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Effect of Multiple Doses of Itraconazole on the Pharmacokinetics of a Single Oral Dose of BI 1026706 in Healthy Male Subjects

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ClinicalTrials.gov Identifier: NCT02513446
Recruitment Status : Completed
First Posted : July 31, 2015
Results First Posted : March 29, 2019
Last Update Posted : March 29, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: BI 1026706
Drug: Itraconazole
Enrollment 16
Recruitment Details  
Pre-assignment Details An open-label, randomised, two-period, two-sequence crossover study with healthy male subjects
Arm/Group Title Sequence RT Sequence TR
Hide Arm/Group Description

Treatment R (BI 1026706 alone):

Oral administration of a single dose of 25 mg BI 1026706 film-coated tablets was given on Day 1.

Treatment T (itraconazole + BI 1026706):

Itraconazole (200 mg) as capsules was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).

The single dose administrations of BI 1026706 in treatments R and T were separated by a wash-out period of at least 10 days.

Treatment T (itraconazole + BI 1026706):

Itraconazole (200 mg) as capsules was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).

Treatment R (BI 1026706 alone):

Oral administration of a single dose of 25 mg BI 1026706 film-coated tablets was given on Day 1.

The single dose administrations of BI 1026706 in treatments T and R were separated by a wash-out period of at least 10 days.

Period Title: Period 1
Started 8 8
Completed 8 8
Not Completed 0 0
Period Title: Washout Period of 10 Days
Started 8 8
Completed 8 8
Not Completed 0 0
Period Title: Period 2
Started 8 8
Completed 8 8
Not Completed 0 0
Arm/Group Title Sequence RT Sequence TR Total
Hide Arm/Group Description

Treatment R (BI 1026706 alone):

Oral administration of a single dose of 25 mg BI 1026706 film-coated tablets was given on Day 1.

Treatment T (itraconazole + BI 1026706):

Itraconazole (200 mg) as capsules was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).

The single dose administrations of BI 1026706 in treatments R and T were separated by a wash-out period of at least 10 days.

Treatment T (itraconazole + BI 1026706):

Itraconazole (200 mg) as capsules was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).

Treatment R (BI 1026706 alone):

Oral administration of a single dose of 25 mg BI 1026706 film-coated tablets was given on Day 1.

The single dose administrations of BI 1026706 in treatments T and R were separated by a wash-out period of at least 10 days.

