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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002498-23 | EudraCT Number | EudraCT |
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To investigate the relative bioavailability of dabigatran etexilate as pellets on food and of dabigatran etexilate as granules resolved in reconstitution solution, each with dabigatran etexilate as capsule following oral administration. To evaluate acceptability and palatability of Pellets sprinkled on food and Oral Liquid Formulation
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test 1 (Treatment A) | Experimental | multiple dose of dabigatran |
|
| Test 2 (Treatment B) | Experimental | multiple dose of dabigatran |
|
| Reference | Experimental | multiple dose of dabigatran |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabigatran etexilate | Drug | Pellets (multiple dose of dabigatran) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran. | Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran. | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
| Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran. | Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran. | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran. | Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran. | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
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Inclusion criteria:
Exclusion criteria:
Any finding in the medical examination (including Blood Pressure, Pulse Rate or electrocardiogram) deviating from normal and judged clinically relevant by the investigator.
Repeated measurement of systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg
Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
Any evidence of a concomitant disease judged clinically relevant by the investigator
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug
Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders
Subjects who in the investigator's judgement are perceived as having an increased risk of bleeding, for example because of:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1160.194.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
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| ID | Title | Description |
|---|---|---|
| FG000 | T1-T2-R | T1: pellets on food; T2: granules for reconstitution into solution; R: hard capsule. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
| FG001 | T1-R-T2 | T1: pellets on food; R: hard capsule; T2: granules for reconstitution into solution. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
| FG002 | T2-T1-R | T2: granules for reconstitution into solution; T1: pellets on food; R: hard capsule. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
| FG003 | T2-R-T1 | T2: granules for reconstitution into solution; R: hard capsule; T1: pellets on food. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
| FG004 | R-T1-T2 | R: hard capsule; T1: pellets on food; T2: granules for reconstitution into solution. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
| FG005 | R-T2-T1 | R: hard capsule; T2: granules for reconstitution into solution; T1: pellets on food. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The evaluation of demographic and baseline characteristics were performed on the treated set which included all subjects who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall | A randomised, open-label, 3-way crossover, multiple dose trial consisting of 3 identical treatment periods of 3 days. Study drug (150 mg dabigatran etexilate) was administrated twice daily on Day 1 and Day 2 and once on Day 3. The dosage forms used were: hard capsule, granules resolved in reconstitution solution and pellets on food. Treatment periods were separated by a washout phase of at least 5 days between last drug administration of one treatment and the first drug administration of the next treatment. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran. | Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran. | Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng∙h/mL | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
|
First dose of study drug date/time until the end-of-trial examination (last per protocol visit)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | T1 (Treatment A) | multiple dose of dabigatran (Pellets). The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MEDDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
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| Dabigatran etexilate |
| Drug |
Granules resolved in reconstitution solution (multiple dose of dabigatran) |
|
| Dabigatran etexilate | Drug | Hard capsule (multiple dose of dabigatran) |
|
| Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran. | Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran. | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
| Acceptability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question. | Acceptability question: "Would you accept to take this medication for chronic use?" with 3 possible answers: Yes - No - I am not sure. | once on day 3 (48 hours after first dose) |
| Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question. | Palatability question: "How do you rank the taste?" with 5 possible answers: Very good - Good - Fair - Acceptable - Not acceptable. | once on day 3 (48 hours after first dose) |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| OG001 | T2 (Treatment B) | multiple dose of dabigatran (Granules resolved in reconstitution solution) The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
| OG002 | R (Reference) | multiple dose of dabigatran (Hard capsule) The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. |
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| Primary | Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran. | Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran. | Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
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| Secondary | Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran. | Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran. | Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
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| Secondary | Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran. | Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran. | Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration |
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| Secondary | Acceptability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question. | Acceptability question: "Would you accept to take this medication for chronic use?" with 3 possible answers: Yes - No - I am not sure. | Treated set including all subjects that provided at least 1 observation for at least 1 of the questions for at least 1 of the test products. | Posted | Number | participants | once on day 3 (48 hours after first dose) |
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| Secondary | Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question. | Palatability question: "How do you rank the taste?" with 5 possible answers: Very good - Good - Fair - Acceptable - Not acceptable. | Treated set including all subjects that provided at least 1 observation for at least 1 of the questions for at least 1 of the test products. | Posted | Number | participants | once on day 3 (48 hours after first dose) |
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| 0 |
| 54 |
| 2 |
| 54 |
| EG001 | T2 (Treatment B) | multiple dose of dabigatran (Granules resolved in reconstitution solution) The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. | 0 | 54 | 3 | 54 |
| EG002 | R (Reference) | multiple dose of dabigatran (Hard capsule) The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water. | 0 | 54 | 1 | 54 |
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| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Analysis of variance (ANOVA) on the logarithmic scale was used including effects for 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. CIs were calculated based on the residual error from ANOVA. | gMean Ratio T2/R (%) | 141.06 | Standard Deviation | 31.5 | 2-Sided | 90 | 127.644 | 155.876 | The standard deviation is actually the intra-individual geometric coefficient of variation (gCV). | Yes | Non-Inferiority or Equivalence | The sample size determination was not based on a power calculation, but to assure a precise estimation of the relative bioavailability. For this 3-way crossover trial, a precision (defined by ratio of upper CI limit to adjusted GMR) of at most 1.17 had been considered necessary and sufficient by the project team. |
| Analysis of variance (ANOVA) on the logarithmic scale was used including effects for 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. CIs were calculated based on the residual error from ANOVA. | gMean Ratio T2/R (%) | 132.00 | Standard Deviation | 28.0 | 2-Sided | 90 | 120.714 | 144.342 | The standard deviation is actually the intra-individual geometric coefficient of variation (gCV). | Yes | Non-Inferiority or Equivalence | The sample size determination was not based on a power calculation, but to assure a precise estimation of the relative bioavailability. For this 3-way crossover trial, a precision (defined by ratio of upper CI limit to adjusted GMR) of at most 1.17 had been considered necessary and sufficient by the project team. |
| Analysis of variance (ANOVA) on the logarithmic scale was used including effects for 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. CIs were calculated based on the residual error from ANOVA. | gMean Ratio T2/R (%) | 144.80 | Standard Deviation | 32.0 | 2-Sided | 90 | 130.853 | 160.242 | The standard deviation is actually the intra-individual geometric coefficient of variation (gCV). | Yes | Non-Inferiority or Equivalence | The sample size determination was not based on a power calculation, but to assure a precise estimation of the relative bioavailability. For this 3-way crossover trial, a precision (defined by ratio of upper CI limit to adjusted GMR) of at most 1.17 had been considered necessary and sufficient by the project team. |
| I am not sure |
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| Fair |
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| Acceptable |
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| Not acceptable |
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