A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections with Pseudomonas aeruginosa in Subjects with Non-Cystic Fibrosis Bronchiectasis, including 28 Day Open-Label Extension (ORBIT-4)

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-006-15
• Date of registration: 28/05/2015
• Prospective Registration: No
• Primary sponsor: Aradigm Corporation,
• Public title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections with Pseudomonas aeruginosa in Subjects with Non-Cystic Fibrosis Bronchiectasis, including 28 Day Open-Label Extension (ORBIT-4)
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections with Pseudomonas aeruginosa in Subjects with Non-Cystic Fibrosis Bronchiectasis, including 28 Day Open-Label Extension (ORBIT-4)
• Date of first enrolment: 15/04/2015
• Target sample size: 15
• Recruitment status: Complete
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=006-15
• Study type: Interventional
• Study design: This is a multinational, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of Pulmaquin compared to placebo in the management of chronic lung infections with P. aeruginosa in subjects with non-CF bronchiectasis with a history of pulmonary exacerbations. A sufficient number of subjects across approximately 80 study sites will be enrolled to ensure 255 subjects are randomized in a 2:1 ratio to Pulmaquin (170 subjects) and placebo (85 subjects).; This study will consist of an up to 42-day Screening Phase, a Double-Blind Phase including six 56-day treatment cycles, and a 28-day Open-Label Extension. Each enrolled subject will remain on their prescribed standard medications and therapeutic treatment regimen for the duration of the study to which study drug will be added. For exceptions, please see inclusion/exclusion criteria. Each treatment cycle will consist of 28 days of study drug treatment (On-treatment Period) fol
• Phase: III

Countries of recruitment

Andorra, Colombia, Hungary, Ireland, Israel, Italy, Mexico, Peru, Spain, United Kindgdom, United States

Contacts

• Name: Aracely Astahuaman Galvez Durand
• Affiliation: INTRIALS-PERU INVESTIGACIONES CLINICAS S.R.L.

• Name: Aracely Astahuaman Galvez Durand
• Affiliation: INTRIALS-PERU INVESTIGACIONES CLINICAS S.R.L.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Are willing and able to provide written informed consent.
2. Are males or females who are 18 year of age or older and are able to walk.
3. Have had a confirmed diagnosis of non-CF bronchiectasis per computerized tomography (or high resolution computerized tomography) showing bronchial wall dilatation (internal bronchial lumen diameter greater than accompanying pulmonary artery or lack of tapering) with or without bronchial wall thickening.
4. Have a documented history of at least 2 pulmonary exacerbations treated with courses of antibiotics within the last 12 months.
5. Have forced expiratory volume in 1 second (FEV1) ≥ 25% of predicted values at the Screening Visit (Visit 0).
6. Have positive documented P. aeruginosa in a sputum/deep-throat swab culture (or bronchoalveolar lavage [BAL] or bronchoscopic specimen) prior to the Screening Visit (Visit 0). Subjects without documented P. aeruginosa prior to Screening who meet all other eligibility criteria must have at least two sputum samples or deep-throat swabs collected 3-4 or more weeks apart from each other during the 42-day Screening Phase. Two of the samples collected must test positive for P. aeruginosa. These two positive tests must be from samples taken a minimum of 3-4 or more weeks apart.
7. Have positive P. aeruginosa in the sputum/deep-throat swab culture collected at the Screening Visit (Visit 0) and at least one P. aeruginosa isolate non-resistant to ciprofloxacin. If the sputum sample is negative for P. aeruginosa, or only shows resistant P. aeruginosa isolates, the sputum/swab culture can be repeated multiple times during Screening to document the presence of P. aeruginosa. In subjects without documented P. aeruginosa prior to Screening who meet all other eligibility criteria and who had two or more sputum cultures or deep-throat swab cultures obtained 3-4 or more weeks apart from each other during Screening, at least one P. aeruginosa isolate taken after 3-4 or more weeks must be non-resistant to ciprofloxacin for the subject to be considered eligible for randomization. The qualifying sputum culture results must be available within the 42-day Screening Phase.

Exclusion criteria:
1. Presentar una exacerbacion pulmonar durante la Fase de Seleccion (entre la firma del ICF y la aleatorizacion), definida como la necesidad de tratamiento agudo con antibioticos inhalados, orales o intravenosos.
2. Presentar diagnostico clinico de FQ.
3. Presentar diagnostico primario de Enfermedad Pulmonar Obstructiva Cronica (EPOC) relacionada con un historial de tabaquismo de mas de 10 paquetes año.
4. Presentar diagnostico actual de aspergilosis broncopulmonar alergica activa.
5. Haber recibido cualquier antibiotico antipseudomona intravenoso, oral o inhalado (excepto los macrolidos cronicos eritromicina, claritromicina o azitromicina con dosis estable) dentro de 28 dias antes de la Visita 1.
6. Tener alergia a ciprofloxacino, gemifloxacino, levofloxacino, moxifloxacino o norfloxacino.
7. Tener alergia conocida a productos de soja.
8. Haber utilizado tizanidina dentro de 28 dias antes de la Visita 1 y que necesitaria utilizar tizanidina durante el estudio (porque la tizanidina esta contraindicada debido a una interaccion PK con ciprofloxacino).
9. Haber iniciado oxigeno suplementario dentro de 28 dias antes de la Visita 1.
10. Haber utilizado cualquier corticosteroide intravenoso o intramuscular o haber utilizado corticosteroide oral > 10 mg/dia o > 20 mg en dias alternos (equivalentes de prednisona o prednisolona) dentro de 28 dias de la Visita 1.
3. Have primary diagnosis of Chronic Obstructive Pulmonary Disease (COPD) related to smoking history of greater than 10 pack years.
4. Have a current diagnosis of active allergic bronchopulmonary aspergillosis.
5. Have received any intravenous, oral, or inhaled anti-pseudomonal antibiotic (except chronic macrolides erythromycin, clarithromycin or azithromycin with a stable dose) within 28 days prior to Visit 1.
6. Have an allergy to ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, or norfloxacin.
7. Have a known allergy to soy products.
8. Have used tizanidine within 28 days prior to Visit 1 and would need to use tizanidine during the study (because tizanidine is contraindicated due to a PK interaction with ciprofloxacin).
9. Have initiated supplemental oxygen within 28 days prior to Visit 1.


Age minimum: 18
Age maximum: 100
Gender: --

Health Condition(s) or Problem(s) studied

Bronchiectasis

J47

-J47 Bronchiectasis
Bronchiectasis

Intervention(s)

Post-Screening, subjects will be randomized to Pulmaquin or inhaled placebo. The study drug will be administered by inhalation once daily (6 mL total) during six 28-day On-treatment Periods. Subjects will self-administer study drug at home every day except for Visits 1, 2, 4, 6, 8, 10, 12, and 14 when they will self-administer study drug at the study site.
Active: Pulmaquin
• Pulmaquin, which consists of the following:
o Ciprofloxacin for Inhalation (CFI, 50 mg/mL), 150 mg in 3 mL
o Free Ciprofloxacin for Inhalation (FCI, 20 mg/mL), 60 mg in 3 mL
Placebo: Placebo Liposomes for Inhalation (PLI)
• Placebo, which consists of the following:
o Control Liposomes for Inhalation (CLI, 5 mg/mL), 15 mg total lipid in 3 mL
o Normal saline (0.9%) 3 mL
All subjects will receive once daily Pulmaquin during the Open-Label Extension.

Source(s) of Monetary Support

Industria Farmaceutica

Ethics review

Status: Approved
Approval date: 13/01/2015
Contact:

[e-mail]

Via Libre

4331396

[e-mail]

Status: Approved
Approval date: 12/02/2015
Contact:

[e-mail]

Comite Institucional de Etica en Investigacion de la Asociacion Benefica Prisma

616-5500 Anx. 246

[e-mail]

Status: Approved
Approval date: 17/02/2015
Contact:

[e-mail]

Via Libre

4331396

[e-mail]

Status: Approved
Approval date: 06/05/2015
Contact:

[e-mail]

Hospital Nacional Guillermo Almenara Irigoyen - EsSalud

999436950

[e-mail]

Status: Approved
Approval date: 05/07/2016
Contact:

[e-mail]

Via Libre

4331396

[e-mail]