Trial Outcomes & Findings for Drug Interaction Study With Rifampicin and Afatinib (NCT NCT01396265)

NCT ID: NCT01396265

Last Updated: 2014-06-09

Results Overview

AUC0-∞ represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 22 participants
• Primary outcome timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
• Results posted on: 2014-06-09

Participant Flow

Participant milestones

Measure	Overall Group Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.
Afatinib STARTED	22
Afatinib COMPLETED	22
Afatinib NOT COMPLETED	0
Washout STARTED	22
Washout COMPLETED	22
Washout NOT COMPLETED	0
Rifa+Afatinib STARTED	22
Rifa+Afatinib COMPLETED	21
Rifa+Afatinib NOT COMPLETED	1

Reasons for withdrawal

Measure	Overall Group Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.
Rifa+Afatinib Withdrawal by Subject	1

Baseline Characteristics

Drug Interaction Study With Rifampicin and Afatinib

Baseline characteristics by cohort

Measure	Overall Study n=22 Participants This was a open-label, two period, fixed sequence trial clinical phase I trial in healthy male volunteers.
Age, Continuous	32.7 years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

AUC0-∞ represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Area Under Curve From 0 to Infinity Hours (AUC0-∞)	912 ng*h/mL Geometric Coefficient of Variation 38.3	610 ng*h/mL Geometric Coefficient of Variation 32.1

PRIMARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

AUC0-tz represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration.

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Area Under Curve From 0 to tz (AUC0-tz)	860 ng*h/mL Geometric Coefficient of Variation 39.8	575 ng*h/mL Geometric Coefficient of Variation 32.3

PRIMARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

Cmax represents the maximum concentration of the analyte in plasma.

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=22 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Maximum Concentration (Cmax)	38.3 ng/mL Geometric Coefficient of Variation 38.4	30.0 ng/mL Geometric Coefficient of Variation 34.1

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

tmax represents the time from dosing to the maximum concentration of the analyte in plasma

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=22 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Time From Dosing to the Maximum Concentration of Afatinib in Plasma (Tmax)	6.00 hours Interval 5.0 to 7.0	6.00 hours Interval 3.0 to 8.0

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

t1/2 represents the terminal half-life of the analyte in plasma

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Terminal Half-life of Afatinib in Plasma (t1/2)	32.8 hours Geometric Coefficient of Variation 18.4	36.0 hours Geometric Coefficient of Variation 15.1

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

AUC0-24 represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (h)

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Area Under Curve From 0 to 24 h (AUC0-24)	491 ng*h/mL Geometric Coefficient of Variation 41.4	353 ng*h/mL Geometric Coefficient of Variation 35.0

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

%AUCtz-∞ represents the percentage of the AUCtz-∞ obtained by extrapolation

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Percentage of the AUCtz-∞ Obtained by Extrapolation (%AUCtz-∞)	5.25 percentage of AUCtz-∞ Geometric Coefficient of Variation 44.8	5.48 percentage of AUCtz-∞ Geometric Coefficient of Variation 31.1

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

MRTpo represents the mean residence time of the analyte in the body after oral administration

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Mean Residence Time of Afatinib in the Body After Oral Administration (MRTpo)	36.9 hours Geometric Coefficient of Variation 14.3	35.1 hours Geometric Coefficient of Variation 14.0

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

CL/F represents the apparent clearance of the analyte in the plasma after extravascular administration

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Apparent Clearance of Afatinib in the Plasma After Extravascular Administration (CL/F)	731 mL/min Geometric Coefficient of Variation 38.3	1090 mL/min Geometric Coefficient of Variation 32.1

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose

Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.

V_z/F represents the apparent volume of distribution during the terminal phase λz following an extravascular dose

Outcome measures

Measure	Afatinib n=22 Participants Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=21 Participants Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Apparent Volume of Distribution During the Terminal Phase lambda_z Following an Extravascular Dose (V_z/F)	2080 Litres Geometric Coefficient of Variation 53.2	3410 Litres Geometric Coefficient of Variation 34.7

Adverse Events

Afatinib

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Afatinib + Rifa

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Afatinib n=22 participants at risk Subjects were treated with a single morning dose of Afatinib 40mg on Day 1.	Afatinib + Rifa n=22 participants at risk Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1.
Infections and infestations Nasopharyngitis	4.5% 1/22 • First administration of trial medication until 6 days after last administration of trial medication	9.1% 2/22 • First administration of trial medication until 6 days after last administration of trial medication
Nervous system disorders Headache	4.5% 1/22 • First administration of trial medication until 6 days after last administration of trial medication	13.6% 3/22 • First administration of trial medication until 6 days after last administration of trial medication

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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