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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 11 January 2021
Main ID:  EUCTR2016-005110-22-DE
Date of registration: 23/06/2017
Prospective Registration: Yes
Primary sponsor: Santhera Pharmaceuticals (Switzerland) Ltd
Public title: A clinical study to investigate safety, tolerability and dose of orally inhaled multiple doses of POL6014 in patients with Cystic Fibrosis
Scientific title: Phase-Ib/IIa study to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of orally inhaled multiple doses of POL6014 in patients with Cystic Fibrosis
Date of first enrolment: 20/11/2017
Target sample size: 40
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-005110-22
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: no
Cross over: no
Other: yes
Other trial design description: sequential-group dose-escalation
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 3
 
Phase:  Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Germany
Contacts
Name: Anna Carratú   
Address:  Hohenrainstrasse 24 4133 Pratteln Switzerland
Telephone: +41619068917
Email: anna.carratu@santhera.com
Affiliation:  Santhera Pharmaceuticals (Switzerland) Ltd
Name: Anna Carratú   
Address:  Hohenrainstrasse 24 4133 Pratteln Switzerland
Telephone: +41619068917
Email: anna.carratu@santhera.com
Affiliation:  Santhera Pharmaceuticals (Switzerland) Ltd
Key inclusion & exclusion criteria
Inclusion criteria:
1.Patient has given written informed consent to participation in the trial prior to their enrolment and any trial-related procedure.
2.Male patients or female patients of non-childbearing potential, aged 18 to 55 years, inclusive. Women of non-childbearing potential are defined as those who have no uterus, or ligation of the fallopian tubes, or permanent cessation of ovarian function due to ovarian failure or surgical removal of the ovaries. Documentation of surgical procedure is required for patients who have had a hysterectomy or tubal ligation.
3.Men must agree to practice contraception from start of study medication up to 90 days after the last dose of the study medication.
4.Patient with a diagnosis of CF documented by a compatible clinical or radiographic presentation and laboratory criteria, more specifically, sweat or genetic testing (i.e., presence of the most common genetic defect ?F 508 or any other mutation that can produce CF).
5.Patient should confirm to produce frequently spontaneous sputum with a frequency of over 3 expectorates per day. Patient should be capable of producing a spontaneous sputum sample at screening (within a time range of approx. 3h during the screening visit).
6.Except for CF and CF-related diseases, no other significant disease as assessed by a screening examination including medical history, physical examination, vital signs, ECG assessment, pulmonary function testing (PFT), and clinical laboratory results. Deviations of clinical laboratory results can be accepted if they are in accordance with the diagnosis of CF and CF-related diseases, supposed they do not indicate a clinical state that is expected to constitute a significant additional risk.
7.Patient must have an FEV1 = 40% of predicted value at screening.
8.Body mass index (BMI) between 16.5 and 30 (both inclusive).
9.Non-smoker or ex-smoker who has stopped smoking for at least one (1) year prior to the Screening Visit.
10.Patient should be willing to refrain from caffeine- or theophylline-containing products within 24 h prior to a clinic visit for a full PK profile.
11.Ability to inhale in an appropriate manner (Patients will be trained to inhale from the eFlow® nebuliser device with a commercially available saline solution at the Screening Visit once informed consent has been obtained).
12.Patients should agree to start routine course of inhaled antibiotic cycle on the same day or not earlier than 3 days before IMP administration.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Patient with unstable lung disease, as defined by a change in treatment regimen during the preceding two (2) weeks, or a significant new finding on chest radiography (such as, but not limited to, pneumothorax, lobar/segmental collapse or consolidation), or in the opinion of the investigator, patient with a decline in pulmonary status within the last 12 months not considered a part of the usual, chronic progression of CF lung disease. Routine cyclic antibiotic treatment regimens including ”off/on” cycles are not considered to be changes to treatment regimens.
2.Patient has had an exacerbation of respiratory symptoms within the past four (4) weeks before screening/randomization that required initiation of a new or altered respiratory therapy, and, in the opinion of the investigator, the patient has not returned to a stable level of health
3.Patient with a history of lung transplantation.
4.Patient with a history of clinically significant renal, hepatic, gastrointestinal, cardiovascular and particularly respiratory disease (excluding CF and CF-related disease).
5.Patient with active gastrointestinal ulcer, history of intracranial bleedings, injuries and other bleedings.
6.Patient, as per assessment of the investigator, with severe hepatic impairment (e.g. laboratory values (ALT, AST > 3 x ULN and total bilirubin > 1.5 x ULN) or Child-Pugh-Class C could be indicative of such condition).
7.ECG abnormalities of clinical relevance (e.g., QTc according to Bazett’s formula =440 ms, PR >200 ms, or QRS =120 ms).
8.Patient with a resting heart rate in supine position <50 bpm, systolic blood pressure <100 mmHg or >140 mmHg, diastolic blood pressure <60 mmHg or >90 mmHg.
9.Proneness to orthostatic dysregulation, fainting, or blackouts.
10.Diagnosis of a tricuspid insufficiency in combination with a mean pulmonary arterial pressure (mPAP) > 25 mmHg, measured by Doppler echography, or, if no tricuspid insufficiency is detectable, any echocardiographic or clinical signs of severe pulmonary heart disease (cor pulmonale) or depending congestive heart failure.
11.History or presence of any malignancy.
12.Positive results in any of the following virology tests: human immunodeficiency virus (HIV) antibodies and antigen, Anti-hepatitis B-core antibody, hepatitis B surface antigen (HbsAg) and anti-hepatitis C virus antibody.
13.Known local or systemic hypersensitivity to any aerosol, medication or food that led to admission to an emergency room.
14.Participation in another clinical study with any investigational medicinal product (IMP) or device, before randomisation, within an interval of 5 half-lives (minimum 4 weeks) from the last use of that investigational drug.
15.Blood or plasma donation of more than 500 mL during the previous month before randomisation, as declared by the patient.
16.Mental condition rendering the patient incapable to understand the nature, scope, and possible consequences of the study.
17.Not willing to comply with all clinical study procedures.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Cystic fibrosis
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Intervention(s)

Product Name: POL6014
Pharmaceutical Form: Nebuliser solution
Pharmaceutical form of the placebo: Nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)
Secondary Objective: -To assess the pharmacokinetics (PK) in plasma, sputum and urine of up to 3 multiple ascending dose levels of inhaled POL6014 after 15 days q.d or b.i.d.; determine when steady state is reached during 15 days q.d. or b.i.d. treatment
Primary end point(s): -Proportion of patients with changes from baseline in physical examination findings
-Changes from baseline in laboratory safety assessments (clinical chemistry, haematology, urinalysis)
-Changes from baseline and pre-dose in vital signs (blood pressure, pulse, respiratory rate body temperature)
-Changes from baseline and pre-dose in ECG parameters
-Occurrence and severity of AEs
-Proportion of patients with local irritation of the nose or pharynx by visual inspection
-Proportion of patients with bronchospasm by symptoms such as dyspnoea, wheezing, chest tightness, cough
-Changes from baseline and pre-dose in lung function parameters (FEV1, FVC) by spirometry
-Changes from baseline in oxygen saturation in peripheral blood as measured by pulse oximetry.
Main Objective: -To assess the safety and tolerability of up to three multiple ascending dose levels of inhaled POL6014 after 15 days q.d. or b.i.d.
-To identify the highest tolerated dose level and associated dose regimen of inhaled POL6014 after 15 days q.d. or b.i.d. treatment.
Timepoint(s) of evaluation of this end point: -physical examination findings: screening; V1; FU
- laboratory safety assessments: screening, V2, 3, 4 and FU
-vital signs (blood pressure, pulse, respiratory rate body temperature): screening, V2, 3, 4 and FU
-ECG parameters:screening, V2, 3, 4 and FU
- Occurrence and severity of AEs: throught all the study
-Proportion of patients with local irritation of the nose or pharynx by visual inspection: V2, 3, 4
-Proportion of patients with bronchospasm by symptoms such as dyspnoea, wheezing, chest tightness, cough: throught the study
-lung function parameters (FEV1, FVC) by spirometry: screening, V2,3, 4 and FU
-oxygen saturation in peripheral blood as measured by pulse oximetry: screening, V2,3, 4 and FU
Secondary Outcome(s)
Secondary end point(s): PK parameters derived from plasma, urine and sputum concentrations of POL6014 and metabolites
Timepoint(s) of evaluation of this end point: Sputum and plasma PK samples: V2, 3, 4

Urine sample: V2 and 4
Secondary ID(s)
SNT-I-018
Source(s) of Monetary Support
Santhera Pharmaceuticals (Switzerland) Ltd
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 19/09/2017
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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