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NCT01505894

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses

Completed Phase 1 Results posted Last updated 8 March 2024
What this trial tests

Phase 1 trial testing BI 409306 in Healthy in 83 participants. Completed in 1 July 2012.

Timeline
1 January 2012
Primary endpoint
1 July 2012
1 July 2012

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsingle group
Maskingdouble
Primary purposetreatment
Enrollment83
Start date1 January 2012
Primary completion1 July 2012
Estimated completion1 July 2012
Sites1 location across Germany

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 21 to 80, any sex, with Healthy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Concentration of BI 409306 in Plasma (Cmax) Secondary · 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 measured concentration of the BI 409306 in plasma after first dose.

GroupValue95% CI
BI 409306 25 Milligram- Young Subjects (QD)245± 130
BI 409306 25 Milligram- Elderly Subjects (QD)376± 48.0
BI 409306 50 Milligram- Young Subjects (QD)565± 84.6
BI 409306 50 Milligram- Young Subjects (BID)696± 47.8
BI 409306 50 Milligram- Elderly Subjects (QD)1100± 58.5
BI 409306 100 Milligram- Young Subjects (QD)1030± 79.2
BI 409306 100 Milligram- Elderly Subjects (QD)1840± 68.1
Time From Dosing to Maximum Measured Concentration of BI 409306 in Plasma (Tmax) Secondary · 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) after the first dose.

GroupValue95% CI
BI 409306 25 Milligram- Young Subjects (QD)0.7500.500 – 1.52
BI 409306 25 Milligram- Elderly Subjects (QD)0.5000.167 – 0.750
BI 409306 50 Milligram- Young Subjects (QD)0.5000.333 – 0.750
BI 409306 50 Milligram- Young Subjects (BID)0.7500.333 – 0.750
BI 409306 50 Milligram- Elderly Subjects (QD)0.3330.167 – 1.00
BI 409306 100 Milligram- Young Subjects (QD)0.5000.333 – 0.750
BI 409306 100 Milligram- Elderly Subjects (QD)0.5000.333 – 1.50
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) Secondary · 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 after first dose.

GroupValue95% CI
BI 409306 25 Milligram- Young Subjects (QD)548± 142
BI 409306 25 Milligram- Elderly Subjects (QD)594± 48.6
BI 409306 50 Milligram- Young Subjects (QD)955± 97.6
BI 409306 50 Milligram- Young Subjects (BID)1140± 54.0
BI 409306 50 Milligram- Elderly Subjects (QD)1510± 70.5
BI 409306 100 Milligram- Young Subjects (QD)1620± 60.1
BI 409306 100 Milligram- Elderly Subjects (QD)2840± 56.1
Maximum Concentration of BI 409306 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) Secondary · 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.

Maximum measured concentration of the BI 409306 in plasma at steady state over a uniform dosing interval τ after last dose.

GroupValue95% CI
BI 409306 25 Milligram- Young Subjects (QD)348± 71.4
BI 409306 25 Milligram- Elderly Subjects (QD)444± 44.2
BI 409306 50 Milligram- Young Subjects (QD)663± 98.0
BI 409306 50 Milligram- Young Subjects (BID)596± 42.8
BI 409306 50 Milligram- Elderly Subjects (QD)1250± 76.6
BI 409306 100 Milligram- Young Subjects (QD)1260± 55.4
BI 409306 100 Milligram- Elderly Subjects (QD)2150± 87.0
Time to Achieve Maximum Concentration of BI 409306 in Plasma at Steady State (Tmax,ss) Secondary · 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 from last dosing until the maximum concentration of the analyte in plasma is reached at steady state after last dose on day 14.

GroupValue95% CI
BI 409306 25 Milligram- Young Subjects (QD)0.7500.333 – 0.783
BI 409306 25 Milligram- Elderly Subjects (QD)0.5000.333 – 0.750
BI 409306 50 Milligram- Young Subjects (QD)0.6250.333 – 1.02
BI 409306 50 Milligram- Young Subjects (BID)0.7500.500 – 1.00
BI 409306 50 Milligram- Elderly Subjects (QD)0.4170.167 – 1.50
BI 409306 100 Milligram- Young Subjects (QD)0.5000.333 – 0.750
BI 409306 100 Milligram- Elderly Subjects (QD)0.3330.167 – 1.50
Area Under the Concentration-time Curve of BI 409306 in Plasma at Steady State (AUCτ,ss) Secondary · 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.

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.

GroupValue95% CI
BI 409306 25 Milligram- Young Subjects (QD)747± 93.1
BI 409306 25 Milligram- Elderly Subjects (QD)621± 55.8
BI 409306 50 Milligram- Young Subjects (QD)1070± 125
BI 409306 50 Milligram- Young Subjects (BID)1100± 52.4
BI 409306 50 Milligram- Elderly Subjects (QD)1710± 83.6
BI 409306 100 Milligram- Young Subjects (QD)1960± 64.3
BI 409306 100 Milligram- Elderly Subjects (QD)3990± 119
Number of Young and Elderly Subjects With On-treatment Adverse Events by Treatment Group Primary · From first drug administration until the end-of-trial examination, up to 28 days.

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.

GroupValue95% CI
Placebo- Young Subjects6
Placebo-Elderly Subjects Once Daily (QD)3
BI 409306 25 Milligram- Young Subjects (QD)5
BI 409306 25 Milligram- Elderly Subjects (QD)6
BI 409306 50 Milligram- Young Subjects (QD)4
BI 409306 50 Milligram- Young Subjects (BID)8
BI 409306 50 Milligram- Elderly Subjects (QD)5
BI 409306 100 Milligram- Young Subjects (QD)8
BI 409306 100 Milligram- Elderly Subjects (QD)8
Number of Participants With Clinically Relevant Abnormal Findings in Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Physical Examination, Ophthalmological Examination and Suicidality Assessment Primary · From first drug administration until the end-of-trial examination, up to 28 days.

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.

Vital signs
GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
12-lead ECG
GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Clinical laboratory test
GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Physical examiniation
GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Ophthalmological examination
GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Suicidality assessment
GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Number of Participants Per Category of Global Tolerability Assessed by the Investigator Primary · From first drug administration until the end-of-trial examination, up to 28 days.

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.

GroupValue95% CI
Placebo- Young Subjects11
Placebo-Elderly Subjects Once Daily (QD)9
BI 409306 25 Milligram- Young Subjects (QD)9
BI 409306 25 Milligram- Elderly Subjects (QD)9
BI 409306 50 Milligram- Young Subjects (QD)9
BI 409306 50 Milligram- Young Subjects (BID)9
BI 409306 50 Milligram- Elderly Subjects (QD)8
BI 409306 100 Milligram- Young Subjects (QD)9
BI 409306 100 Milligram- Elderly Subjects (QD)8
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)1
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Number of Participants With Abnormal Findings in Color Discrimination Test Primary · From first drug administration until the end-of-trial examination, up to 28 days.

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.

GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)1
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)0
Number of Participants With Abnormal Findings in Visual Acuity Test Primary · From first drug administration until the end-of-trial examination, up to 28 days.

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.

GroupValue95% CI
Placebo- Young Subjects0
Placebo-Elderly Subjects Once Daily (QD)0
BI 409306 25 Milligram- Young Subjects (QD)0
BI 409306 25 Milligram- Elderly Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (QD)0
BI 409306 50 Milligram- Young Subjects (BID)0
BI 409306 50 Milligram- Elderly Subjects (QD)0
BI 409306 100 Milligram- Young Subjects (QD)0
BI 409306 100 Milligram- Elderly Subjects (QD)1

Adverse events — posted to ClinicalTrials.gov

Time frame: From first drug administration until the end-of-trial examination, up to 28 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo- Young Subjects
Serious: 0/12 (0%)
Deaths: 0/12
Placebo-Elderly Subjects Once Daily (QD)
Serious: 0/9 (0%)
Deaths: 0/9
BI 409306 25 Milligram- Young Subjects (QD)
Serious: 0/9 (0%)
Deaths: 0/9
BI 409306 25 Milligram- Elderly Subjects (QD)
Serious: 0/9 (0%)
Deaths: 0/9
BI 409306 50 Milligram- Young Subjects (QD)
Serious: 0/9 (0%)
Deaths: 0/9
BI 409306 50 Milligram- Young Subjects (BID)
Serious: 0/9 (0%)
Deaths: 0/9
BI 409306 50 Milligram- Elderly Subjects (QD)
Serious: 0/8 (0%)
Deaths: 0/8
BI 409306 100 Milligram- Young Subjects (QD)
Serious: 0/9 (0%)
Deaths: 0/9
BI 409306 100 Milligram- Elderly Subjects (QD)
Serious: 0/9 (0%)
Deaths: 0/9
Other adverse events (38 terms — click to expand)

ReactionSystemPlacebo- Young SubjectsPlacebo-Elderly Subjects O…BI 409306 25 Milligram- Yo…BI 409306 25 Milligram- El…BI 409306 50 Milligram- Yo…BI 409306 50 Milligram- Yo…BI 409306 50 Milligram- El…BI 409306 100 Milligram- Y…BI 409306 100 Milligram- E…
PhotophobiaEye disorders
PhotopsiaEye disorders
Vision blurredEye disorders
HeadacheNervous system disorders
ChromatopsiaEye disorders
Visual impairmentEye disorders
Dry mouthGastrointestinal disorders
FlatulenceGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
DizzinessNervous system disorders
ParaesthesiaNervous system disorders
RashSkin and subcutaneous tissue disorders
Cerumen impactionEar and labyrinth disorders
Abnormal sensation in eyeEye disorders
AsthenopiaEye disorders
Eye painEye disorders
DiarrhoeaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Faeces hardGastrointestinal disorders
Oedema peripheralGeneral disorders
RhinitisInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
AnxietyPsychiatric disorders
NervousnessPsychiatric disorders
Withdrawal syndromePsychiatric disorders
DysmenorrhoeaReproductive system and breast disorders
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Nasal drynessRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT01505894 adverse events section.

Sponsor's own description

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

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing