Trial Outcomes & Findings for A Comparison of the Bioavailability of OZ439 When Delivered Directly to the Small Intestine, or Via the Oral Route (NCT NCT01732588)
NCT ID: NCT01732588
Last Updated: 2015-03-06
Results Overview
Area under the plasma concentration-time curve from zero to infinity (AUC0-∞)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
11 participants
Primary outcome timeframe
pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose
Results posted on
2015-03-06
Participant Flow
Participant milestones
| Measure |
Sequence 1
Subjects received a single dose of 120 mg OZ439 PIB oral suspension (Regimen A), then 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C)
|
Sequence 2
Subjects received a single dose of 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A).
|
Sequence 3
Subjects received a single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A); then 120 mg OZ439 IR caplet (Regimen B).
|
|---|---|---|---|
|
First Intervention (7 Days)
STARTED
|
4
|
3
|
4
|
|
First Intervention (7 Days)
COMPLETED
|
4
|
2
|
4
|
|
First Intervention (7 Days)
NOT COMPLETED
|
0
|
1
|
0
|
|
Second Intervention (7 Days)
STARTED
|
4
|
2
|
4
|
|
Second Intervention (7 Days)
COMPLETED
|
4
|
2
|
4
|
|
Second Intervention (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Third Intervention (7 Days)
STARTED
|
4
|
2
|
4
|
|
Third Intervention (7 Days)
COMPLETED
|
4
|
2
|
4
|
|
Third Intervention (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
Subjects received a single dose of 120 mg OZ439 PIB oral suspension (Regimen A), then 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C)
|
Sequence 2
Subjects received a single dose of 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A).
|
Sequence 3
Subjects received a single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A); then 120 mg OZ439 IR caplet (Regimen B).
|
|---|---|---|---|
|
First Intervention (7 Days)
Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
A Comparison of the Bioavailability of OZ439 When Delivered Directly to the Small Intestine, or Via the Oral Route
Baseline characteristics by cohort
| Measure |
Sequence 1
n=4 Participants
Subjects received a single dose of 120 mg OZ439 PIB oral suspension (Regimen A), then 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C)
|
Sequence 2
n=3 Participants
Subjects received a single dose of 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A)
|
Sequence 3
n=4 Participants
Subjects received a single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A); then 120 mg OZ439 IR caplet (Regimen B).
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
41.5 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
35.3 years
STANDARD_DEVIATION 14.6 • n=7 Participants
|
36.8 years
STANDARD_DEVIATION 12.3 • n=5 Participants
|
38.1 years
STANDARD_DEVIATION 11.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
11 participants
n=4 Participants
|
|
Body Mass Index
|
26.50 kg/m^2
STANDARD_DEVIATION 3.7 • n=5 Participants
|
24.67 kg/m^2
STANDARD_DEVIATION 0.58 • n=7 Participants
|
26.75 kg/m^2
STANDARD_DEVIATION 1.89 • n=5 Participants
|
26.09 kg/m^2
STANDARD_DEVIATION 2.47 • n=4 Participants
|
|
weight
|
82.53 kg
STANDARD_DEVIATION 13.44 • n=5 Participants
|
68 kg
STANDARD_DEVIATION 8.86 • n=7 Participants
|
80.83 kg
STANDARD_DEVIATION 1.44 • n=5 Participants
|
77.95 kg
STANDARD_DEVIATION 10.58 • n=4 Participants
|
PRIMARY outcome
Timeframe: pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dosePopulation: PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation. In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.
Area under the plasma concentration-time curve from zero to infinity (AUC0-∞)
Outcome measures
| Measure |
Regimen A - OZ439 120mg PIB
n=9 Participants
Single dose of 120 mg OZ439 powder in bottle (PIB) oral suspension
|
Regimen B - 120 mg OZ439 IR Caplet
n=10 Participants
Single dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate
|
Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule
n=9 Participants
Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule
|
|---|---|---|---|
|
OZ439 AUC0-∞
|
1230 ng*h/mL
Geometric Coefficient of Variation 46.5
|
907 ng*h/mL
Geometric Coefficient of Variation 46.3
|
398 ng*h/mL
Geometric Coefficient of Variation 99
|
PRIMARY outcome
Timeframe: pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dosePopulation: PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation. In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.
The maximum observed plasma drug concentrations (Cmax)
Outcome measures
| Measure |
Regimen A - OZ439 120mg PIB
n=9 Participants
Single dose of 120 mg OZ439 powder in bottle (PIB) oral suspension
|
Regimen B - 120 mg OZ439 IR Caplet
n=10 Participants
Single dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate
|
Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule
n=9 Participants
Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule
|
|---|---|---|---|
|
OZ439 Cmax
|
180 ng/mL
Geometric Coefficient of Variation 50.5
|
82.7 ng/mL
Geometric Coefficient of Variation 73.5
|
35.4 ng/mL
Geometric Coefficient of Variation 98.7
|
SECONDARY outcome
Timeframe: pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dosePopulation: PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation. In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.
Time of maximum observed plasma drug concentrations (Tmax)
Outcome measures
| Measure |
Regimen A - OZ439 120mg PIB
n=9 Participants
Single dose of 120 mg OZ439 powder in bottle (PIB) oral suspension
|
Regimen B - 120 mg OZ439 IR Caplet
n=10 Participants
Single dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate
|
Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule
n=9 Participants
Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule
|
|---|---|---|---|
|
OZ439 Tmax
|
2 hours
Interval 2.0 to 4.0
|
4 hours
Interval 2.0 to 6.0
|
4 hours
Interval 2.0 to 4.0
|
Adverse Events
Regimen A - 120mg OZ439 PIB
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Regimen B - 120 mg OZ439 IR Caplet
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Regimen A - 120mg OZ439 PIB
n=10 participants at risk
Single oral dose of 120 mg OZ439 as powder in bottle (PIB) formulation.
|
Regimen B - 120 mg OZ439 IR Caplet
n=11 participants at risk
Single oral dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate
|
Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule
n=10 participants at risk
Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate administered orally via the Enterion capsule
|
|---|---|---|---|
|
Gastrointestinal disorders
abdominal pain
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Gastrointestinal disorders
diarrhoea
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Gastrointestinal disorders
vomiting
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Investigations
increased alanine aminotransferase
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Investigations
increased aspartate aminotransferase
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Investigations
abnormal electrocardiogram
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
9.1%
1/11 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Investigations
abnormal urine analysis
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Nervous system disorders
headache
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
20.0%
2/10 • Number of events 2 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
General disorders
vessel puncture site haematoma
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
9.1%
1/11 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Infections and infestations
Upper respiratory tract infection
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
|
Skin and subcutaneous tissue disorders
rash
|
0.00%
0/10 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
0.00%
0/11 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
10.0%
1/10 • Number of events 1 • Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.
The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60