zambon investigative site

Winston-Salem, North Carolina, 27265, United States

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Zambon Investigative Site

Portland, Oregon, 97239, United States

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Zambon Investigative Site

Tyler, Texas, 75708, United States

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ZambonInvestigative Site

Abingdon, Virginia, 24210, United States

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Zambon investigative site

Richmond, Virginia, 23219, United States

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Zambon Investigative Site

Northwest, Washington, 20007, United States

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Zambon Investigative Site

Buenos Aires, 1425, Argentina

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Zambon Investigative Site

Buenos Aires, 1426, Argentina

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Zambon Investigative Site

Buenos Aires, 1704, Argentina

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Zambon Investigative Site

Buenos Aires, 1842, Argentina

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Zambon Investigative Site

Buenos Aires, 1888, Argentina

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Zambon Investigative Site

Buenos Aires, B1602DQD, Argentina

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Zambon Investigative Site

Buenos Aires, B1900BNJ, Argentina

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Zambon investigative site

Buenos Aires, C1425AZB, Argentina

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Zambon Investigative Site

Quilmes, B1878FNR, Argentina

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Zambon Investigative Site

San Miguel de Tucumán, 4000, Argentina

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Zambon Investigative Site

Santa Fe, S3000ASF, Argentina

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Zambon Investigative Site

Adelaide, 5000, Australia

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Zambon investigative site

Concord, 2139, Australia

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Zambon investigative site

Greenslopes, 4120, Australia

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Zambon Investigative Site

Kent Town, 5067, Australia

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Zambon Investigative Site

South Brisbane, 4101, Australia

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Zambon investigative site

Spearwood, 6163, Australia

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Zambon investigative Site

Burlington, L7N 3V2, Canada

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Zambon investigative site

Kelowna, VIY 3H2, Canada

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Zambon Investigative Site

London, N6A 5W9, Canada

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Zambon Investigative Site

Montreal, H2X03E4, Canada

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Zambon Investigative Site

Ottawa, K1H8L6, Canada

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Zambon Investigative Site

Québec, G1V 4G5, Canada

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Zambon Investigative Site

Winnipeg, R2H 2A6, Canada

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Zambon Investigative Site

Amiens, 80054, France

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Zambon investigative site

Brest, 29200, France

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Zambon Investigative Site

Créteil, 94010, France

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Zambon investigative site

La Tronche, 38700, France

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Zambon investigative site

Lyon, 69004, France

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Zambon Investigative Site

Montpellier, 34295, France

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Zambon investigative site

Nice, 51069, France

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Zambon Investigative Site

Pessac, 33604, France

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Zambon investigative site

Reims, 51092, France

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Zambon Investigative Site

Toulouse, 31059, France

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Zambon Investigative Site

Frankfurt, 60596, Germany

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Zambon Investigative Site

Hanover, 30625, Germany

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Zambon Investigative Site

Athens, 11527, Greece

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Zambon Investigative Site

Haifa, 34362, Israel

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Zambon Investigative Site

Jerusalem, 9703102, Israel

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Zambon Investigative Site

Kfar Saba, 4428164, Israel

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Zambon Investigative Site

Milan, 20122, Italy

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Zambon Investigative Site

Monza, 20900, Italy

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Zambon Investigative Site

Christchurch, 8011, New Zealand

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Zambon Investigative Site

Havelock North, 4130, New Zealand

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Zambon Investigative Site

Mount Cook, 6021, New Zealand

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Zambon Investigative Site

Tauranga, 3110, New Zealand

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Zambon Investigative Site

Bialystok, 15-044, Poland

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Zambon Investigative Site

Bielsko-Biala, 43-300, Poland

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Zambon Investigative Site

Grudziądz, 86300, Poland

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Zambon Investigative Site

Krakow, 31-066, Poland

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Zambon Investigative Site

Legnica, 59220, Poland

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Zambon Investigative Site

Lodz, 94-048, Poland

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Zambon Investigative Site

Lublin, 20-089, Poland

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Zambon Investigative Site

Ostrowiec Świętokrzyski, 27-400, Poland

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Zambon Investigative Site

Piaseczno, 05-500, Poland

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Zambon Investigative Site

Proszowice, 32-100, Poland

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Zambon Investigative Site

Rzeszów, 35-205, Poland

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Zambon Investigative Site

Sosnowiec, 41-200, Poland

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Zambon Investigative Site

Warsaw, 01-456, Poland

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Zambon Investigative Site

Wroclaw, 51-162, Poland

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Zambon Investigative Site

Guimarães, 4835-044, Portugal

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Zambon Investigative Site

Lisbon, 1649035, Portugal

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MeSH Terms

Conditions

Bronchiectasis

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Michela Meroni - Clinical Trial Manager
• Organization: Zambon S.p.A.

clinicaltrials@zambongroup.com

+39 02 665241

Study Officials

• Paola Castellani, MD

  Zambon S.p.A.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: March 9, 2018
• Study Start: January 29, 2018
• Primary Completion: March 15, 2022
• Study Completion: March 15, 2022
• Last Updated: December 29, 2023
• Results First Posted: December 29, 2023

Record last verified: 2023-12

Locations

DE (2); US (27); IT (2); PT (2); AR (11); NZ (4); FR (10); IL (3); CA (7); AU (6); PL (14); GR (1)