Total of all reporting groups
Overall Number of Baseline Participants 8 8 16
Hide Baseline Analysis Population Description
Treated set (TS): The TS included all subjects of the randomised set (RS), who were documented to have taken at least 1 dose of trial medication. It was used to assess safety, demographics, and other baseline characteristics as well as concomitant diseases and medications. The RS contained all entered (i.e. randomised) subjects.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 16 participants
37.9  (10.2) 33.0  (8.1) 35.4  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 16 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
8
 100.0%
8
 100.0%
16
 100.0%
1.Primary Outcome
Title Area Under the Curve of BI 1026706 From 0 to the Last Quantifiable Data Point (AUC0-tz)
Hide Description Area under the concentration-time curve of BI 1026706 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)
Time Frame -3 hours (h) before drug administration and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set (PKS) included all treated subjects that provided at least 1 primary or secondary pharmacokinetic parameter that was not excluded due to a protocol violation relevant to the evaluation of pharmacokinetics or due to pharmacokinetic non-evaluability..
Arm/Group Title Treatment R (BI 1026706 Alone) Treatment T (Itraconazole + BI 1026706)
Hide Arm/Group Description:
Oral administration of single dose of 25 mg BI 1026706 was given on Day 1.
Itraconazole (200 mg) was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).
Overall Number of Participants Analyzed 16 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
921
(47.8%)
1580
(55.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment R (BI 1026706 Alone), Treatment T (Itraconazole + BI 1026706)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Analysis of variance (ANOVA) on the logarithmic scale; Fixed effects: sequence, period and treatment; Random effects: subjects within sequences
Method of Estimation Estimation Parameter Adjusted gMean T/R ratio
Estimated Value 176.1
Confidence Interval (2-Sided) 90%
160.5 to 193.2
Estimation Comments Ratio of the treatment adjusted geometric means (gMean) of (T) versus (R).
2.Primary Outcome
Title Maximum Concentration of BI 1026706 (Cmax)
Hide Description Maximum measured concentration of BI 1026706 in plasma (Cmax)
Time Frame 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Treatment R (BI 1026706 Alone) Treatment T (Itraconazole + BI 1026706)
Hide Arm/Group Description:
Oral administration of single dose of 25 mg BI 1026706 was given on Day 1.
Itraconazole (200 mg) was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).
Overall Number of Participants Analyzed 16 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
206
(48.9%)
279
(62.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment R (BI 1026706 Alone), Treatment T (Itraconazole + BI 1026706)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Analysis of variance (ANOVA) on the logarithmic scale; Fixed effects: sequence, period and treatment; Random effects: subjects within sequences
Method of Estimation Estimation Parameter Adjusted gMean T/R ratio
Estimated Value 136.5
Confidence Interval (2-Sided) 90%
109.9 to 169.4
Estimation Comments Ratio of the treatment adjusted geometric means (gMean) of (T) versus (R).
3.Secondary Outcome
Title Area Under the Curve of BI 1026706 From 0 Extrapolated to Infinity (AUC0-inf)
Hide Description Area under the concentration-time curve of BI 1026706 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Time Frame -3 hours (h) before drug administration and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Treatment R (BI 1026706 Alone) Treatment T (Itraconazole + BI 1026706)
Hide Arm/Group Description:
Oral administration of single dose of 25 mg BI 1026706 was given on Day 1.
Itraconazole (200 mg) was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).
Overall Number of Participants Analyzed 16 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
943
(46.9%)
1600
(54.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment R (BI 1026706 Alone), Treatment T (Itraconazole + BI 1026706)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Analysis of variance (ANOVA) on the logarithmic scale; Fixed effects: sequence, period and treatment; Random effects: subjects within sequences
Method of Estimation Estimation Parameter Adjusted gMean T/R ratio
Estimated Value 174.8
Confidence Interval (2-Sided) 90%
159.1 to 192.0
Estimation Comments Ratio of the treatment adjusted geometric means (gMean) of (T) versus (R).
Time Frame From first drug administration through the residual effect period (REP) until the individual subject’s end-of-trial; Up to 14 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment R (BI 1026706 Alone) Treatment T (Itraconazole + BI 1026706) Total
Hide Arm/Group Description Oral administration of single dose of 25 mg BI 1026706 was given on Day 1. Itraconazole (200 mg) was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day). Total
All-Cause Mortality
Treatment R (BI 1026706 Alone) Treatment T (Itraconazole + BI 1026706) Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment R (BI 1026706 Alone) Treatment T (Itraconazole + BI 1026706) Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/16 (0.00%)   0/16 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment R (BI 1026706 Alone) Treatment T (Itraconazole + BI 1026706) Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/16 (18.75%)   4/16 (25.00%)   5/16 (31.25%) 
Gastrointestinal disorders       
Dyspepsia  1  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%) 
Nausea  1  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%) 
Infections and infestations       
Nasopharyngitis  1  1/16 (6.25%)  1/16 (6.25%)  2/16 (12.50%) 
Nervous system disorders       
Headache  1  1/16 (6.25%)  2/16 (12.50%)  2/16 (12.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 18.1
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02513446     History of Changes
Other Study ID Numbers: 1320.20
2015-002140-14 ( EudraCT Number: EudraCT )
First Submitted: July 30, 2015
First Posted: July 31, 2015
Results First Submitted: December 12, 2018
Results First Posted: March 29, 2019
Last Update Posted: March 29, 2019