Trial Outcomes & Findings for Drug Drug Interaction of BI 201335 and Tenofovir (NCT NCT01340196)
NCT ID: NCT01340196
Last Updated: 2015-07-31
Results Overview
Area under the concentration-time curve (AUC) of the analyte in plasma over the time interval 0-24 hours, at steady state.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15
Results posted on
2015-07-31
Participant Flow
Participant milestones
| Measure |
All Participants
tenofovir medium dose (300mg) once daily (qd, oral) for first 15 days; Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (300mg) twice daily (bid) on days 9 through day 22 (morning dose on day 22 only)
|
|---|---|
|
Treat. Period 1 (Tenofovir)
STARTED
|
16
|
|
Treat. Period 1 (Tenofovir)
COMPLETED
|
16
|
|
Treat. Period 1 (Tenofovir)
NOT COMPLETED
|
0
|
|
Treat. Period 2 (Tenofovir/Faldaprevir)
STARTED
|
16
|
|
Treat. Period 2 (Tenofovir/Faldaprevir)
COMPLETED
|
16
|
|
Treat. Period 2 (Tenofovir/Faldaprevir)
NOT COMPLETED
|
0
|
|
Treat. Period 3 (Faldaprevir)
STARTED
|
16
|
|
Treat. Period 3 (Faldaprevir)
COMPLETED
|
14
|
|
Treat. Period 3 (Faldaprevir)
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
All Participants
tenofovir medium dose (300mg) once daily (qd, oral) for first 15 days; Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (300mg) twice daily (bid) on days 9 through day 22 (morning dose on day 22 only)
|
|---|---|
|
Treat. Period 3 (Faldaprevir)
Adverse Event
|
2
|
Baseline Characteristics
Drug Drug Interaction of BI 201335 and Tenofovir
Baseline characteristics by cohort
| Measure |
All Participants
n=16 Participants
tenofovir medium dose (300mg) once daily (qd, oral) for first 15 days; Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (300mg) twice daily (bid) on days 9 through day 22 (morning dose on day 22 only)
|
|---|---|
|
Age, Continuous
|
37 years
STANDARD_DEVIATION 8.6 • n=93 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15Population: All participants from the pharmacokinetic analysis set (PK set), including all subjects who were documented to have taken at least one dose of trial medication (treated set) who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve (AUC) of the analyte in plasma over the time interval 0-24 hours, at steady state.
Outcome measures
| Measure |
Tenofovir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Steady-state Pharmacokinetics of AUC0-24 of Tenofovir on Day 7 and on Day 15
|
2700 ng*h/mL
Geometric Coefficient of Variation 26.5 • Interval 0.0 to 0.0
|
3290 ng*h/mL
Geometric Coefficient of Variation 19.6 • Interval 0.0 to 0.0
|
—
|
PRIMARY outcome
Timeframe: 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00. 192:00 hours on day 15Population: All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Maximum measured concentration of analyte in plasma (Cmax), at steady state.
Outcome measures
| Measure |
Tenofovir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Steady-state Pharmacokinetics of Cmax of Tenofovir on Day 7 and on Day 15
|
300 ng/mL
Geometric Coefficient of Variation 27.3
|
284 ng/mL
Geometric Coefficient of Variation 16.6
|
—
|
PRIMARY outcome
Timeframe: 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15Population: All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Measured concentration of the analyte in plasma at 24 h (C24hr) after dosing, at steady state.
Outcome measures
| Measure |
Tenofovir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Steady-state Pharmacokinetics of C24hr of Tenofovir on Day 7 and on Day 15
|
54.0 ng/mL
Geometric Coefficient of Variation 26.7
|
79.4 ng/mL
Geometric Coefficient of Variation 21.5
|
—
|
PRIMARY outcome
Timeframe: 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22Population: All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve (AUC) of the analyte in plasma over the time interval 0-12 hours, at steady state.
Outcome measures
| Measure |
Tenofovir
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
n=14 Participants
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Steady-state Pharmacokinetics of AUC0-12 of Faldaprevir on Day 15 and on Day 22
|
—
|
418000 ng*h/mL
Geometric Coefficient of Variation 69.3
|
523000 ng*h/mL
Geometric Coefficient of Variation 101
|
PRIMARY outcome
Timeframe: 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22Population: All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Maximum measured concentration of analyte in plasma (Cmax), at steady state.
Outcome measures
| Measure |
Tenofovir
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
n=14 Participants
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Steady-state Pharmacokinetics of Cmax of Faldaprevir on Day 15 and Day 22
|
—
|
41700 ng/mL
Geometric Coefficient of Variation 51.4
|
50400 ng/mL
Geometric Coefficient of Variation 91.3
|
PRIMARY outcome
Timeframe: 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22Population: All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Measured concentration of the analyte in plasma at 12 h (C12hr) after dosing, at steady state.
Outcome measures
| Measure |
Tenofovir
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
n=14 Participants
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Steady-state Pharmacokinetics of C12hr of Faldaprevir on Day 15 and on Day 22
|
—
|
31000 ng/mL
Geometric Coefficient of Variation 79.5
|
40000 ng/mL
Geometric Coefficient of Variation 113
|
SECONDARY outcome
Timeframe: From drug administration up to 32 days.Population: All subjects who were dispensed study medication and were documented to have taken at least one dose of study drug were included in the safety evaluation (treated set).
Outcome data are the numbers of subjects with investigator defined drug-related AEs
Outcome measures
| Measure |
Tenofovir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
n=16 Participants
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Number of Patients With Drug Related Adverse Events During the Trial
|
0 participants
|
15 participants
|
9 participants
|
SECONDARY outcome
Timeframe: From drug administration up to 32 days.Population: All subjects who were dispensed study medication and were documented to have taken at least one dose of study drug were included in the safety evaluation (treated set).
Clinical relevant abnormalities for physical examination, vital signs, safety laboratory tests and 12-lead ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Preferred term of relevant AE: Presyncope
Outcome measures
| Measure |
Tenofovir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 Participants
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
n=16 Participants
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Safety Laboratory Tests and 12-lead ECG
|
1 participants
|
0 participants
|
0 participants
|
Adverse Events
Tenofovir
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Tenofovir/Faldaprevir
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Faldaprevir
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tenofovir
n=16 participants at risk
tenofovir medium dose (300mg) once daily (qd) (day 1 to 7)
|
Tenofovir/Faldaprevir
n=16 participants at risk
tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15
|
Faldaprevir
n=16 participants at risk
Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22)
|
|---|---|---|---|
|
Infections and infestations
Oral herpes
|
0.00%
0/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/16 • From drug administration up to 32 days
|
12.5%
2/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Nervous system disorders
Headache
|
0.00%
0/16 • From drug administration up to 32 days
|
62.5%
10/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Nervous system disorders
Presyncope
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Nervous system disorders
Tremor
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Eye disorders
Ocular icterus
|
0.00%
0/16 • From drug administration up to 32 days
|
18.8%
3/16 • From drug administration up to 32 days
|
12.5%
2/16 • From drug administration up to 32 days
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/16 • From drug administration up to 32 days
|
43.8%
7/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/16 • From drug administration up to 32 days
|
37.5%
6/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/16 • From drug administration up to 32 days
|
25.0%
4/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/16 • From drug administration up to 32 days
|
12.5%
2/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/16 • From drug administration up to 32 days
|
18.8%
3/16 • From drug administration up to 32 days
|
12.5%
2/16 • From drug administration up to 32 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/16 • From drug administration up to 32 days
|
25.0%
4/16 • From drug administration up to 32 days
|
18.8%
3/16 • From drug administration up to 32 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
|
General disorders
Malaise
|
0.00%
0/16 • From drug administration up to 32 days
|
12.5%
2/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
|
General disorders
Pain
|
0.00%
0/16 • From drug administration up to 32 days
|
6.2%
1/16 • From drug administration up to 32 days
|
0.00%
0/16 • From drug administration up to 32 days
|
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