Clinical trial NCT01505894: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses
Official title: Safety, Tolerability Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses of BI 409306 Film-coated Tablets Given Orally q.d. or Bid for 14 Days in Young Healthy and Elderly Healthy Male/Female Volunteers (Randomised, Double-blind, Placebo Controlled Within Dose Groups Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-01-09
Enrollment: 83
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial was to investigate safety and tolerability of multiple doses of BI 409306 in healthy young and elderly volunteers.

The secondary objective was to explore the pharmacokinetics and pharmacodynamics of multiple doses of BI 409306 in healthy young and elderly volunteers


Eligibility criteria: Inclusion criteria:

1. Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
2. Age \>21 and Age \<50 years for young healthy volunteers or Age \>65 and Age \<80 years for elderly healthy volunteers
3. BMI \>18.5 and BMI \<29.9 kg/m2 (Body Mass Index)
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.
5. For female subjects: Female subjects must be surgically sterilized or postmenopausal. Surgical sterilization or hysterectomy must have occurred at least 6 months prior to screening. Menopausal women must have no regular menstrual bleeding for at least 2 years prior to screening.

Exclusion criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system (including but not limited to any kind of seizures, stroke or psychiatric disorders)
6. History or evidence of relevant orthostatic reaction (drop in systolic blood pressure (SBP) \>20 mm Hg and increase in heart rate \> 30 bpm after 2 minutes standing relative to supine data), fainting spells or blackouts.
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
9. Intake of any drugs within 14 days or drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
10. Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
11. Participation in another trial with an investigational drug within four weeks prior to administration or during the trial
12. Smoker (\> 5 cigarettes or \> 1 cigars or \> 1 pipes/day)
13. Inability to refrain from smoking on trial days
14. Alcohol abuse (more than 20 g/day)
15. Drug abuse
16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
17. Excessive physical activities (within one week prior to administration or during the trial)
18. Any laboratory value outside the reference range that is of clinical relevance in the judgment of investigator
19. Inability to comply with dietary regimen of trial site
20. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc F interval \>430 ms in males and \>450 ms in females);
21. A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);

Primary outcomes:
measure: Number of Young and Elderly Subjects With On-treatment Adverse Events by Treatment Group
timeFrame: From first drug administration until the end-of-trial examination, up to 28 days.
measure: Number of Participants With Clinically Relevant Abnormal Findings in Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Physical Examination, Ophthalmological Examination and Suicidality Assessment
timeFrame: From first drug administration until the end-of-trial examination, up to 28 days.
measure: Number of Participants Per Category of Global Tolerability Assessed by the Investigator
timeFrame: From first drug administration until the end-of-trial examination, up to 28 days.
measure: Number of Participants With Abnormal Findings in Color Discrimination Test
timeFrame: From first drug administration until the end-of-trial examination, up to 28 days.
measure: Number of Participants With Abnormal Findings in Visual Acuity Test
timeFrame: From first drug administration until the end-of-trial examination, up to 28 days.
Secondary outcomes:
measure: Maximum Concentration of BI 409306 in Plasma (Cmax)
timeFrame: On day 1, at -2:00 hours (pre dose) and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 hours after the first dose.
measure: Time From Dosing to Maximum Measured Concentration of BI 409306 in Plasma (Tmax)
timeFrame: On day 1, at -2:00 hours (pre-dose) and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 hours after the first dose.
measure: Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: On day 1, at -2:00 hours (pre-dose) and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 hours after the first dose.
measure: Maximum Concentration of BI 409306 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
timeFrame: At 312:00 hours (pre dose) and at 312:10 , 312:20, 312:30, 312:45, 313:00, 313:30, 314:00, 314:30, 315:00, 316:00, 318:00, 320:00, 322:00, 324:00, 326:00, 336:00, 360:00, 384:00 hours post dose, for once daily and twice daily treatment.
measure: Time to Achieve Maximum Concentration of BI 409306 in Plasma at Steady State (Tmax,ss)
timeFrame: At 312:00 hours (pre dose) and at 312:10 , 312:20, 312:30, 312:45, 313:00, 313:30, 314:00, 314:30, 315:00, 316:00, 318:00, 320:00, 322:00, 324:00, 326:00, 336:00, 360:00, 384:00 hours post dose, for once daily and twice daily treatment.
measure: Area Under the Concentration-time Curve of BI 409306 in Plasma at Steady State (AUCτ,ss)
timeFrame: At 312:00 hours (pre dose) and at 312:10 , 312:20, 312:30, 312:45, 313:00, 313:30, 314:00, 314:30, 315:00, 316:00, 318:00, 320:00, 322:00, 324:00, 326:00, 336:00, 360:00, 384:00 hours post dose, for once daily and twice daily treatment.
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: 1289.2.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: