NCT02244203CompletedPhase 1
Investigation of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of 0.25, 0.5, 1, 2, 4, 20, 50, 100, 150 and 200 mg BI 60732 Powder in Bottle (PIB) Administered to Healthy Male Volunteers in a Randomised, Double Blind, Placebo Controlled Phase I Trial
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 56
- Primary Endpoint
- Number of patients with clinically relevant changes in 12-lead ECG
Study Overview
Brief Summary
Single Rising Dose (SRD) study: First evaluation of safety, tolerability, pharmacokinetics and pharmacodynamics of BI 60732
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
- •Age ≥ 18 and Age ≤ 45 years
- •BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index)
- •Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice and the local legislation
Exclusion Criteria
- •Any finding of the medical examination deviating from normal and of clinical relevance. Repeated measurement of a systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg
- •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) or psychiatric disorders or neurological disorders
- •History of relevant orthostatic hypotension, fainting spells or blackouts
- •Chronic or relevant acute infections
- •History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
- •Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration except if a relevant interaction can be ruled out
- •Participation in another trial with an investigational drug within 2 months prior to first study drug administration
- •Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
- •Alcohol abuse (average consumption of more than 30 g / day)
- •Drug abuse
- •Blood donation (more than 100 mL within four weeks prior to the start of study)
- •Any laboratory value outside the reference range that is of clinical relevance
- •Inability to comply with dietary regimen of trial site
- •A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
- •A history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)
- •Anaemia at screening
- •Subjects who in the investigator's judgement are perceived as having an increased risk of bleeding, for example because of:
- •Hemorrhagic disorders or bleeding diathesis
- •Occult blood in faeces or haematuria
- •Trauma or surgery within the last month or as long as an excessive risk of bleeding persists after these events, or planned surgery during trial participation
- •History of arteriovenous malformation or aneurysm
- •History of gastroduodenal ulcer disease or gastrointestinal haemorrhage
- •History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding
- •Use of drugs that may interfere with haemostasis during trial conduct (e.g. acetylsalicylic acid or other non-steroidal anti-inflammatory drugs)
- •Thrombocytopenia (platelet count < 100/nL)
Arms & Interventions
Single rising doses of BI 60732
Experimental
Intervention: BI 60732 (Drug)
Placebo
Placebo Comparator
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Number of patients with clinically relevant changes in 12-lead ECG
Time Frame: up to day 21 after start of treatment
Number of patients with clinically relevant changes in coagulation parameters
Time Frame: up to 72 hours after start of treatment
Parameters: * Activated partial thromboplastin time (aPTT) * Prothrombin time (PT) * HepTest®
Number of patients with clinically relevant changes in laboratory parameters
Time Frame: up to day 21 after start of treatment
Number of patients with clinically relevant changes in vital signs (blood pressure (BP), pulse rate (PR))
Time Frame: up to day 21 after start of treatment
Global assessment of tolerability by investigator on a 4-point scale
Time Frame: up to 21 days after start of treatment
Number of patients with adverse events
Time Frame: up to 6 weeks
Secondary Outcomes
- Area under the concentration-time curve of the analyte in plasma (AUC)(up to 264 hours after start of treatment)
- Terminal rate constant of the analyte in plasma (λz)(up to 264 hours after start of treatment)
- Terminal half-life of the analyte in plasma (t1/2)(up to 264 hours after start of treatment)
- Fraction of analyte eliminated in urine from time point t1 to time point t2 (fet1-t2)(up to 264 hours after start of treatment)
- Inhibition of FXa activity(Pre-dose up to 168 hours after start of treatment)
- Percentage peak inhibition of thrombin generation(up to 24 hours after start of treatment)
- Time from dosing to maximum measured concentration of the analyte in plasma (tmax)(up to 264 hours after start of treatment)
- Changes in activated partial thromboplastin time (aPTT)(Pre-dose, up to 72 hours after start of treatment)
- Prolongation of coagulation time by Heptest®(up to 72 hours after start of treatment)
- Maximum measured concentration of the analyte in plasma (Cmax)(up to 264 hours after start of treatment)
- Apparent clearance of the analyte in plasma after extravascular administration (CL/F)(up to 264 hours after start of treatment)
- Amount of analyte eliminated in urine from the time point t1 to time point t2 (Aet1-t2)(up to 264 hours after start of treatment)
- Changes in prothrombin time (PT)(Pre-dose, up to 72 hours after start of treatment)
- Relative prolongation of lag time of thrombin generation(up to 24 hours after start of treatment)
- Mean residence time of the analyte in the body after oral administration (MRTpo)(up to 264 hours after start of treatment)
- Percentage inhibition of endogenous thrombin generation(up to 24 hours after start of treatment)
- Relative prolongation of time to maximum inhibition of thrombin generation(up to 24 hours after start of treatment)
- Renal clearance of the analyte from the time point t1 until the time point t2 (CLR,t1-t2)(Pre-dose, up to 264 hours after start of treatment)
- Maximum effect (Emax)(up to 168 hours after start of treatment)
- Time to maximum effect (tmax)(up to 168 hours after start of treatment)
- Area under the effect curve (AUEC)(up to 168 hours after start of treatment)
Investigators
Similar Trials
Completed
Phase 1
Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 1060469 in Healthy Asian Male VolunteersHealthyNCT02183545Boehringer Ingelheim80
Completed
Phase 1
Safety and Pharmacokinetics of Single Rising Doses of BI 705564 and Food Effect on BI 705564 in Healthy Male SubjectsHealthyNCT03123185Boehringer Ingelheim91
Completed
Phase 1
Single Rising Dose Study of BI 690517 in Healthy VolunteersHealthyNCT02891148Boehringer Ingelheim50
Completed
Phase 1
A Phase I Study Evaluating the Safety, Tolerability, PK and PD in Healthy Chinese VolunteersHealthy Chinese VolunteersNCT03971916Harbour BioMed (Guangzhou) Co. Ltd.24
Completed
Phase 1
A Study in Healthy Men to Test How Well Different Doses of BI 1819479 Are Tolerated and Taken up by the Body With or Without FoodHealthyNCT04801693Boehringer Ingelheim66