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CompletedNCT02248259Updated Apr 25, 2024Results posted

Drug Drug Interaction Trial With Strong CYP3A4 Inhibitor (Itraconazole) in CYP2C19 Extensive Metabolizers and Poor Metabolizers

A Phase 1 interventional study of BI 409306 and Itraconazole in Healthy, sponsored by Boehringer Ingelheim. Completed at 1 site in Korea, Republic of. Open to male participants aged 20 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-04-25.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
25
Allocation
Randomized
Ages
20 Years to 45 Years
Sex
Male
01

Study summary

The objective of the current study is to evaluate the effect of once daily itraconazole on the pharmacokinetics of BI 409306 in poor (PM) and extensive metabolisers (EM) of CYP2C19.

02

Conditions studied

  • Healthy
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 45 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  • Healthy CYP2C19 genotyped male volunteers according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR, respiratory rate, body temperature), 12-lead ECG, ophthalmologic exam, clinical laboratory tests
  • Korean ethnicity according to the following criteria: be a current Korean passport or national identification card holder, and have parents and grandparents who were all born in Korea
  • Age 20 or older than 20 and 45 or younger than 45 years
  • BMI (Body Mass Index) 18.5 or more than 18.5 and BMI 25 or less than 25 kg/m2
  • Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

Exclusion criteria

Exclusion criteria:

  • Any finding of the medical examination (including BP, PR, respiratory rate, body temperature and ECG) deviating from normal and of clinical relevance
  • 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, hernia surgery)
  • Diseases of the central nervous system (including but not limited to any kind of seizures, migraine, stroke or psychiatric disorders) within the past 6 month
  • 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 (longer than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
  • 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 (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)
  • Inability to refrain from smoking on trial days
  • Alcohol abuse (more than 20 g/day)
  • Drug abuse
  • Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
  • Excessive physical activities (within one week prior to administration or during the trial)
  • Any laboratory value outside the reference range that is of clinical relevance
  • Inability to comply with dietary regimen of trial site
  • A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval more than 450 ms)
  • A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  • Abnormality on color vision test or any other finding on ophthalmologic exam that is clinically deemed to potentially interfere with the safety assessment of this trial
  • Subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until two month after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least two month)
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    Extensive Metabolisers: Ref / Test

    Participants who were extensive metabolisers received two treatments in a randomised order, the treatments were: * Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1). * Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1.

    Drug: BI 409306 · Drug: Itraconazole

  • Experimental
    Poor Metabolisers: Ref / Test

    Participants who were poor metabolisers received two treatments in a randomised order, the treatments were: * Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1). * Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1.

    Drug: BI 409306 · Drug: Itraconazole

  • Experimental
    Extensive Metabolisers: Test / Ref

    Participants who were extensive metabolisers received two treatments in a randomised order, the treatments were: * Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1. * Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1).

    Drug: BI 409306 · Drug: Itraconazole

  • Experimental
    Poor Metabolisers: Test / Ref

    Participants who were poor metabolisers received two treatments in a randomised order, the treatments were: * Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1. * Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1).

    Drug: BI 409306 · Drug: Itraconazole

Interventions

  • DrugBI 409306

    Oral single dose of BI 409306

  • DrugItraconazole

    Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole

06

What researchers measure

Primary outcomes

  1. AUC0-infinity of BI 409306 and Its Metabolites

    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) of BI 409306 and its metabolites CD 13896 and CD 14084

    Time frame: 1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration

  2. Cmax of BI 409306 and Its Metabolites

    Maximum measured concentration of the analyte in plasma (Cmax) of BI 409306 and its metabolites CD 13896 and CD 14084

    Time frame: 1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration

Secondary outcomes

  1. AUC0-tz of BI 409306 and Its Metabolites

    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable plasma concentration (AUC0-tz) of BI 409306 and its metabolites CD 13896 and CD 14084

    Time frame: 1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration

  2. Tmax of BI 409306 and Its Metabolites

    Time from dosing to the maximum concentration of the analyte in plasma (tmax) of BI 409306 and its metabolites CD 13896 and CD 14084

    Time frame: 1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration

  3. t1/2 of BI 409306 and Its Metabolites

    Terminal half-life of the analyte in plasma (t1/2) of BI 409306 and its metabolites CD 13896 and CD 14084

    Time frame: 1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration

07

Results

Posted Mar 8, 2024

Participant flow

A randomised, open-label, 2-way crossover trial. The two treatment periods were separated by a washout period of at least 3 weeks.

Treatment Period 1
Participant flow — Treatment Period 1
MilestoneExtensive Metabolisers: Ref / TestPoor Metabolisers: Ref / TestExtensive Metabolisers: Test / RefPoor Metabolisers: Test / Ref
Started6676
Completed6666
Not completed0010
Withdrew: Adverse event0010
Treatment Period 2
Participant flow — Treatment Period 2
MilestoneExtensive Metabolisers: Ref / TestPoor Metabolisers: Ref / TestExtensive Metabolisers: Test / RefPoor Metabolisers: Test / Ref
Started6666
Completed6666
Not completed0000

Outcome measures

PrimaryAUC0-infinity of BI 409306 and Its Metabolites

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) of BI 409306 and its metabolites CD 13896 and CD 14084

Time frame:
1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
Reported as:
Geometric mean · nanomole (nmol)*hour (h) /Liter (L)
AUC0-infinity of BI 409306 and Its Metabolites
nanomole (nmol)*hour (h) /Liter (L)Extensive Metabolisers: Ref. TreatmentExtensive Metabolisers: Test TreatmentPoor Metabolisers: Ref. TreatmentPoor Metabolisers: Test Treatment
BI 409306547 ± 71.6621 ± 68.81560 ± 45.51370 ± 39.4
CD 13896389 ± 26.4347 ± 19.2178 ± 20.0165 ± 14.3
CD 140842120 ± 10.92110 ± 12.61810 ± 15.71890 ± 14.2
Statistical analysis
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 113.60 · 90% CI 100.522 to 128.376Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 87.98 · 90% CI 77.839 to 99.452Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 89.21 · 90% CI 84.636 to 94.021Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 92.89 · 90% CI 88.592 to 97.396Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 99.61 · 90% CI 95.796 to 103.584Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 104.37 · 90% CI 98.783 to 110.278Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
PrimaryCmax of BI 409306 and Its Metabolites

Maximum measured concentration of the analyte in plasma (Cmax) of BI 409306 and its metabolites CD 13896 and CD 14084

Time frame:
1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
Reported as:
Geometric mean · nmol/L
Cmax of BI 409306 and Its Metabolites
nmol/LExtensive Metabolisers: Ref. TreatmentExtensive Metabolisers: Test TreatmentPoor Metabolisers: Ref. TreatmentPoor Metabolisers: Test Treatment
BI 409306264 ± 67.8246 ± 60.2564 ± 50.5432 ± 35.4
CD 13896139 ± 41.6110 ± 35.544.9 ± 33.342.8 ± 16.2
CD 14084714 ± 21.5620 ± 19.1470 ± 35.8505 ± 20.3
Statistical analysis
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 93.26 · 90% CI 80.377 to 108.217Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 76.65 · 90% CI 60.482 to 97.141Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 78.71 · 90% CI 67.304 to 92.052Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 95.29 · 90% CI 81.092 to 111.964Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 86.79 · 90% CI 80.731 to 93.309Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 107.45 · 90% CI 91.764 to 125.812Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
SecondaryAUC0-tz of BI 409306 and Its Metabolites

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable plasma concentration (AUC0-tz) of BI 409306 and its metabolites CD 13896 and CD 14084

Time frame:
1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
Reported as:
Geometric mean · nmol*h/L
AUC0-tz of BI 409306 and Its Metabolites
nmol*h/LExtensive Metabolisers: Ref. TreatmentExtensive Metabolisers: Test TreatmentPoor Metabolisers: Ref. TreatmentPoor Metabolisers: Test Treatment
BI 409306546 ± 71.6620 ± 68.81560 ± 45.51370 ± 39.4
CD 13896388 ± 26.7345 ± 19.4176 ± 20.0163 ± 14.3
CD 140842120 ± 11.02110 ± 12.61810 ± 15.71890 ± 14.2
Statistical analysis
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 113.61 · 90% CI 100.505 to 128.427Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 87.91 · 90% CI 77.763 to 99.370Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 89.05 · 90% CI 84.478 to 93.859Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 92.48 · 90% CI 88.278 to 96.889Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
  • Extensive Metabolisers: Ref. Treatment vs Extensive Metabolisers: Test Treatment · Geometric mean ratio (%): 99.61 · 90% CI 95.791 to 103.583Ratio calculated as extensive metabolisers test treatment divided by extensive metabolisers: ref. treatment
  • Poor Metabolisers: Ref. Treatment vs Poor Metabolisers: Test Treatment · Geometric mean ratio (%): 104.44 · 90% CI 98.861 to 110.336Ratio calculated as poor metabolisers test treatment divided by poor metabolisers: ref. treatment
SecondaryTmax of BI 409306 and Its Metabolites

