Trial Outcomes & Findings for Bioequivalence Trial of 2 Dose Strengths of BI 201335 NA Soft Gelatine Capsules (NCT NCT01704846)

NCT ID: NCT01704846

Last Updated: 2015-07-31

Results Overview

Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 to the time of the last quantifiable data point. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Results posted on

2015-07-31

Participant Flow

Participant milestones

Participant milestones
Measure
Treatment Sequence 1
Treatment sequence: Test - Reference - Reference - Test Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast. Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast. Treatments were separated by a washout period of at least 14 days.
Treatment Sequence 2
Treatment sequence: Reference - Test - Test - Reference Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast. Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast. Treatments were separated by a washout period of at least 14 days.
Treatment Period 1
STARTED
30
30
Treatment Period 1
COMPLETED
30
30
Treatment Period 1
NOT COMPLETED
0
0
Treatment Period 2
STARTED
30
30
Treatment Period 2
COMPLETED
30
29
Treatment Period 2
NOT COMPLETED
0
1
Treatment Period 3
STARTED
30
29
Treatment Period 3
COMPLETED
30
29
Treatment Period 3
NOT COMPLETED
0
0
Treatment Period 4
STARTED
30
29
Treatment Period 4
COMPLETED
30
29
Treatment Period 4
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Treatment Sequence 1
Treatment sequence: Test - Reference - Reference - Test Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast. Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast. Treatments were separated by a washout period of at least 14 days.
Treatment Sequence 2
Treatment sequence: Reference - Test - Test - Reference Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast. Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast. Treatments were separated by a washout period of at least 14 days.
Treatment Period 2
Withdrawal by Subject
0
1

Baseline Characteristics

Bioequivalence Trial of 2 Dose Strengths of BI 201335 NA Soft Gelatine Capsules

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment Sequence 1
n=30 Participants
Treatment sequence: Test - Reference - Reference - Test Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast. Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast. Treatments were separated by a washout period of at least 14 days.
Treatment Sequence 2
n=30 Participants
Treatment sequence: Reference - Test - Test - Reference Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast. Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast. Treatments were separated by a washout period of at least 14 days.
Total
n=60 Participants
Total of all reporting groups
Age, Continuous
28.1 years
STANDARD_DEVIATION 5.7 • n=5 Participants
30.1 years
STANDARD_DEVIATION 5.8 • n=7 Participants
29.1 years
STANDARD_DEVIATION 5.8 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Male
30 Participants
n=5 Participants
30 Participants
n=7 Participants
60 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.

Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 to the time of the last quantifiable data point. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.

Outcome measures

Outcome measures
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=118 Observations
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=119 Observations
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Area Under the Curve of the Analyte From Time 0 to the Last Quantifiable Data Point (AUC0-tz)
17297.157 ng·h/mL
Geometric Coefficient of Variation 19.71
17216.514 ng·h/mL
Geometric Coefficient of Variation 23.89

PRIMARY outcome

Timeframe: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.

Maximum measured concentration of faldaprevir in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.

Outcome measures

Outcome measures
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=118 Observations
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=119 Observations
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Maximum Measured Concentration (Cmax)
943.868 ng/mL
Geometric Coefficient of Variation 32.16
916.480 ng/mL
Geometric Coefficient of Variation 39.22

SECONDARY outcome

Timeframe: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.

Area under the concentration-time curve of faldaprevir in plasma over the time interval from 0 extrapolated to infinity. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.

Outcome measures

Outcome measures
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=118 Observations
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=119 Observations
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
18422.006 ng*h/mL
Geometric Coefficient of Variation 19.07
18323.189 ng*h/mL
Geometric Coefficient of Variation 23.18

SECONDARY outcome

Timeframe: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.

Time from dosing to the maximum measured concentration of the analyte in plasma. Means presented are adjusted means and the standard deviation is actually the intra-individual coefficient of variation.

Outcome measures

Outcome measures
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=118 Observations
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=119 Observations
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Time From Dosing to the Maximum Measured Concentration (Tmax)
4.478 hours
Standard Deviation 25.60 • Interval 2.0 to 8.0
4.585 hours
Standard Deviation 31.48 • Interval 2.0 to 10.0

SECONDARY outcome

Timeframe: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.

Terminal rate constant of the analyte in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.

Outcome measures

Outcome measures
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=118 Observations
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=119 Observations
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Terminal Rate Constant (λz)
0.0265 1/h
Geometric Coefficient of Variation 9.91
0.0264 1/h
Geometric Coefficient of Variation 6.91

SECONDARY outcome

Timeframe: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.

Terminal half-life of faldaprevir in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.

Outcome measures

Outcome measures
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=118 Observations
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=119 Observations
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Terminal Half-life (t1/2)
26.204 hours
Geometric Coefficient of Variation 9.91
26.293 hours
Geometric Coefficient of Variation 6.91

SECONDARY outcome

Timeframe: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.

Mean residence time of the analyte in the body after oral administration. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.

Outcome measures

Outcome measures
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=118 Observations
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=119 Observations
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Mean Residence Time (MRTpo)
29.948 hour
Geometric Coefficient of Variation 9.93
29.888 hour
Geometric Coefficient of Variation 9.79

Adverse Events

Test Product: Faldaprevir 40 mg x 3 Capsules

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Reference Product: Faldaprevir 120 mg x 1 Capsule

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Test Product: Faldaprevir 40 mg x 3 Capsules
n=59 participants at risk
Faldaprevir 120 mg (40 mg x 3 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Reference Product: Faldaprevir 120 mg x 1 Capsule
n=60 participants at risk
Faldaprevir 120 mg (120 mg x 1 capsules) - soft gelatine capsule- Oral administration with 150 mL water after an overnight fast
Gastrointestinal disorders
Diarrhoea
5.1%
3/59 • Four treatment periods (Period 1 to 4) of 6 days for each (Days -1 to 5) + Washout period of at least 14 days between treatments
5.0%
3/60 • Four treatment periods (Period 1 to 4) of 6 days for each (Days -1 to 5) + Washout period of at least 14 days between treatments
Gastrointestinal disorders
Gastroenteritis
6.8%
4/59 • Four treatment periods (Period 1 to 4) of 6 days for each (Days -1 to 5) + Washout period of at least 14 days between treatments
8.3%
5/60 • Four treatment periods (Period 1 to 4) of 6 days for each (Days -1 to 5) + Washout period of at least 14 days between treatments

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER