Trial Outcomes & Findings for Influence of OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Bosentan Before and During Clarithromycin (NCT NCT01425229)
NCT ID: NCT01425229
Last Updated: 2017-05-31
Results Overview
AUC of bosentan after first-dose, at steady-state and during clarithromycin therapy
Recruitment status
COMPLETED
Target enrollment
16 participants
Primary outcome timeframe
0-infinity; dosing interval
Results posted on
2017-05-31
Participant Flow
Participant milestones
| Measure |
Bosentan
Bosentan pharmacokinetics
|
|---|---|
|
Bosentan Single Dose
STARTED
|
16
|
|
Bosentan Single Dose
COMPLETED
|
16
|
|
Bosentan Single Dose
NOT COMPLETED
|
0
|
|
Bosentan Steady-state
STARTED
|
16
|
|
Bosentan Steady-state
COMPLETED
|
16
|
|
Bosentan Steady-state
NOT COMPLETED
|
0
|
|
Bosentan During Clarithromycin
STARTED
|
16
|
|
Bosentan During Clarithromycin
COMPLETED
|
16
|
|
Bosentan During Clarithromycin
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Influence of OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Bosentan Before and During Clarithromycin
Baseline characteristics by cohort
| Measure |
Bosentan
n=16 Participants
Bosentan PK
|
|---|---|
|
Age, Continuous
|
31.6 years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
16 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0-infinity; dosing intervalAUC of bosentan after first-dose, at steady-state and during clarithromycin therapy
Outcome measures
| Measure |
Bosentan After First Dose
n=16 Participants
administration of bosentan 125 mg p.o. single dose
|
Bosentan at Steady-state
n=16 Participants
administration of bosentan 125 mg p.o. b.i.d. on day 2-10
|
Bosentan During Clarithromycin
n=16 Participants
administration of bosentan 125 mg p.o. b.i.d. on day 11-14 and administration of clarithromycin 500 mg p.o b.i.d. on day 11-14
|
|---|---|---|---|
|
AUC
|
11900 h*ng/ml
Interval 9730.0 to 14500.0
|
6830 h*ng/ml
Interval 5330.0 to 8750.0
|
25500 h*ng/ml
Interval 21700.0 to 29900.0
|
PRIMARY outcome
Timeframe: after first dose, at steady-state, during clarithromycinCmax after the first dose of bosentan, at steady-state, during clarithromycin
Outcome measures
| Measure |
Bosentan After First Dose
n=16 Participants
administration of bosentan 125 mg p.o. single dose
|
Bosentan at Steady-state
n=16 Participants
administration of bosentan 125 mg p.o. b.i.d. on day 2-10
|
Bosentan During Clarithromycin
n=16 Participants
administration of bosentan 125 mg p.o. b.i.d. on day 11-14 and administration of clarithromycin 500 mg p.o b.i.d. on day 11-14
|
|---|---|---|---|
|
Cmax
|
1890 ng/ml
Interval 1540.0 to 2310.0
|
1460 ng/ml
Interval 1120.0 to 1900.0
|
5570 ng/ml
Interval 4600.0 to 6740.0
|
Adverse Events
Bosentan After First Dose
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Bosentan at Steady-state
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Bosentan During Clarithromycin
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Bosentan After First Dose
n=16 participants at risk
Bosentan PK after first dose
|
Bosentan at Steady-state
n=16 participants at risk
Bosentan PK at steady-state
|
Bosentan During Clarithromycin
n=16 participants at risk
Bosentan PK during clarithromycin
|
|---|---|---|---|
|
Gastrointestinal disorders
Xerostomia
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
|
General disorders
Nasopharyngitis
|
18.8%
3/16
|
18.8%
3/16
|
12.5%
2/16
|
|
General disorders
Nasal congestion
|
25.0%
4/16
|
25.0%
4/16
|
6.2%
1/16
|
|
General disorders
Headache
|
31.2%
5/16
|
25.0%
4/16
|
31.2%
5/16
|
|
Gastrointestinal disorders
Loss of apetite
|
6.2%
1/16
|
6.2%
1/16
|
0.00%
0/16
|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16
|
6.2%
1/16
|
0.00%
0/16
|
|
Gastrointestinal disorders
Flatulence
|
6.2%
1/16
|
6.2%
1/16
|
0.00%
0/16
|
|
General disorders
Night sweats
|
6.2%
1/16
|
6.2%
1/16
|
0.00%
0/16
|
|
General disorders
Dizziness
|
6.2%
1/16
|
6.2%
1/16
|
12.5%
2/16
|
|
General disorders
Fatigue
|
6.2%
1/16
|
6.2%
1/16
|
6.2%
1/16
|
|
Gastrointestinal disorders
Epigastric pain
|
6.2%
1/16
|
6.2%
1/16
|
6.2%
1/16
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
1/16
|
6.2%
1/16
|
12.5%
2/16
|
|
Skin and subcutaneous tissue disorders
Eczema
|
6.2%
1/16
|
6.2%
1/16
|
6.2%
1/16
|
|
Investigations
increase of creatinine kinase
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
|
Investigations
Increase of aspartate transaminase
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
|
General disorders
taste disorder
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
|
General disorders
concentration difficulty
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
|
Investigations
Tachykardia
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
|
Gastrointestinal disorders
abdominal pain
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
|
General disorders
tinnitus
|
0.00%
0/16
|
0.00%
0/16
|
6.2%
1/16
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place