A 24-wk Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of a New PDE4 Inhibitor in Patients With COPD

NCT ID: NCT02986321

Last Updated: 2019-01-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

1130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-15

Study Completion Date

2018-01-09

Brief Summary

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The purpose of this study is to evaluate the dose-response relationship of different doses of CHF6001 and to identify the optimal dose (s) in terms of benefit/risk ratio for further development in the target patient population.

Detailed Description

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This is a phase II, randomized, double-blind, double-dummy, placebo and active controlled multinational, multicenter, dose ranging, 6-arm parallel-group study to identify the optimal dose of CHF6001, PDE4 inhibitor under development, with respect to lung functions and symptoms.

After a 2-wk run-in period under formoterol (Oxis Turbohaler®) and rescue salbutamol prn, patients will be randomized to one of the 6 treatment groups. After the randomization, patients will be assessed after 3, 6, 12, 18 and 24 weeks of treatment at clinic/hospital. A follow-up visit will be performed 12 days after the last visit.

During the study, patients will report daily symptoms with the EXACT-PRO/E-RS questionnaire, rescue/background medication use and compliance with the study medications. AEs, SAEs and COPD exacerbations will be monitored throughout the study. At randomization and subsequent visits, patients will undergo physical and vital signs examinations, spirometry measurement, 12-lead ECG. Symptoms and Health status will be assessed through validated questionnaires. Routine lab analysis and blood biomarkers will be done.

Conditions

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Chronic Obstructive Pulmonary Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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CHF6001 DOSE1

DOSE1

Group Type EXPERIMENTAL

CHF6001

Intervention Type DRUG

Dose response: Test one of 4 different doses of CHF6001

CHF6001 DOSE2

DOSE2

Group Type EXPERIMENTAL

CHF6001

Intervention Type DRUG

Dose response: Test one of 4 different doses of CHF6001

CHF6001 DOSE3

DOSE3

Group Type EXPERIMENTAL

CHF6001

Intervention Type DRUG

Dose response: Test one of 4 different doses of CHF6001

CHF6001 DOSE4

DOSE4

Group Type EXPERIMENTAL

CHF6001

Intervention Type DRUG

Dose response: Test one of 4 different doses of CHF6001

Matched placebo

placebo control

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

placebo control

Budesonide

Budesonide DPI 800µg

Group Type ACTIVE_COMPARATOR

Budesonide

Intervention Type DRUG

active control

Interventions

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CHF6001

Dose response: Test one of 4 different doses of CHF6001

Intervention Type DRUG

Budesonide

active control

Intervention Type DRUG

Placebo

placebo control

Intervention Type DRUG

Other Intervention Names

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Dose range finding Active comparator

Eligibility Criteria

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Inclusion Criteria

* COPD patients
* Non- childbearing potential or woman permanently sterilized or on one or more highly effective contraception
* Current/ex smokers (history \> 10 pack years)
* Post bronchodilatator FEV1 \>=30% and \<=70% predicted normal value and FEV1/FVC ratio \<0.7
* Documented history of at least 1 moderate or severe exacerbation in the 12 months prior to study entry
* Symptomatic patients (MMRC score ≥2 and a CAT score ≥10)
* Patients on daily maintenance therapy with an ICS/LABA .

Exclusion Criteria

* Diagnosis of asthma or other respiratory disorders
* Maintenance bronchodilators therapy only (eg LABA alone)
* Maintenance triple therapy.
* Occurrence of a moderate or severe COPD exacerbation within 6 weeks prior to study entry or during the run-in period.
* Patients requiring long term oxygen therapy.
* Concomitant or recent pulmonary rehabilitation programme
* Known respiratory disorders other than COPD
* Lung cancer or a history of lung cancer, active or history of cancer with less than 5 years disease free survival time
* Hypersensitivity to β2-agonist, corticosteroids, PDE4 inhibitors or any of the excipients
* Depression, generalised anxiety disorder, suicidal ideation
* Any clinically significant cardiovascular disease (IM, CHF III/IV; AF not controlled by therapy, etc) within 1 year of study entry
* Any relevant clinically significant cardiovascular condition, clinically abnormal significant 12-lead ECG (QTcF\>450 ms for male and \>470 for female) or clinically significant laboratory abnormalities
* Serum potassium value ≤3.5 mEq/L or \>5.5mEq/L and/or a fasting serum glucose value ≥140 mg/dL.
* History or symptoms of significant neurological disease
* Unstable concurrent disease: eg uncontrolled Thyroid disease or other endocrine diseases, gastrointestinal uncontrolled disease, uncontrolled immune diseases
* Renal impairment.
* Patients with abnormal alanine aminotransferase and/ or aspartate aminotransferase and/or bilirubin
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities and patients receiving treatment with any drug known to have a well defined potential for hepatotoxicity before Study entry
* Severely obese (BMI ≥35 kg/m2) or have experienced excessive weight loss recently
* History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit.
* Any recent participation to a clinical Study with other investigational drug
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dave Singh

Role: PRINCIPAL_INVESTIGATOR

Medicines Evaluation Unit, Manchester, UK

References

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Govoni M, Bassi M, Santoro D, Donegan S, Singh D. Serum IL-8 as a Determinant of Response to Phosphodiesterase-4 Inhibition in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2023 Sep 1;208(5):559-569. doi: 10.1164/rccm.202301-0071OC.

Reference Type DERIVED
PMID: 37192443 (View on PubMed)

Singh D, Emirova A, Francisco C, Santoro D, Govoni M, Nandeuil MA. Efficacy and safety of CHF6001, a novel inhaled PDE4 inhibitor in COPD: the PIONEER study. Respir Res. 2020 Sep 22;21(1):246. doi: 10.1186/s12931-020-01512-y.

Reference Type DERIVED
PMID: 32962709 (View on PubMed)

Related Links

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https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005548-32

Study Record on EU Clinical Trials Register including results

Other Identifiers

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2015-005548-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CCD-06001AA1-01

Identifier Type: -

Identifier Source: org_study_id

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