Clinical trial NCT03422068: This Study Tests Different Doses of BI 1015550 in Patients With Idiopathic Pulmonary Fibrosis (IPF). The Study Tests How BI 1015550 is Taken up by the Body and How Well it is Tolerated.
Official title: Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 1015550 in Patients With Idiopathic Pulmonary Fibrosis (IPF) on no Background Anti-fibrotic Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2018-02-05
Enrollment: 15
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to investigate safety and tolerability of BI 1015550 in patients with IPF.

The secondary objectives are to evaluate the pharmacokinetics (PK) of BI 1015550 in patients with IPF.


Eligibility criteria: Inclusion Criteria:

* Signed and dated written informed consent prior to admission to the study in accordance with ICH Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local legislation
* Male or female patients aged ≥40 years at visit 1.
* A clinical diagnosis of IPF based on ATS/ERS/JRS/ALAT 2011 guideline within the previous 5 years as confirmed by the investigator based on chest high-resolution computed tomography (HRCT) scan taken within 12 months of visit 1 and confirmed by central review prior to visit 2.
* Forced Vital Capacity (FVC) ≥50% of predicted normal at visit 1
* Diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for haemoglobin \[Hb\] \[Visit 1\]): \> 30% of predicted normal at visit 1

Exclusion Criteria:

* Patients with a significant disease or condition other than IPF which in the opinion of the investigator, may put the patient at risk because of participation, interfere with study procedures, or cause concern regarding the patient's ability to participate in the study.
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
* Surgery of the GI tract that could interfere with PK of the trial medication (except appendectomy)
* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders including but not limited to mood disorders.
* Evidence of active infection (chronic or acute) based on clinical exam or laboratory findings.
* History of allergy or hypersensitivity to the trial medication or its excipients
* Use of drugs within 30 days prior to administration of trial medication that are known to influence the results of the trial including time between start of the Q-wave and the end of the T-wave in an electrocardiogram (QT) / QT interval corrected for heart rate using the method of Fridericia (QTcF) or Bazett (QTcB) (QTc)
* A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males or repeatedly greater than 470 ms in females) or any other relevant ECG finding at screening
* A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
* Participation in another trial where an investigational drug has been administered within 30 days or less than 5 half-lives (whichever is greater) of the respective drug prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug.
* Inability to refrain from smoking on trial days
* Alcohol abuse (consumption of more than 20 g per day)
* Active drug abuse
* Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
* Inability to comply with dietary regimen required for the trial
* Patient is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
* Male patients who do not agree to minimize the risk of female partners becoming pregnant from first dosing day until two months after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive used for at least two months prior), true sexual abstinence (when this is in line with the preferred and usual lifestyle of the patient), or surgically sterilized, including vasectomy.
* Females who are not surgically sterilised or who are not postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of Follicle-stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory).
* Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC \<0.7) at visit 1
* Patients who have previously been treated with nintedanib or pirfenidone within 30 days of visit 1.
* Positive fecal occult blood (no retest allowed),
* Positive testing for hematuria if confirmed by microscopic urine analysis (retest allowed)
* Any lifetime history of suicidal behavior (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior)
* Any suicidal ideation of type 2 to 5 on the C-SSRS in the past 12 months (i.e. active suicidal thought without method, intent or plan; active suicidal thought with method, but without intent or plan; active suicidal thought with method and intent but without specific plan; or active suicidal thought with method, intent and plan).

Primary outcomes:
measure: Safety and tolerability of BI 1015550 by the percentage of patients with drug-related AEs on-treatment
timeFrame: Up to 35 days
Secondary outcomes:
measure: AUCτ,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose)
timeFrame: Day 1
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: Day 1
measure: AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: Day 14
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over
timeFrame: Day 14
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: HYKS Keuhkosairauksien tutkimusyksikkö
city: Turku
country: Finland
facility: TYKS, Keuhkosairauksien klinikka, Turku
city: Hannover
country: Germany
facility: Fraunhofer ITEM
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Roma
country: Italy
facility: Policlinico Gemelli
city: Nieuwegein
country: Netherlands
facility: St. Antonius ziekenhuis, locatie Nieuwegein
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: