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Trial record 25 of 50 for:    BI 201335 OR faldaprevir

Investigation of Interactions Between Faldaprevir, Itraconazole, Atorvastatin and Rosuvastatin

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ClinicalTrials.gov Identifier: NCT01795937
Recruitment Status : Completed
First Posted : February 21, 2013
Results First Posted : August 3, 2015
Last Update Posted : August 3, 2015
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Itraconazole
Drug: Atorvastatin
Drug: Faldaprevir
Drug: Rosuvastatin
Enrollment 51
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment Sequence A_B (Itraconazole Part) Treatment Sequence C_D (Statins Part) Treatment Sequence E_F (Statins Part)
Hide Arm/Group Description

The itraconazole part (interaction of steady state faldaprevir with itraconazole) of this trial was done open-label with a fixed-sequence, 2-period design; performed independently from the statins part.

Treatment A: Faldaprevir (120 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 1 (6 days in total).

Treatment B: Faldaprevir (120 mg) was given once daily from Day -3 to Day 1 (4 days). In addition, itraconazole (200 mg) was given twice daily on Day -3 and once daily from Day -2 to Day 1 (4 days in total).

Treatment A directly preceded treatment B, without an intermittent washout period.

Oral administration with 240 mL water.

The statins part (interaction of multiple dose faldaprevir with either atorvastatin or rosuvastatin) was done open-label with a fixed-sequence, 2-period design; performed independently from the itraconazole part.

Treatment C: Atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment D: Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment C preceded treatment D.

Oral administration with 240 mL water.

The statins part (interaction of multiple dose faldaprevir with either atorvastatin or rosuvastatin) was done open-label with a fixed-sequence, 2-period design; performed independently from the itraconazole part.

Treatment E: Rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment F: Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment E preceded treatment F.

Oral administration with 240 mL water.

Period Title: Overall Study
Started 18 16 17
Completed 17 15 17
Not Completed 1 1 0
Reason Not Completed
Withdrawal by Subject             1             0             0
Physician Decision             0             1             0
Arm/Group Title Treatment Sequence A_B (Itraconazole Part) Treatment Sequence C_D (Statins Part) Treatment Sequence E_F (Statins Part) Total
Hide Arm/Group Description

The itraconazole part (interaction of steady state faldaprevir with itraconazole) of this trial was done open-label with a fixed-sequence, 2-period design; performed independently from the statins part.

Treatment A: Faldaprevir (120 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 1 (6 days in total).

Treatment B: Faldaprevir (120 mg) was given once daily from Day -3 to Day 1 (4 days). In addition, itraconazole (200 mg) was given twice daily on Day -3 and once daily from Day -2 to Day 1 (4 days in total).

Treatment A directly preceded treatment B, without an intermittent washout period.

Oral administration with 240 mL water.

The statins part (interaction of multiple dose faldaprevir with either atorvastatin or rosuvastatin) was done open-label with a fixed-sequence, 2-period design; performed independently from the itraconazole part.

Treatment C: Atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment D: Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment C preceded treatment D.

Oral administration with 240 mL water.

The statins part (interaction of multiple dose faldaprevir with either atorvastatin or rosuvastatin) was done open-label with a fixed-sequence, 2-period design; performed independently from the itraconazole part.

Treatment E: Rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment F: Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment E preceded treatment F.

Oral administration with 240 mL water.

Total of all reporting groups
Overall Number of Baseline Participants 18 16 17 51
Hide Baseline Analysis Population Description
The itraconazole part of this trial was done open-label with a fixed-sequence, 2-period design (treatment seq. A_B). The statins part was done open-label with a fixed-sequence, 2-period design. Subjects in the statins part were assigned to 1 of the 2 possible treatment sequences: treatment seq. C_D or E_F. Both parts were performed independently.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 16 participants 17 participants 51 participants
39.8  (6.8) 40.0  (8.3) 38.1  (7.4) 39.3  (7.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 16 participants 17 participants 51 participants
Female
8
  44.4%
4
  25.0%
10
  58.8%
22
  43.1%
Male
10
  55.6%
12
  75.0%
7
  41.2%
29
  56.9%
1.Primary Outcome
Title AUCτ,ss (Itraconazole Part)
Hide Description Area under the concentration-time curve of the analyte in plasma at steady state over the dosing interval τ (AUCτ,ss) of faldaprevir. Outcome measure for the itraconazole part (treatment sequence A_B) of this trial. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00 h (hours) after administration of faldaprevir on Day 1 of both periods
Hide Outcome Measure Data
Hide Analysis Population Description
pharmacokinetic (PK) set of the itraconazole part of this trial. The PK set included all treated subjects of the itraconazole part that provided at least 1 observation for at least 1 primary endpoint without important protocal violations with respect to the statistical evaluation of the PK endpoints.
Arm/Group Title Faldaprevir Faldaprevir+Itraconazole
Hide Arm/Group Description:

Faldaprevir 120 mg once daily from Day -4 to Day 1 with a 120 mg twice daily loading dose on Day -5 (6 days in total).

Treatment A.

Faldaprevir 120 mg once daily from Day -3 to Day 1 + itraconazole 200 mg twice daily on Day -3 and once daily from Day -2 to Day 1 (4 days in total).

Treatment B.

Overall Number of Participants Analyzed 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
29900
(62.8%)
59500
(53.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Faldaprevir, Faldaprevir+Itraconazole
Comments Relative bioavailability comparison faldaprevir+itraconazole : faldaprevir
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 198.55
Confidence Interval (2-Sided) 90%
182.43 to 216.09
Parameter Dispersion
Type: Standard Deviation
Value: 14.2
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
2.Primary Outcome
Title Cmax,ss (Itraconazole Part)
Hide Description

Maximum measured concentration of the analyte in plasma at steady state over the dosing interval (Cmax,ss) of faldaprevir. Outcome measure for the itraconazole part (Treatment sequence A_B) of this trial.

The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00 h after administration of faldaprevir on Day 1 of both periods.
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the itraconazole part of this trial.
Arm/Group Title Faldaprevir Faldaprevir+Itraconazole
Hide Arm/Group Description:

Faldaprevir 120 mg once daily from Day -4 to Day 1 with a 120 mg twice daily loading dose on Day -5 (6 days in total).

Treatment A.

Faldaprevir 120 mg once daily from Day -3 to Day 1 + itraconazole 200 mg twice daily on Day -3 and once daily from Day -2 to Day 1 (4 days in total).

Treatment B.

Overall Number of Participants Analyzed 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
2780
(61.0%)
5030
(49.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Faldaprevir, Faldaprevir+Itraconazole
Comments Relative bioavailability comparison faldaprevir+itraconazole : faldaprevir.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 180.63
Confidence Interval (2-Sided) 90%
165.68 to 196.93
Parameter Dispersion
Type: Standard Deviation
Value: 14.5
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
3.Primary Outcome
Title AUC0-∞ of Atorvastatin (Statins Part)
Hide Description

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of atorvastatin after single dose administration. Outcome measure for the statins part of this trial, treatment sequence C_D.

The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods.
Hide Outcome Measure Data
Hide Analysis Population Description

PK set of the statins part and assigned to atorvastatin (treatment sequence C_D).

Pharmacokinetic set (PK set): all treated subjects of the statins part that provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of the pharmacokinetic endpoints.

Arm/Group Title Atorvastatin Atorvastatin+Faldaprevir
Hide Arm/Group Description:

Atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment C.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment D.

Overall Number of Participants Analyzed 16 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
13.7
(51.5%)
129.0
(43.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Atorvastatin+Faldaprevir
Comments Relative bioavailability comparison atorvastatin+faldaprevir : atorvastatin.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 946.45
Confidence Interval (2-Sided) 90%
797.61 to 1123.07
Parameter Dispersion
Type: Standard Deviation
Value: 27.3
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
4.Primary Outcome
Title Cmax of Atorvastatin (Statins Part)
Hide Description

Maximum measured concentration of the analyte in plasma of atorvastatin (Cmax). Outcome measure for the statins part of this trial, treatment sequence C_D.

The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the statins part and assigned to atorvastatin (treatment sequence C_D).
Arm/Group Title Atorvastatin Atorvastatin+Faldaprevir
Hide Arm/Group Description:

Atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment C.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment D.

Overall Number of Participants Analyzed 16 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
0.94
(35.2%)
31.10
(52.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Atorvastatin+Faldaprevir
Comments Relative bioavailability comparison atorvastatin+faldaprevir : atorvastatin.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 3372.72
Confidence Interval (2-Sided) 90%
2961.95 to 3840.47
Parameter Dispersion
Type: Standard Deviation
Value: 20.5
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
5.Primary Outcome
Title AUC0-∞ of Rosuvastatin (Statins Part)
Hide Description

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of rosuvastatin after single dose administration of rosuvastatin. Outcome measure for the statins part of this trial, treatment sequence E_F.

The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the statins part and assigned to rosuvastatin (treatment sequence E_F).
Arm/Group Title Rosuvastatin Rosuvastatin+Faldaprevir
Hide Arm/Group Description:

Rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment E.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment F.

Overall Number of Participants Analyzed 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
24.9
(49.3%)
365.0
(28.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin, Rosuvastatin+Faldaprevir
Comments Relative bioavailability comparison rosuvastatin+faldaprevir : rosuvastatin.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1466.35
Confidence Interval (2-Sided) 90%
1277.62 to 1682.95
Parameter Dispersion
Type: Standard Deviation
Value: 23.3
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
6.Primary Outcome
Title Cmax of Rosuvastatin
Hide Description

Maximum measured concentration of the analyte in plasma of rosuvastatin (Cmax). Outcome measure for the statins part of this trial, treatment sequence E_F.

The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the statins part and assigned to rosuvastatin (treatment sequence E_F).
Arm/Group Title Rosuvastatin Rosuvastatin+Faldaprevir
Hide Arm/Group Description:

Rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment E.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment F.

Overall Number of Participants Analyzed 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
2.73
(53.0%)
89.6
(33.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin, Rosuvastatin+Faldaprevir
Comments Relative bioavailability comparison rosuvastatin+faldaprevir : rosuvastatin.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 3288.70
Confidence Interval (2-Sided) 90%
2782.04 to 3887.63
Parameter Dispersion
Type: Standard Deviation
Value: 28.5
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
7.Secondary Outcome
Title AUCτ,ss of Faldaprevir (Statins Part)
Hide Description Area under the concentration-time curve of the analyte in plasma at steady state over the dosing interval τ (AUCτ,ss) of faldaprevir. Outcome measure for the statins part of this trial, treatment sequences C_D and E_F.
Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin/atorvastatin on Day 1 of the second periods of each treatment sequence.
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the statins part.
Arm/Group Title Atorvastatin+Faldaprevir Rosuvastatin+Faldaprevir
Hide Arm/Group Description:

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment D.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment F.

Overall Number of Participants Analyzed 15 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
145000
(34.3%)
136000
(43.9%)
8.Secondary Outcome
Title Cmax,ss of Faldaprevir (Statins Part)
Hide Description Maximum measured concentration of the analyte in plasma at steady state over the dosing interval (Cmax,ss) of faldaprevir. Outcome measure for the statins part of this trial, treatment sequences C_D and E_F.
Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin/atorvastatin on Day 1 of the second periods of each treatment sequence.
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the statins part.
Arm/Group Title Atorvastatin+Faldaprevir Rosuvastatin+Faldaprevir
Hide Arm/Group Description:

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment D.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment F.

Overall Number of Participants Analyzed 15 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
12900
(27.8%)
12200
(36.8%)
9.Secondary Outcome
Title AUC0-tz of Atorvastatin
Hide Description

Area under the plasma concentration-time curve of the analyte over the time interval from 0 to the time tz of the last measurable concentration (AUC0-tz) of atorvastatin. Outcome measure for the statins part of this trial, treatment sequence C_D.

The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the statins part and assigned to atorvastatin (treatment sequence C_D).
Arm/Group Title Atorvastatin Atorvastatin+Faldaprevir
Hide Arm/Group Description:

Atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment C.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.

Treatment D.

Overall Number of Participants Analyzed 16 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
9.5
(40.2%)
129.6
(44.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Atorvastatin+Faldaprevir
Comments Relative bioavailability comparison atorvastatin+faldaprevir : atorvastatin.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1358.91
Confidence Interval (2-Sided) 90%
1224.32 to 1508.29
Parameter Dispersion
Type: Standard Deviation
Value: 16.4
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
10.Secondary Outcome
Title AUC0-tz of Rosuvastatin
Hide Description

Area under the plasma concentration-time curve of the analyte over the time interval from 0 to the time tz of the last measurable concentration (AUC0-tz) of rosuvastatin. Outcome measure for the statins part of this trial, treatment sequence E_F.

The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods
Hide Outcome Measure Data
Hide Analysis Population Description
PK set of the statins part and assigned to rosuvastatin (treatment sequence E_F).
Arm/Group Title Rosuvastatin Rosuvastatin+Faldaprevir
Hide Arm/Group Description:

Rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment E.

Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.

Treatment F.

Overall Number of Participants Analyzed 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
21.5
(48.0%)
361.0
(28.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rosuvastatin, Rosuvastatin+Faldaprevir
Comments Relative bioavailability comparison rosuvastatin+faldaprevir : rosuvastatin.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Investigation of relative bioavailability (no formal testing).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA with fixed effect for treatment and random effect for subject.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1678.23
Confidence Interval (2-Sided) 90%
1468.52 to 1917.89
Parameter Dispersion
Type: Standard Deviation
Value: 22.6
Estimation Comments The standard deviation is actually the geometric coefficient of variation.
Time Frame Adverse events were to be recorded from screening until the end-of-trial examination. Itraconazole part: up to 25 days. Statins part: up to 33 days.
Adverse Event Reporting Description Adverse events were recorded throughout the clinical trial, but were specifically asked for at prespecified time points and additionally whenever the investigator deemed necessary. Subjects were asked to spontaneously report any adverse events as well as the time of onset, end, and intensity.
 
Arm/Group Title Faldaprevir (Itraconazole Part) Faldaprevir+Itraconazole (Itraconazole Part) Atorvastatin (Statins Part) Rosuvastatin (Statins Part) Faldaprevir (Statins Part) Faldaprevir + Atorvastatin (Statins Part) Faldaprevir + Rosuvastatin (Statins Part)
Hide Arm/Group Description

Faldaprevir: 120 mg once daily with a 120 mg twice daily loading dose on Day -5.

Treatment A.

Faldaprevir: 120 mg once daily. Itraconazole: 200 mg once daily with a 200 mg twice daily loading dose on Day -3.

Treatment B.

Atorvastatin: 10 mg was given as a single dose on Day 1.

Treatment C.

From the time of the single dose atorvastatin administration in treatment C until the time of the first faldaprevir administration in treatment D or until 1 day after the trial completion date of the respective subject.

Rosuvastatin: 10 mg was given as a single dose on Day 1.

Treatment E.

From the time of the single dose rosuvastatin administration in treatment E until the time of the first faldaprevir administration in treatment F or until 1 day after the trial completion date.

From the time of the first faldaprevir administration in treatment D or F until the combined administration of faldaprevir with atorvastatin or rosuvastatin in treatment D or F, respectively, or until 1 day after the trial completion date.

Faldaprevir: 240 mg was given twice daily on Day -5 and once daily from Day -4 to Day 2. Atorvastatin: 10 mg was given as a single dose on Day 1.

Treatment D.

From the time of the combined administration of faldaprevir with atorvastatin in treatment D until 1 day after the trial completion date.

Faldaprevir: 240 mg was given twice daily on Day -5 and once daily from Day -4 to Day 2. Rosuvastatin: 10 mg was given as a single dose on Day 1.

Treatment F.

From the time of the combined administration of faldaprevir with rosuvastatin in treatment F until 1 day after the trial completion date.

All-Cause Mortality
Faldaprevir (Itraconazole Part) Faldaprevir+Itraconazole (Itraconazole Part) Atorvastatin (Statins Part) Rosuvastatin (Statins Part) Faldaprevir (Statins Part) Faldaprevir + Atorvastatin (Statins Part) Faldaprevir + Rosuvastatin (Statins Part)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Faldaprevir (Itraconazole Part) Faldaprevir+Itraconazole (Itraconazole Part) Atorvastatin (Statins Part) Rosuvastatin (Statins Part) Faldaprevir (Statins Part) Faldaprevir + Atorvastatin (Statins Part) Faldaprevir + Rosuvastatin (Statins Part)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/17 (0.00%)   0/16 (0.00%)   0/17 (0.00%)   0/32 (0.00%)   0/15 (0.00%)   0/17 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Faldaprevir (Itraconazole Part) Faldaprevir+Itraconazole (Itraconazole Part) Atorvastatin (Statins Part) Rosuvastatin (Statins Part) Faldaprevir (Statins Part) Faldaprevir + Atorvastatin (Statins Part) Faldaprevir + Rosuvastatin (Statins Part)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/18 (72.22%)   3/17 (17.65%)   5/16 (31.25%)   4/17 (23.53%)   23/32 (71.88%)   8/15 (53.33%)   9/17 (52.94%) 
Cardiac disorders               
Palpitations  1  0/18 (0.00%)  1/17 (5.88%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Eye disorders               
Ocular icterus  1  1/18 (5.56%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  4/32 (12.50%)  5/15 (33.33%)  3/17 (17.65%) 
Gastrointestinal disorders               
Nausea  1  2/18 (11.11%)  1/17 (5.88%)  0/16 (0.00%)  0/17 (0.00%)  13/32 (40.63%)  0/15 (0.00%)  2/17 (11.76%) 
Dry mouth  1  0/18 (0.00%)  1/17 (5.88%)  0/16 (0.00%)  1/17 (5.88%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Abdominal pain  1  1/18 (5.56%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Diarrhoea  1  1/18 (5.56%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  6/32 (18.75%)  0/15 (0.00%)  0/17 (0.00%) 
Flatulence  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  3/32 (9.38%)  0/15 (0.00%)  0/17 (0.00%) 
Dyspepsia  1  0/18 (0.00%)  0/17 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  2/32 (6.25%)  1/15 (6.67%)  0/17 (0.00%) 
Vomiting  1  1/18 (5.56%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
General disorders               
Fatigue  1  6/18 (33.33%)  0/17 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  5/32 (15.63%)  0/15 (0.00%)  0/17 (0.00%) 
Thirst  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Hepatobiliary disorders               
Jaundice  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  1/15 (6.67%)  0/17 (0.00%) 
Immune system disorders               
Seasonal allergy  1  0/18 (0.00%)  0/17 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Infections and infestations               
Nasopharyngitis  1  2/18 (11.11%)  0/17 (0.00%)  1/16 (6.25%)  1/17 (5.88%)  1/32 (3.13%)  0/15 (0.00%)  0/17 (0.00%) 
Rhinitis  1  0/18 (0.00%)  0/17 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Sinusitis  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Injury, poisoning and procedural complications               
Sunburn  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  2/15 (13.33%)  0/17 (0.00%) 
Hand fracture  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders               
Muscle spasms  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  1/15 (6.67%)  0/17 (0.00%) 
Nervous system disorders               
Headache  1  10/18 (55.56%)  0/17 (0.00%)  0/16 (0.00%)  2/17 (11.76%)  3/32 (9.38%)  2/15 (13.33%)  3/17 (17.65%) 
Dizziness  1  2/18 (11.11%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  2/32 (6.25%)  1/15 (6.67%)  0/17 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Rhinitis allergic  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  1/15 (6.67%)  0/17 (0.00%) 
Oropharyngeal pain  1  0/18 (0.00%)  0/17 (0.00%)  1/16 (6.25%)  1/17 (5.88%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Skin and subcutaneous tissue disorders               
Dry skin  1  0/18 (0.00%)  1/17 (5.88%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  0/17 (0.00%) 
Pruritus  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  2/15 (13.33%)  0/17 (0.00%) 
Erythema  1  0/18 (0.00%)  0/17 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/32 (0.00%)  1/15 (6.67%)  0/17 (0.00%) 
Vascular disorders               
Haematoma  1  0/18 (0.00%)  0/17 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/32 (0.00%)  0/15 (0.00%)  1/17 (5.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 16.0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01795937     History of Changes
Other Study ID Numbers: 1220.61
2012-005518-20 ( EudraCT Number: EudraCT )
First Submitted: February 20, 2013
First Posted: February 21, 2013
Results First Submitted: July 3, 2015
Results First Posted: August 3, 2015
Last Update Posted: August 3, 2015