Relative Bioavailability of BI 201335 Capsule Versus Three Different Oral Solutions
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT01764945
Collaborator
(none)
56
1
2
1.9
28.9
Study Details
Study Description
Brief Summary
The objective of the current study is to investigate the relative bioavailability of two different doses of BI 201335, administered as soft gelatine capsule in comparison to the equivalent doses of three different oral solution per dose of BI 201335.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
56 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Relative Bioavailability of BI 201335 (Capsule) Compared to Three Different Oral Solutions of BI 201335 Following Oral Administration in Healthy Male and Female Volunteers (an Open-label, Randomised, Single-dose, Four-way Crossover Study)
Study Start Date
:
Jan 1, 2013
Actual Primary Completion Date
:
Mar 1, 2013
Actual Study Completion Date
:
Mar 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 BI 201335 low dose |
Drug: BI 201335 (Reference)
soft gelatine capsule, oral administration
Drug: BI 201335 (Test)
oral solution 3
Drug: BI 201335 (Test)
oral solution 2
Drug: BI 201335 (Test)
oral solution 1
|
| Experimental: 2 BI 201335 high dose |
Drug: BI 201335 (Test)
oral solution 3
Drug: BI 201335 (Reference)
soft gelatine capsule, oral administration
Drug: BI 201335 (Test)
oral solution 1
Drug: BI 201335 (Test)
oral solution 2
|
Outcome Measures
Primary Outcome Measures
- AUC0-∞ [-1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h (hours) after administration of faldaprevir on Day 1.]
Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 extrapolated to infinity. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
- Cmax [-1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1.]
Maximum measured concentration of the analyte (faldaprevir) in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
- AUC0-tz [-1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1.]
Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 to the time of the last quantifiable data point. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion criteria:
- Healthy male and female subjects
Exclusion criteria:
Any relevant deviation from healthy conditions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1220.46.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01764945
Other Study ID Numbers:
- 1220.46
- 2012-000687-22
First Posted:
Jan 10, 2013
Last Update Posted:
Jul 31, 2015
Last Verified:
Jul 1, 2015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 40mg Faldaprevir: Sequence Group ADBC | 40mg Faldaprevir: Sequence Group BACD | 40mg Faldaprevir: Sequence Group CBDA | 40mg Faldaprevir: Sequence Group DCAB | 120mg Faldaprevir: Sequence Group EHFG | 120mg Faldaprevir: Sequence Group FEGH | 120mg Faldaprevir: Sequence Group GFHE | 120mg Faldaprevir: Sequence Group HGEF |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is ADBC with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is BACD with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is CBDA with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is DCAB with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is EHFG with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is FEGH with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is GFHE with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is HGEF with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). |
| Period Title: Overall Study | ||||||||
| STARTED | 5 | 5 | 5 | 5 | 10 | 8 | 9 | 9 |
| COMPLETED | 5 | 4 | 5 | 5 | 10 | 8 | 8 | 9 |
| NOT COMPLETED | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | 40mg Faldaprevir: Sequence Group ADBC | 40mg Faldaprevir: Sequence Group BACD | 40mg Faldaprevir: Sequence Group CBDA | 40mg Faldaprevir: Sequence Group DCAB | 120mg Faldaprevir: Sequence Group EHFG | 120mg Faldaprevir: Sequence Group FEGH | 120mg Faldaprevir: Sequence Group GFHE | 120mg Faldaprevir: Sequence Group HGEF | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is ADBC with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is BACD with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is CBDA with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D). The order of treatment administration in this sequence group is DCAB with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is EHFG with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is FEGH with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is GFHE with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H). The order of treatment administration in this sequence group is HGEF with washout phases of at least 14 days between drug administrations. Oral administration (under fed conditions, i.e. following a high-fat breakfast). | Total of all reporting groups |
| Overall Participants | 5 | 5 | 5 | 5 | 10 | 8 | 9 | 9 | 56 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [years] |
41.2
(5.3)
|
39.8
(5.1)
|
38.0
(10.2)
|
44.4
(4.2)
|
33.9
(9.7)
|
38.6
(9.6)
|
39.4
(8.1)
|
34.9
(9.5)
|
38.1
(8.5)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
2
40%
|
3
60%
|
2
40%
|
2
40%
|
5
50%
|
4
50%
|
7
77.8%
|
3
33.3%
|
28
50%
|
| Male |
3
60%
|
2
40%
|
3
60%
|
3
60%
|
5
50%
|
4
50%
|
2
22.2%
|
6
66.7%
|
28
50%
|
Outcome Measures
| Title | AUC0-∞ |
|---|---|
| Description | Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 extrapolated to infinity. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Time Frame | -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h (hours) after administration of faldaprevir on Day 1. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PK set) includes all subjects who provided evaluable data for at least 1 evaluable observation for a PK endpoint in at least 1 treatment period. |
| Arm/Group Title | 40mg Faldaprevir: Treatment A | 40mg Faldaprevir: Treatment B | 40mg Faldaprevir: Treatment C | 40mg Faldaprevir: Treatment D | 120mg Faldaprevir: Treatment E | 120mg Faldaprevir: Treatment F | 120mg Faldaprevir: Treatment G | 120mg Faldaprevir: Treatment H |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 40 mg faldaprevir soft gelatine capsule (reference). | 40 mg faldaprevir oral solution 1 | 40 mg faldaprevir oral solution 2 | 40 mg faldaprevir oral solution 3 | 120 mg faldaprevir soft gelatine capsule (reference). | 120 mg faldaprevir oral solution 1 | 120 mg faldaprevir oral solution 2 | 120 mg faldaprevir oral solution 3 |
| Measure Participants | 19 | 19 | 20 | 18 | 35 | 35 | 36 | 35 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3960
(32.3)
|
3400
(28.5)
|
3350
(28.4)
|
3420
(30.4)
|
15000
(34.5)
|
13900
(38.8)
|
14500
(38.3)
|
14100
(36.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment B |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment B : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 82.58 | |
| Confidence Interval |
(2-Sided) 90% 73.69 to 92.54 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 19.7 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment C |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment C : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 83.34 | |
| Confidence Interval |
(2-Sided) 90% 73.65 to 94.30 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 22.2 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment D |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment D : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 83.92 | |
| Confidence Interval |
(2-Sided) 90% 74.69 to 94.28 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 19.6 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment F |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment F : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 92.90 | |
| Confidence Interval |
(2-Sided) 90% 88.94 to 97.04 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 10.5 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment G |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment G : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 96.37 | |
| Confidence Interval |
(2-Sided) 90% 91.55 to 101.43 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 12.7 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment H |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment H : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 94.44 | |
| Confidence Interval |
(2-Sided) 90% 89.88 to 99.24 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 12.0 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
| Title | Cmax |
|---|---|
| Description | Maximum measured concentration of the analyte (faldaprevir) in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Time Frame | -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set. |
| Arm/Group Title | 40mg Faldaprevir: Treatment A | 40mg Faldaprevir: Treatment B | 40mg Faldaprevir: Treatment C | 40mg Faldaprevir: Treatment D | 120mg Faldaprevir: Treatment E | 120mg Faldaprevir: Treatment F | 120mg Faldaprevir: Treatment G | 120mg Faldaprevir: Treatment H |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 40 mg faldaprevir soft gelatine capsule (reference). | 40 mg faldaprevir oral solution 1 | 40 mg faldaprevir oral solution 2 | 40 mg faldaprevir oral solution 3 | 120 mg faldaprevir soft gelatine capsule (reference). | 120 mg faldaprevir oral solution 1 | 120 mg faldaprevir oral solution 2 | 120 mg faldaprevir oral solution 3 |
| Measure Participants | 19 | 19 | 20 | 18 | 35 | 35 | 36 | 35 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
86.4
(36.0)
|
65.4
(39.0)
|
64.0
(40.4)
|
69.7
(28.1)
|
625.0
(47.3)
|
481.0
(47.1)
|
488.0
(52.1)
|
485.0
(48.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment B |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment B : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 74.07 | |
| Confidence Interval |
(2-Sided) 90% 65.44 to 83.83 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 21.5 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment C |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment C : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 73.23 | |
| Confidence Interval |
(2-Sided) 90% 63.33 to 84.68 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 26.2 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment D |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment D : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 78.76 | |
| Confidence Interval |
(2-Sided) 90% 68.94 to 89.99 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 22.7 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment F |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment F : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 78.30 | |
| Confidence Interval |
(2-Sided) 90% 71.42 to 85.84 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 22.5 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment G |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment G : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 78.43 | |
| Confidence Interval |
(2-Sided) 90% 69.54 to 88.46 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 30.4 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment H |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment H : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 78.09 | |
| Confidence Interval |
(2-Sided) 90% 69.35 to 87.94 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 29.4 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
| Title | AUC0-tz |
|---|---|
| Description | Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 to the time of the last quantifiable data point. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Time Frame | -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set. |
| Arm/Group Title | 40mg Faldaprevir: Treatment A | 40mg Faldaprevir: Treatment B | 40mg Faldaprevir: Treatment C | 40mg Faldaprevir: Treatment D | 120mg Faldaprevir: Treatment E | 120mg Faldaprevir: Treatment F | 120mg Faldaprevir: Treatment G | 120mg Faldaprevir: Treatment H |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 40 mg faldaprevir soft gelatine capsule (reference). | 40 mg faldaprevir oral solution 1 | 40 mg faldaprevir oral solution 2 | 40 mg faldaprevir oral solution 3 | 120 mg faldaprevir soft gelatine capsule (reference). | 120 mg faldaprevir oral solution 1 | 120 mg faldaprevir oral solution 2 | 120 mg faldaprevir oral solution 3 |
| Measure Participants | 19 | 19 | 20 | 18 | 35 | 35 | 36 | 35 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3020
(29.4)
|
2600
(32.9)
|
2520
(38.3)
|
2550
(34.3)
|
14200
(35.2)
|
12900
(39.4)
|
13400
(38.0)
|
13100
(37.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment B |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment B : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 82.02 | |
| Confidence Interval |
(2-Sided) 90% 75.98 to 88.55 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 13.1 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment C |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment C : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 80.93 | |
| Confidence Interval |
(2-Sided) 90% 74.58 to 87.83 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 14.5 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 40mg Faldaprevir: Treatment A, 40mg Faldaprevir: Treatment D |
|---|---|---|
| Comments | relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment D : treatment A). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 79.60 | |
| Confidence Interval |
(2-Sided) 90% 74.84 to 84.67 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 10.2 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment F |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment F : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 91.59 | |
| Confidence Interval |
(2-Sided) 90% 87.53 to 95.84 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 11.0 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment G |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment G : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 94.38 | |
| Confidence Interval |
(2-Sided) 90% 89.76 to 99.24 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 12.4 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 120mg Faldaprevir: Treatment E, 120mg Faldaprevir: Treatment H |
|---|---|---|
| Comments | relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution. (treatment H : treatment E). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | investigation of relative bioavailability (no formal testing). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 92.91 | |
| Confidence Interval |
(2-Sided) 90% 88.42 to 97.63 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 12.0 |
|
| Estimation Comments | the standard deviation is actually the geometric coefficient of variation. | |
Adverse Events
| Time Frame | AEs and concomitant medication will be evaluated continuously from first drug administration until the end-of-study examination (up to 5 weeks). AEs persisting after trial completion must be followed up, until they have normalised. | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Subjects were required to report spontaneously any AEs throughout the clinical trial. In addition, each volunteer was assessed regularly by the medical staff throughout the clinical trial as well as at the end of observation and whenever necessary as deemed by the investigator. | |||||||||||||||
| Arm/Group Title | 40mg Faldaprevir: Treatment A | 40mg Faldaprevir: Treatment B | 40mg Faldaprevir: Treatment C | 40mg Faldaprevir: Treatment D | 120mg Faldaprevir: Treatment E | 120mg Faldaprevir: Treatment F | 120mg Faldaprevir: Treatment G | 120mg Faldaprevir: Treatment H | ||||||||
| Arm/Group Description | 40 mg faldaprevir soft gelatine capsule (reference). | 40 mg faldaprevir oral solution 1. | 40 mg faldaprevir oral solution 2. | 40 mg faldaprevir oral solution 3. | 120 mg faldaprevir soft gelatine capsule (reference). | 120 mg faldaprevir oral solution 1. | 120 mg faldaprevir oral solution 2. | 120 mg faldaprevir oral solution 3. | ||||||||
All Cause Mortality |
||||||||||||||||
| 40mg Faldaprevir: Treatment A | 40mg Faldaprevir: Treatment B | 40mg Faldaprevir: Treatment C | 40mg Faldaprevir: Treatment D | 120mg Faldaprevir: Treatment E | 120mg Faldaprevir: Treatment F | 120mg Faldaprevir: Treatment G | 120mg Faldaprevir: Treatment H | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| 40mg Faldaprevir: Treatment A | 40mg Faldaprevir: Treatment B | 40mg Faldaprevir: Treatment C | 40mg Faldaprevir: Treatment D | 120mg Faldaprevir: Treatment E | 120mg Faldaprevir: Treatment F | 120mg Faldaprevir: Treatment G | 120mg Faldaprevir: Treatment H | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/19 (0%) | 0/20 (0%) | 0/20 (0%) | 0/19 (0%) | 0/35 (0%) | 0/36 (0%) | 0/36 (0%) | 0/35 (0%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| 40mg Faldaprevir: Treatment A | 40mg Faldaprevir: Treatment B | 40mg Faldaprevir: Treatment C | 40mg Faldaprevir: Treatment D | 120mg Faldaprevir: Treatment E | 120mg Faldaprevir: Treatment F | 120mg Faldaprevir: Treatment G | 120mg Faldaprevir: Treatment H | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/19 (15.8%) | 2/20 (10%) | 8/20 (40%) | 6/19 (31.6%) | 6/35 (17.1%) | 5/36 (13.9%) | 7/36 (19.4%) | 8/35 (22.9%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Nausea | 0/19 (0%) | 0/20 (0%) | 1/20 (5%) | 2/19 (10.5%) | 1/35 (2.9%) | 1/36 (2.8%) | 0/36 (0%) | 0/35 (0%) | ||||||||
| Abdominal pain | 0/19 (0%) | 0/20 (0%) | 0/20 (0%) | 1/19 (5.3%) | 0/35 (0%) | 0/36 (0%) | 0/36 (0%) | 0/35 (0%) | ||||||||
| Diarrhoea | 1/19 (5.3%) | 0/20 (0%) | 0/20 (0%) | 1/19 (5.3%) | 1/35 (2.9%) | 0/36 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||||||
| Vomiting | 0/19 (0%) | 0/20 (0%) | 0/20 (0%) | 1/19 (5.3%) | 1/35 (2.9%) | 1/36 (2.8%) | 0/36 (0%) | 0/35 (0%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Oral herpes | 0/19 (0%) | 0/20 (0%) | 2/20 (10%) | 0/19 (0%) | 0/35 (0%) | 0/36 (0%) | 2/36 (5.6%) | 1/35 (2.9%) | ||||||||
| Influenza | 1/19 (5.3%) | 0/20 (0%) | 1/20 (5%) | 0/19 (0%) | 0/35 (0%) | 1/36 (2.8%) | 0/36 (0%) | 1/35 (2.9%) | ||||||||
| Rhinitis | 0/19 (0%) | 1/20 (5%) | 1/20 (5%) | 1/19 (5.3%) | 1/35 (2.9%) | 0/36 (0%) | 3/36 (8.3%) | 0/35 (0%) | ||||||||
| Nasopharyngitis | 0/19 (0%) | 1/20 (5%) | 1/20 (5%) | 0/19 (0%) | 4/35 (11.4%) | 0/36 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Headache | 1/19 (5.3%) | 0/20 (0%) | 4/20 (20%) | 1/19 (5.3%) | 1/35 (2.9%) | 3/36 (8.3%) | 4/36 (11.1%) | 4/35 (11.4%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Urine odour abnormal | 0/19 (0%) | 0/20 (0%) | 0/20 (0%) | 1/19 (5.3%) | 0/35 (0%) | 0/36 (0%) | 0/36 (0%) | 0/35 (0%) | ||||||||
| Reproductive system and breast disorders | ||||||||||||||||
| Dysmenorrhoea | 0/19 (0%) | 0/20 (0%) | 0/20 (0%) | 1/19 (5.3%) | 0/35 (0%) | 0/36 (0%) | 0/36 (0%) | 0/35 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Cough | 0/19 (0%) | 0/20 (0%) | 1/20 (5%) | 2/19 (10.5%) | 0/35 (0%) | 0/36 (0%) | 0/36 (0%) | 0/35 (0%) | ||||||||
| Oropharyngeal pain | 0/19 (0%) | 0/20 (0%) | 0/20 (0%) | 1/19 (5.3%) | 1/35 (2.9%) | 0/36 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
| Name/Title | Boehringer Ingelheim Call Center |
|---|---|
| Organization | Boehringer Ingelheim |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01764945
Other Study ID Numbers:
- 1220.46
- 2012-000687-22
First Posted:
Jan 10, 2013
Last Update Posted:
Jul 31, 2015
Last Verified:
Jul 1, 2015