Time from dosing to the maximum concentration of the analyte in plasma (tmax) of BI 409306 and its metabolites CD 13896 and CD 14084

Time frame:
1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
Reported as:
Median · Hours
Tmax of BI 409306 and Its Metabolites
HoursExtensive Metabolisers: Ref. TreatmentExtensive Metabolisers: Test TreatmentPoor Metabolisers: Ref. TreatmentPoor Metabolisers: Test Treatment
BI 4093061.13 (0.50 to 3.00)1.75 (1.00 to 3.00)1.00 (0.50 to 4.02)2.00 (1.00 to 4.00)
CD 138961.13 (0.50 to 3.00)2.00 (1.00 to 3.00)1.25 (0.50 to 4.02)2.00 (1.50 to 4.00)
CD 140841.75 (1.00 to 4.00)2.00 (1.50 to 4.00)2.00 (1.00 to 4.02)2.50 (2.00 to 4.00)
Secondaryt1/2 of BI 409306 and Its Metabolites

Terminal half-life of the analyte in plasma (t1/2) of BI 409306 and its metabolites CD 13896 and CD 14084

Time frame:
1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
Reported as:
Geometric mean · Hours
t1/2 of BI 409306 and Its Metabolites
HoursExtensive Metabolisers: Ref. TreatmentExtensive Metabolisers: Test TreatmentPoor Metabolisers: Ref. TreatmentPoor Metabolisers: Test Treatment
BI 4093061.54 ± 16.91.73 ± 27.32.87 ± 64.12.01 ± 25.2
CD 138962.51 ± 21.42.16 ± 21.12.26 ± 20.72.17 ± 16.8
CD 140843.13 ± 22.52.62 ± 10.13.21 ± 39.92.57 ± 19.7

Adverse events

Collected over From first trial drug intake until end of washout period or end of study visit (inclusive), up to 23 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Extensive Metabolizers: Itra—0/13 (0%)3/13 (23.1%)
Extensive Metabolizers: BI 409306—0/12 (0%)1/12 (8.3%)
Extensive Metabolizers: Itra+BI 409306—0/12 (0%)3/12 (25%)
Poor Metabolizers: Itra—0/12 (0%)1/12 (8.3%)
Poor Metabolizers: BI 409306—0/12 (0%)3/12 (25%)
Poor Metabolizers: Itra+BI 409306—0/12 (0%)0/12 (0%)
Most frequent other events
Showing 10 of 14
Most frequent other events
EventExtensive Metabolizers: ItraExtensive Metabolizers: BI 409306Extensive Metabolizers: Itra+BI 409306Poor Metabolizers: ItraPoor Metabolizers: BI 409306Poor Metabolizers: Itra+BI 409306
Oropharyngeal painRespiratory, thoracic and mediastinal disorders0/130/122/120/120/120/12
Eye irritationEye disorders0/130/121/120/120/120/12
Abdominal discomfortGastrointestinal disorders0/130/121/120/120/120/12
DyspepsiaGastrointestinal disorders0/130/120/121/121/120/12
Lip dryGastrointestinal disorders0/131/120/120/120/120/12
MyalgiaMusculoskeletal and connective tissue disorders0/130/121/120/120/120/12
HeadacheNervous system disorders0/130/120/120/121/120/12
CoughRespiratory, thoracic and mediastinal disorders0/130/121/120/120/120/12
HaemoptysisRespiratory, thoracic and mediastinal disorders0/130/121/120/120/120/12
RhinorrhoeaRespiratory, thoracic and mediastinal disorders0/130/121/120/120/120/12

Baseline characteristics

Treated set which included all subjects who received at least one dose of trial medication.

Age, Continuous
Age, Continuous(Years)Extensive MetabolisersPoor MetabolisersTotal
Mean32.2 ± 8.3629.7 ± 6.5331.0 ± 7.49
Sex: Female, Male
Sex: Female, Male(Participants)Extensive MetabolisersPoor MetabolisersTotal
Female000
Male131225
08

Study locations

1 site
  • 1289.23.8201 Boehringer Ingelheim Investigational Site
    Seoul, Korea, Republic of
09

References and documents

Individual participant data

Plan to share: No — 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

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 25, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02248259
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Sep 25, 2014
Start date
Oct 8, 2014
Primary completion
Jan 7, 2015
Completion
Jan 8, 2015
Results posted
Mar 8, 2024
Last update
Apr 25, 2024

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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