Clinical trial NCT02217631: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 653048 BS H3PO4 Capsule Multiple Rising Doses in Healthy Male Volunteers
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (Biomarkers) of BI 653048 BS H3PO4 Capsule Formulation Administered as Multiple Doses of 25 mg to 200 mg qd for 10 Days. A Randomised, Double-blind Within Dose Groups, Placebo-controlled, Multiple Rising Dose Trial With Open-label Active Comparator
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-15
Enrollment: 140
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of the trial were to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of BI 653048 BS H3PO4 compared with prednisolone.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects based on a complete medical history, physical examination, vital signs (blood pressure and pulse rate), 12-lead ECG, and clinical laboratory tests
* Age of 18 to 50 years
* Body mass index (BMI) of 18.5 to 29.9 kg/m2
* Signed and dated written informed consent in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

* Any clinically relevant deviation from normal in the medical examination including blood pressure, pulse rate, and ECG
* Any evidence of a clinically relevant concomitant disease
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
* Surgery of the gastrointestinal tract (except appendectomy)
* Diseases of the central nervous system (such as epilepsy), psychiatric disorders, or neurological disorders
* History of relevant orthostatic hypotension, fainting spells, or blackouts
* Chronic or relevant acute infections
* History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)
* Intake of drugs with a long half-life (\>24 h) within at least 1 month or less than 10 half-lives of the respective drug before first treatment with study drug or during trial
* Use of drugs which might reasonably influence the results of the trial or which prolong the QT/QTc interval within 10 days before first treatment with study drug or during trial
* Participation in another trial with an investigational drug within 30 days before first treatment with study drug or during trial
* Smoker (more than 10 cigarettes, 3 cigars, or 3 pipes per day)
* Inability to refrain from smoking beginning from 1 day before first treatment with study drug until discharge from the clinical unit
* Alcohol abuse (more than 60 grams per day)
* Drug abuse
* Blood donation of more than 100 mL within 4 weeks before first treatment with study drug or during trial
* Excessive physical activities within 1 week before first treatment with study drug or during trial
* Any laboratory value outside the reference range and of clinical relevance
* Inability to comply with dietary regimen of trial site
* A marked baseline prolongation of the QT/QTc interval (e.g. QTc intervals that are repeatedly longer than 450 ms)
* A history of additional risk factors for torsades de points (e.g. heart failure, hypokalaemia, or family history of Long QT syndrome

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: up to day 14
measure: Number of patients with clinically significant findings in vital signs
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically significant findings in ECG
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically significant findings in laboratory tests
timeFrame: up to 10 days after last drug administration
measure: Assessment of tolerability by the investigator on a four-point scale
timeFrame: up to 10 days after last drug administration
Secondary outcomes:
measure: Maximum measured concentration of the analyte in plasma at different time points (Cmax)
timeFrame: up to day 13
measure: time from dosing to maximum measured concentration of the analyte at different time points (tmax)
timeFrame: up to day 13
measure: Area under the concentration-time curve of the analyte in the plasma over time interval from 0 to the last measurable time point of the dose at different time points (AUC0-tz)
timeFrame: up to day 13
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity at different time points (AUC0-∞)
timeFrame: up to day 13
measure: Percentage of the AUC0-∞ that is obtained by extrapolation at different time points (%AUCtz-∞)
timeFrame: up to day 13
measure: Terminal phase elimination rate constant at different time points (λz)
timeFrame: up to day 13
measure: Mean residence time of the analyte in the body after oral administration at different time points (MRTpo)
timeFrame: up to day 13
measure: Terminal phase elimination half life at different time points (t1/2)
timeFrame: up to day 13
measure: Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/Fss)
timeFrame: up to day 13
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/Fss)
timeFrame: up to day 13
measure: Minimum plasma concentration at steady state (Cmin,ss)
timeFrame: up to day 13
measure: Dose-normalized Cmax at steady state (Cmax/Dss)
timeFrame: up to day 13
measure: Dose-normalised AUC0-∞ at steady state (AUC0-∞/Dss)
timeFrame: up to day 13
measure: Accumulation index of the analyte when comparing AUCτ (RA,AUCτ)
timeFrame: up to day 13
measure: Accumulation index of the analyte when comparing Cmax (RA,Cmax)
timeFrame: up to day 13
measure: Linearity index (LI)
timeFrame: up to day 13
measure: Amount of analyte excreted in urine unchanged from t1 to t2 interval at different time points (Aet1-t2)
timeFrame: up to day 11
measure: Renal clearance of the unchanged analyte at different time points (CLr)
timeFrame: up to day 11
measure: Area under the serum biomarker concentration-time curve after the Nth dose (AUECN)
timeFrame: up to day 13
measure: Area under the baseline (before dose level) but above serum biomarker concentration-time curve after the Nth dose (AUECbelow_base)
timeFrame: up to day 13
measure: Minimum measured serum concentration of the biomarkers after the Nth dose (Emin,N)
timeFrame: up to day 13
measure: Maximum measured serum concentration of the biomarkers after the Nth dose (Emax,N)
timeFrame: up to day 13
measure: Serum biomarker concentration after the (N-1)th dose but before the Nth dose (Epre,N)
timeFrame: up to day 13
measure: Measured value of the biomarkers in biological matrix at the set time point after Nth dose (EN)
timeFrame: up to day 13
measure: Oral glucose insulin sensitivity (OGIS) index
timeFrame: up to day 13
measure: Homeostasis model assessment (HOMA) value
timeFrame: up to day 13
Other outcomes:
Locations:
Study officials:
References:
citation: Harcken C, Scholl P, Nabozny G, Thomson D, Bianchi D. Clinical profile of the functionally selective glucocorticoid receptor agonist BI 653048 in healthy male subjects. Expert Opin Investig Drugs. 2019 May;28(5):489-496. doi: 10.1080/13543784.2019.1599859. Epub 2019 Apr 9.