Trial Outcomes & Findings for Effect of Multiple Dosing With BI 201335 on the Pharmacokinetics of Darunavir Co-administered With Ritonavir in Healthy Male and Female Volunteers (NCT NCT01374802)

Last Updated: 2015-07-31

Results Overview

area under the concentration-time curve of the analyte in plasma at steadystate over a uniform dosing interval τ of darunavir. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)

Results posted on

2015-07-31

Participant Flow

Participant milestones

Participant milestones
Measure	All Subjects The study was performed as an open-label, multiple-dose, single-group, fixed-sequence study in 14 healthy volunteers. Period 1: Darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r). Period 2: Faldaprevir together with DRV/r.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Multiple Dosing With BI 201335 on the Pharmacokinetics of Darunavir Co-administered With Ritonavir in Healthy Male and Female Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Subjects n=14 Participants The study was performed as an open-label, multiple-dose, single-group, fixed-sequence study in 14 healthy volunteers. Period 1: darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r). Period 2: faldaprevir together with DRV/r.
Age, Continuous	40.4 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)

Population: Pharmacokinetic (PK) set: all subjects in the treated set who provided at least one observation for at least one primary endpoint without any important protocol violations relevant to the pharmacokinetic evaluation and who did not experience vomiting at or before 2 times median tmax.

Outcome measures

Outcome measures
Measure	Darunavir+Ritonavir n=14 Participants oral administration of darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r) once daily	Faldaprevir+Darunavir+Ritonavir n=14 Participants oral administration of Faldaprevir 240 mg once daily together with DRV/r. Faldaprevir 480 mg loading dose together with DRV/r on the first day.
AUCτ,ss of Darunavir	57200 ng*h/mL Geometric Coefficient of Variation 29.5	66000 ng*h/mL Geometric Coefficient of Variation 39.9

PRIMARY outcome

Timeframe: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)

Population: PK set

concentration of the analyte in plasma at steady-state after a uniform dosing interval τ=24h of darunavir

Outcome measures

Outcome measures
Measure	Darunavir+Ritonavir n=14 Participants oral administration of darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r) once daily	Faldaprevir+Darunavir+Ritonavir n=14 Participants oral administration of Faldaprevir 240 mg once daily together with DRV/r. Faldaprevir 480 mg loading dose together with DRV/r on the first day.
Cτ,ss of Darunavir	1330 ng/mL Geometric Coefficient of Variation 49.5	1170 ng/mL Geometric Coefficient of Variation 90.3

PRIMARY outcome

Timeframe: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)

Population: PK set

maximum measured concentration of the analyte in plasma at steady-state

Outcome measures

Outcome measures
Measure	Darunavir+Ritonavir n=14 Participants oral administration of darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r) once daily	Faldaprevir+Darunavir+Ritonavir n=14 Participants oral administration of Faldaprevir 240 mg once daily together with DRV/r. Faldaprevir 480 mg loading dose together with DRV/r on the first day.
Cmax,ss of Darunavir	4930 ng/mL Geometric Coefficient of Variation 23.9	6330 ng/mL Geometric Coefficient of Variation 26.5

SECONDARY outcome

Timeframe: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)

Population: PK set

time from last dosing to maximum concentration of the analyte in plasma at steady state

Outcome measures

Outcome measures
Measure	Darunavir+Ritonavir n=14 Participants oral administration of darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r) once daily	Faldaprevir+Darunavir+Ritonavir n=14 Participants oral administration of Faldaprevir 240 mg once daily together with DRV/r. Faldaprevir 480 mg loading dose together with DRV/r on the first day.
Tmax,ss of Darunavir	1.50 h Full Range 33.9 • Interval 1.0 to 3.0	2.01 h Full Range 37.3 • Interval 1.0 to 4.0

Adverse Events

Darunavir+Ritonavir

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Faldaprevir+Darunavir+Ritonavir

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

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

Measure	Darunavir+Ritonavir n=14 participants at risk oral administration of darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r)once daily	Faldaprevir+Darunavir+Ritonavir n=14 participants at risk oral administration of Faldaprevir 240 mg once daily together with DRV/r. Faldaprevir 480 mg loading dose together with DRV/r on the first day.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Psychiatric disorders Insomnia	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Psychiatric disorders Nervousness	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Psychiatric disorders Sleep disorder	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Nervous system disorders Headache	14.3% 2/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	21.4% 3/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Nervous system disorders Dizziness	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Nervous system disorders Somnolence	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Eye disorders Eye haemorrhage	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Vascular disorders Hot flush	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Gastrointestinal disorders Diarrhoea	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	42.9% 6/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Gastrointestinal disorders Abdominal distension	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	28.6% 4/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Gastrointestinal disorders Nausea	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	14.3% 2/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Gastrointestinal disorders Flatulence	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Gastrointestinal disorders Vomiting	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	7.1% 1/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.
General disorders Fatigue	21.4% 3/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.	0.00% 0/14 • Adverse events (AEs) occurring up to 9 days after first drug administration of DRV/r were assigned to the treatment DRV/r and AEs occurring up to 13 days after last drug administration of DRV/r+FDV were assigned to the combined treatment DRV/r+FDV. The subjects were required to spontaneously report any AEs. In addition, subjects were assessed regularly for AEs during the trial.