Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate effect of faldaprevir on steady state pharmacokinetics of raltegravir. The assessment of safety and tolerability will be an additional objective of this trial.
Interventions
DRUGRaltegravir
low dose oral administration
DRUGFaldaprevir
medium dose oral administration
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1\. healthy male subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC( Tau,ss) | 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132 hours after RAL and FDV administration | AUC tau,ss (area under the concentration-time curve of the Raltegravir in plasma at steady state over the uniform dosing interval tau) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of AUC tau,ss and their 2-sided 90% confidence intervals (CI) were calculated. The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for 'subject' and 'treatment'. RAL: Raltegravir , FDV: Faldaprevir |
| Cmax ,ss | 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132hours after RAL and FDV administration | C max,ss (maximum measured concentration of the Raltegravir in plasma at steady state) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of Cmax,ss and their 2-sided 90% confidence intervals (CI) were calculated. The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for 'subject' and 'treatment'. RAL: Raltegravir , FDV: Faldaprevir |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Total number of patients randomised and treated in the study.This was a open label trial with two periods in a fixed sequence. All subjects were to receive the following 2 treatments, A\]Raltegravir B\]Raltegravir+Faldaprevir The two treatments were separated by washout period of at least 7 days. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period 1: Raltegravir | Not treated | 1 |
| Washout Period of at Least 7 Days | Consent withdrawn | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 40.8 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 13 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 |
Outcome results
Primary
AUC( Tau,ss)
AUC tau,ss (area under the concentration-time curve of the Raltegravir in plasma at steady state over the uniform dosing interval tau) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of AUC tau,ss and their 2-sided 90% confidence intervals (CI) were calculated. The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for 'subject' and 'treatment'. RAL: Raltegravir , FDV: Faldaprevir
Time frame: 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132 hours after RAL and FDV administration
Population: Pharmacokinetic(PK) set:Subjects who received atleast 1 dose of study medication and who provided at least 1 observation for at least 1 PK endpoint without any important protocol violations relevant to the evaluation of relative bioavailability and did not experience emesis at or before 2 times median tmax on the pk study days of both trial periods
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Raltegravir | AUC( Tau,ss) | 4070 ng*h/mL | Geometric Coefficient of Variation 92.9 |
| Raltegravir + Faldaprevir | AUC( Tau,ss) | 11100 ng*h/mL | Geometric Coefficient of Variation 78.7 |
Comparison: Ratio Raltegravir plus Faldaprevir and Raltegravir for the category Raltegravirp-value: 0.999995% CI: [199.69, 370.66]ANOVA
Primary
Cmax ,ss
C max,ss (maximum measured concentration of the Raltegravir in plasma at steady state) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of Cmax,ss and their 2-sided 90% confidence intervals (CI) were calculated. The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for 'subject' and 'treatment'. RAL: Raltegravir , FDV: Faldaprevir
Time frame: 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132hours after RAL and FDV administration
Population: Pharmacokinetic(PK) set:Subjects who received atleast 1 dose of study medication and who provided at least 1 observation for at least 1 PK endpoint without any important protocol violations relevant to the evaluation of relative bioavailability and did not experience emesis at or before 2 times median tmax on the pk study days of both trial periods
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Raltegravir | Cmax ,ss | 1300 ng/mL | Geometric Coefficient of Variation 115 |
| Raltegravir + Faldaprevir | Cmax ,ss | 3220 ng/mL | Geometric Coefficient of Variation 108 |
Comparison: Ratio Raltegravir plus Faldaprevir and Raltegravir for the category Raltegravirp-value: 0.997395% CI: [168.46, 358.404]ANOVA