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

NCT01493570 | Completed Phase 1 Results

• 2 other identifiers: 1289.32011-003749-16
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Ratio of Cmax of BI 409306 in CSF Compared to Plasma

  Ratio of Cmax (maximum measured concentration) of BI 409306 in Cerebrospinal fluid (CSF) compared to plasma is presented. Ratio was calculated as: Cmax of BI 409306 in CSF/ Cmax of BI 409306 in plasma. Time frame: Blood: Within 2:00 hours (h):minutes (min) before dosing and 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. CSF: 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.

  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).

• Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax)

  The maximum change from baseline of cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF) was calculated as: exp(ln(cGMPmax) - ln(cGMP0)), where cGMP0 is the baseline cGMP value per subject (mean of the two pre-dose measurements) and cGMPmax is the maximal cGMP value per subject measured after drug intake.

  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.

• Maximum Relative Change From Baseline of cGMP in CSF

  Maximum relative change from baseline of cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF) is presented. Maximum relative change from baseline was calculated as: (cGMPmax - cGMP0)/ cGMP0, where cGMPmax is the maximum measured concentration of cGMP after dosing of BI 409306 and cGMP0 is cGMP concentration at baseline.

  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.

• Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF

  Maximum (absolute) change from baseline of cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) is presented. The maximum (absolute) change from baseline in cGMP concentration was calculated as: maximum measured concentration of cGMP after dosing of BI 409306 (cGMPmax) - cGMP concentration at baseline (cGMP0).

  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 (4)

• Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax)

  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).

• Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax)

  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).

• Maximum Measured cGMP Concentration in CSF (Cmax)

  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.

• Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax)

  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.

Study Arms (5)

BI 409306 25mg

EXPERIMENTAL

Drug: BI 409306

BI 409306 50 mg

EXPERIMENTAL

Drug: BI 409306

BI 409306 100 mg

EXPERIMENTAL

Drug: BI 409306

BI 409306 200 mg

EXPERIMENTAL

Drug: BI 409306

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI 409306 DRUG

Film-coated tablet

BI 409306 100 mg; BI 409306 200 mg; BI 409306 25mg; BI 409306 50 mg

Placebo DRUG

Film-coated tablet

Placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Age =21 and Age =50 years
• Body Mass Index (BMI) =18.5 and BMI =29.9 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

You may not qualify if:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and considered by the investigator as clinical relevant
• Abnormal values for Prothrombin Time (PT), (Activated Partial Thromboplastin Time (aPTT) and thrombocytes considered by the investigator as clinically relevant
• 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 (included but not limited to any kind of seizures, stroke or psychiatric 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 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
• 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
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker, who consume more than 5 cigarettes per day
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 20 g/day): 2 units/day (14 units/week)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1289.3.1 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

Location

Related Links

• Related Info

MeSH Terms

Interventions

BI 409306

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 16, 2011
• Study Start: December 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 21, 2012
• Last Updated: March 21, 2024
• Results First Posted: March 21, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)