Clinical trial NCT01493570: Assessment of Exposure of BI 409306 in Cerebrospinal Fluid (CSF) Relative to Plasma as Well as to Evaluation of the Effect of Different Doses of BI 409306 on the cGMP (Cyclic Guanosine Monophosphate) Levels in CSF in Healthy Male Volunteers
Official title: Randomised, Double-blind, Placebo-controlled Parallel-group Proof of Mechanism Study to Assess the Pharmacokinetics and to Evaluate the Pharmacodynamic Effect of Different Single Oral Doses of BI 409306 in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-12-16
Enrollment: 20
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Due to the exploratory nature of this trial, there is no primary objective in a confirmatory sense. The study aims

- to evaluate the effect of different doses of BI 409306 on biomarker and to assess the exposure of BI 409306


Eligibility criteria: Inclusion criteria:

1. Healthy males according to the following criteria:

   Based upon a complete medical history, including the physical examination, vital signs after 10 minutes in supine position (blood pressure (BP), pulse rate (PR)), body temperature (BT)), 12-lead electrocardiogram (ECG)), clinical laboratory tests
2. Age =21 and Age =50 years
3. Body Mass Index (BMI) =18.5 and BMI =29.9 kg/m2
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and considered by the investigator as clinical relevant
2. Abnormal values for Prothrombin Time (PT), (Activated Partial Thromboplastin Time (aPTT) and thrombocytes considered by the investigator as clinically relevant
3. Any evidence of a clinically relevant concomitant disease
4. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
5. Surgery of the gastrointestinal tract (except appendectomy)
6. Diseases of the central nervous system (included but not limited to any kind of seizures, stroke or psychiatric disorders)
7. History of relevant orthostatic hypotension, fainting spells or blackouts.
8. Chronic or relevant acute infections
9. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
10. Intake of 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
11. 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
12. Participation in another trial with an investigational drug within two months prior to administration or during the trial
13. Smoker, who consume more than 5 cigarettes per day
14. Inability to refrain from smoking on trial days
15. Alcohol abuse (more than 20 g/day): 2 units/day (14 units/week)
16. Drug abuse
17. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
18. Excessive physical activities (within one week prior to administration or during the trial)
19. Any laboratory value outside the reference range that is of clinical relevance
20. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF interval \>450 ms)
21. Inability to understand and to comply with protocol requirements and restrictions and dietary regimen of trial site
22. of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
23. Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until three month after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female (intra-uterine device with spermicide, hormonal contraceptive since at least two months)

Primary outcomes:
measure: Ratio of Cmax of BI 409306 in CSF Compared to Plasma
timeFrame: Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail).
measure: Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax)
timeFrame: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
measure: Maximum Relative Change From Baseline of cGMP in CSF
timeFrame: Within 2:00 hours (h):minutes(min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00h, 4:00, 6:00, 8:00h, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
measure: Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF
timeFrame: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Secondary outcomes:
measure: Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax)
timeFrame: Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail).
measure: Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax)
timeFrame: Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail).
measure: Maximum Measured cGMP Concentration in CSF (Cmax)
timeFrame: Within 2:00 hours (h): minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
measure: Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax)
timeFrame: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: 1289.3.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: