Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses

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)

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 409306

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany
    • 1289.2.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo - Young Subjects	Drug: Placebo; Film-coated tablet
Placebo Comparator: Placebo - Elderly Subjects	Drug: Placebo; Film-coated tablet
Experimental: BI 409306 25 mg - Young Subjects QD; 25 milligram (mg) of BI 409306 were administered in young subjects once daily (QD).	Drug: BI 409306; Film-coated tablet
Experimental: BI 409306 25 mg - Elderly Subjects QD; 25 mg of BI 409306 were administered in elderly subjects once daily (QD).	Drug: BI 409306; Film-coated tablet
Experimental: BI 409306 50 mg - Young Subjects QD; 50 mg of BI 409306 were administered in young subjects once daily (QD).	Drug: BI 409306; Film-coated tablet
Experimental: BI 409306 50 mg - Young Subjects BID; 50 mg of BI 409306 were administered in young subjects twice daily (BID).	Drug: BI 409306; Film-coated tablet
Experimental: BI 409306 50 mg - Elderly Subjects QD; 50 mg of BI 409306 were administered in elderly subjects once daily	Drug: BI 409306; Film-coated tablet
Experimental: BI 409306 100 mg - Young Subjects QD; 100 mg of BI 409306 were administered in young subjects once daily (QD).	Drug: BI 409306; Film-coated tablet
Experimental: BI 409306 100 mg - Elderly Subjects QD; 100 mg of BI 409306 were administered in elderly subjects once daily (QD).	Drug: BI 409306; Film-coated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Young and Elderly Subjects With On-treatment Adverse Events by Treatment Group	An adverse event is defined as any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product.	From first drug administration until the end-of-trial examination, up to 28 days.
Number of Participants With Clinically Relevant Abnormal Findings in Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Physical Examination, Ophthalmological Examination and Suicidality Assessment	Number of participants with clinically relevant abnormal findings, as judged by investigator and reported as adverse event (AE), in vital signs (blood pressure, pulse rate, orthostatic test), 12-lead electrocardiogram (ECG), clinical laboratory tests (haematology, clinical chemistry, urinalysis) , physical examination, ophthalmological examination and suicidality assessment.	From first drug administration until the end-of-trial examination, up to 28 days.
Number of Participants Per Category of Global Tolerability Assessed by the Investigator	The investigator assessed tolerability based on adverse events and the laboratory evaluation and classified the overall tolerability according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'. Investigator judgement based on clinical findings: "good" - No or mild adverse events (AEs) and no clinically significant (NCS) findings in any clinical assessments; "satisfactory" - mild or moderate AEs, NCS clinical findings; "not satisfactory" - moderate/severe AEs and/or clinically significant (CS) findings.	From first drug administration until the end-of-trial examination, up to 28 days.
Number of Participants With Abnormal Findings in Color Discrimination Test	Color vision was tested using the Ishihara test for color deficiency. The test consisted of a number of plates, called Ishihara plates, each of which contains a circle of dots of differing color and size. Within the pattern some dots form a number visible to those with normal color vision and invisible, or difficult to see, for those with a color vision deficiency. Participants with abnormal findings in color discrimination test are participants, who are not able to recognize the sign on the presented table.	From first drug administration until the end-of-trial examination, up to 28 days.
Number of Participants With Abnormal Findings in Visual Acuity Test	Snellen chart was used to measure visual acuity. It measures the smallest line that a participant was able to read at a distance of 3 meter. Participants with abnormal findings in visual acuity test are participants, who are not able to recognize the letters on the line 3.	From first drug administration until the end-of-trial examination, up to 28 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration of BI 409306 in Plasma (Cmax)	Maximum measured concentration of the BI 409306 in plasma after first dose.	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.
Time From Dosing to Maximum Measured Concentration of BI 409306 in Plasma (Tmax)	Time from dosing to maximum measured concentration of BI 409306 in plasma (Tmax) after the first dose.	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.
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 extrapolated to infinity after first dose.	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.
Maximum Concentration of BI 409306 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)	Maximum measured concentration of the BI 409306 in plasma at steady state over a uniform dosing interval τ after last dose.	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.
Time to Achieve Maximum Concentration of BI 409306 in Plasma at Steady State (Tmax,ss)	Time from last dosing until the maximum concentration of the analyte in plasma is reached at steady state after last dose on day 14.	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.
Area Under the Concentration-time Curve of BI 409306 in Plasma at Steady State (AUCτ,ss)	This endpoint calculates area under the concentration-time curve of BI 409306 in plasma at steady state over a uniform dosing interval τ after last dose on day 14.	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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: January 5, 2012
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (Estimated): January 9, 2012

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; BI 409306
• Other Study ID Numbers: 1289.2; 2011-002369-39 (EudraCT Number: EudraCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency