Trial Outcomes & Findings for Investigation of Ritonavir Effects on Afatinib Exposure in Healthy Subjects (NCT NCT01426958)
NCT ID: NCT01426958
Last Updated: 2014-06-09
Results Overview
AUC0-tz represents the area under the concentration curve of the analyte in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte.
COMPLETED
PHASE1
24 participants
0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
2014-06-09
Participant Flow
Participant milestones
| Measure |
All Participants
This is an open-label, randomized, three-way crossover clinical phase I trial in healthy volunteers.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
22
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
All Participants
This is an open-label, randomized, three-way crossover clinical phase I trial in healthy volunteers.
|
|---|---|
|
Overall Study
Adverse Event
|
2
|
Baseline Characteristics
Investigation of Ritonavir Effects on Afatinib Exposure in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Overall Study
n=24 Participants
This is an open-label, randomized, three-way crossover clinical phase I trial in healthy volunteers.
|
|---|---|
|
Age, Continuous
|
38.0 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours postPopulation: This subject set includes all evaluable subjects of the treated set who were assigned to the final dose groups and who provide at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.
AUC0-tz represents the area under the concentration curve of the analyte in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte.
Outcome measures
| Measure |
Afatinib
n=21 Participants
Subjects were treated with a single dose of Afatinib 40mg on Day 1.
|
Afatinib + Concomittant Rtv
n=24 Participants
Subjects were treated with Ritonavir (Rtv) 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 with third Rtv dose.
|
Afatinib + Timed Rtv
n=22 Participants
Subjects were treated with Rtv 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 six hours prior to third Rtv dose.
|
|---|---|---|---|
|
Area Under Curve From 0 to tz (AUC0-tz)
|
392 ng*h/mL
Geometric Coefficient of Variation 26.2
|
478 ng*h/mL
Geometric Coefficient of Variation 27.9
|
438 ng*h/mL
Geometric Coefficient of Variation 20.3
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours postPopulation: This subject set includes all evaluable subjects of the treated set who were assigned to the final dose groups and who provide at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.
Cmax represents the maximum concentration of the analyte in plasma.
Outcome measures
| Measure |
Afatinib
n=22 Participants
Subjects were treated with a single dose of Afatinib 40mg on Day 1.
|
Afatinib + Concomittant Rtv
n=24 Participants
Subjects were treated with Ritonavir (Rtv) 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 with third Rtv dose.
|
Afatinib + Timed Rtv
n=22 Participants
Subjects were treated with Rtv 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 six hours prior to third Rtv dose.
|
|---|---|---|---|
|
Maximum Concentration (Cmax)
|
19.5 ng/mL
Geometric Coefficient of Variation 33.5
|
20.7 ng/mL
Geometric Coefficient of Variation 29.4
|
20.7 ng/mL
Geometric Coefficient of Variation 24.4
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours postPopulation: This subject set includes all evaluable subjects of the treated set who were assigned to the final dose groups and who provide at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.
AUC0-∞ represents the area under the concentration curve of the analyte in plasma from 0 extrapolated to infinity.
Outcome measures
| Measure |
Afatinib
n=22 Participants
Subjects were treated with a single dose of Afatinib 40mg on Day 1.
|
Afatinib + Concomittant Rtv
n=24 Participants
Subjects were treated with Ritonavir (Rtv) 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 with third Rtv dose.
|
Afatinib + Timed Rtv
n=22 Participants
Subjects were treated with Rtv 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 six hours prior to third Rtv dose.
|
|---|---|---|---|
|
Area Under Curve From 0 to ∞ Hours (AUC0-∞)
|
426 ng*h/mL
Geometric Coefficient of Variation 22.8
|
515 ng*h/mL
Geometric Coefficient of Variation 27.5
|
475 ng*h/mL
Geometric Coefficient of Variation 19.4
|
Adverse Events
Afatinib
Afatinib + Concomittant Rtv
Afatinib + Timed Rtv
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Afatinib
n=23 participants at risk
Subjects were treated with a single dose of Afatinib 40mg on Day 1.
|
Afatinib + Concomittant Rtv
n=24 participants at risk
Subjects were treated with Ritonavir (Rtv) 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 with third Rtv dose.
|
Afatinib + Timed Rtv
n=22 participants at risk
Subjects were treated with Rtv 2x100mg twice daily (bid) on Days -1, 1 and 2 and with a single dose of Afatinib 40mg on Day 1 six hours prior to third Rtv dose.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/23 • First administration of trial medication until 28 days after last administration of trial medication
|
12.5%
3/24 • First administration of trial medication until 28 days after last administration of trial medication
|
18.2%
4/22 • First administration of trial medication until 28 days after last administration of trial medication
|
|
Investigations
Lipase increased
|
0.00%
0/23 • First administration of trial medication until 28 days after last administration of trial medication
|
8.3%
2/24 • First administration of trial medication until 28 days after last administration of trial medication
|
0.00%
0/22 • First administration of trial medication until 28 days after last administration of trial medication
|
|
Nervous system disorders
Headache
|
8.7%
2/23 • First administration of trial medication until 28 days after last administration of trial medication
|
0.00%
0/24 • First administration of trial medication until 28 days after last administration of trial medication
|
4.5%
1/22 • First administration of trial medication until 28 days after last administration of trial medication
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/23 • First administration of trial medication until 28 days after last administration of trial medication
|
8.3%
2/24 • First administration of trial medication until 28 days after last administration of trial medication
|
0.00%
0/22 • First administration of trial medication until 28 days after last administration of trial medication
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER