Trial Outcomes & Findings for Bioavailability Study of Oral OZ439 Prototype Formulations Administered With Piperaquine Phosphate (PQP) (NCT NCT02083406)
NCT ID: NCT02083406
Last Updated: 2015-03-23
Results Overview
OZ439 Area under the plasma concentration (AUC) versus time curve
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
Up to 168 hours post-dose
Results posted on
2015-03-23
Participant Flow
Participant milestones
| Measure |
Treatment A: OZ439 Prototype 1
800mg OZ439 prototype formulation 1 and 960mg PQP single doses under fasted conditions
|
Treatment B: OZ439 Prototype 2
800mg OZ439 prototype formulation 2 and 960mg PQP single doses under fasted conditions
|
Treatment C: OZ439 Prototype 3
800mg OZ439 prototype formulation 3 and 960mg PQP single doses under fasted conditions
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
8
|
7
|
|
Overall Study
COMPLETED
|
7
|
8
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioavailability Study of Oral OZ439 Prototype Formulations Administered With Piperaquine Phosphate (PQP)
Baseline characteristics by cohort
| Measure |
Treatment A: OZ439 Prototype 1
n=7 Participants
800mg OZ439 prototype formulation 1 and 960mg PQP single doses under fasted conditions
|
Treatment B: OZ439 Prototype 2
n=8 Participants
800mg OZ439 prototype formulation 2 and 960mg PQP single doses under fasted conditions
|
Treatment C: OZ439 Prototype 3
n=7 Participants
800mg OZ439 prototype formulation 3 and 960mg PQP single doses under fasted conditions
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
28 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
44.9 years
STANDARD_DEVIATION 11.3 • n=7 Participants
|
35.7 years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
36.6 years
STANDARD_DEVIATION 10.9 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
7 participants
n=5 Participants
|
8 participants
n=7 Participants
|
7 participants
n=5 Participants
|
22 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 168 hours post-dosePopulation: All subjects who received at least one dose of study drug and had sufficient plasma concentration data for pharmacokinetics (PK) parameter estimation
OZ439 Area under the plasma concentration (AUC) versus time curve
Outcome measures
| Measure |
Treatment A: OZ439 Prototype 1
n=7 Participants
800mg OZ439 prototype formulation 1 and 960mg PQP single doses under fasted conditions
|
Treatment B: OZ439 Prototype 2
n=8 Participants
800mg OZ439 prototype formulation 2 and 960mg PQP single doses under fasted conditions
|
Treatment C: OZ439 Prototype 3
n=7 Participants
800mg OZ439 prototype formulation 3 and 960mg PQP single doses under fasted conditions
|
|---|---|---|---|
|
OZ439 AUC(0-168h)
|
8780 ng*h/mL
Geometric Coefficient of Variation 43.7
|
10300 ng*h/mL
Geometric Coefficient of Variation 23.7
|
9460 ng*h/mL
Geometric Coefficient of Variation 43.0
|
PRIMARY outcome
Timeframe: Up to 168 hours post-dosePopulation: All subjects who received at least one dose of study drug and had sufficient plasma concentration data for PK parameter estimation
OZ439 Maximum observed concentration
Outcome measures
| Measure |
Treatment A: OZ439 Prototype 1
n=7 Participants
800mg OZ439 prototype formulation 1 and 960mg PQP single doses under fasted conditions
|
Treatment B: OZ439 Prototype 2
n=8 Participants
800mg OZ439 prototype formulation 2 and 960mg PQP single doses under fasted conditions
|
Treatment C: OZ439 Prototype 3
n=7 Participants
800mg OZ439 prototype formulation 3 and 960mg PQP single doses under fasted conditions
|
|---|---|---|---|
|
OZ439 Cmax
|
877 ng/mL
Geometric Coefficient of Variation 41.3
|
995 ng/mL
Geometric Coefficient of Variation 32.2
|
924 ng/mL
Geometric Coefficient of Variation 50.5
|
SECONDARY outcome
Timeframe: Up to 168h post-dosePopulation: All subjects who received at least one dose of study drug and had sufficient plasma concentration data for PK parameter estimation
PQ Area under the plasma concentration versus time curve
Outcome measures
| Measure |
Treatment A: OZ439 Prototype 1
n=7 Participants
800mg OZ439 prototype formulation 1 and 960mg PQP single doses under fasted conditions
|
Treatment B: OZ439 Prototype 2
n=8 Participants
800mg OZ439 prototype formulation 2 and 960mg PQP single doses under fasted conditions
|
Treatment C: OZ439 Prototype 3
n=7 Participants
800mg OZ439 prototype formulation 3 and 960mg PQP single doses under fasted conditions
|
|---|---|---|---|
|
Piperaquine (PQ) AUC(0-168h)
|
3730 ng*h/mL
Geometric Coefficient of Variation 41.3
|
2810 ng*h/mL
Geometric Coefficient of Variation 21.8
|
3300 ng*h/mL
Geometric Coefficient of Variation 50.7
|
SECONDARY outcome
Timeframe: Up to 168h post-dosePopulation: All subjects who received at least one dose of study drug and had sufficient plasma concentration data for PK parameter estimation
PQ Maximum observed concentration
Outcome measures
| Measure |
Treatment A: OZ439 Prototype 1
n=7 Participants
800mg OZ439 prototype formulation 1 and 960mg PQP single doses under fasted conditions
|
Treatment B: OZ439 Prototype 2
n=8 Participants
800mg OZ439 prototype formulation 2 and 960mg PQP single doses under fasted conditions
|
Treatment C: OZ439 Prototype 3
n=7 Participants
800mg OZ439 prototype formulation 3 and 960mg PQP single doses under fasted conditions
|
|---|---|---|---|
|
PQ Cmax
|
99.8 ng/mL
Geometric Coefficient of Variation 90.1
|
89.5 ng/mL
Geometric Coefficient of Variation 54.1
|
91.2 ng/mL
Geometric Coefficient of Variation 130.8
|
Adverse Events
Treatment A: OZ439 Prototype 1
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Treatment B: OZ439 Prototype 2
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Treatment C: OZ439 Prototype 3
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: OZ439 Prototype 1
n=7 participants at risk
800mg OZ439 prototype formulation 1 and 960mg PQP single doses under fasted conditions
|
Treatment B: OZ439 Prototype 2
n=8 participants at risk
800mg OZ439 prototype formulation 2 and 960mg PQP single doses under fasted conditions
|
Treatment C: OZ439 Prototype 3
n=7 participants at risk
800mg OZ439 prototype formulation 3 and 960mg PQP single doses under fasted conditions
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
14.3%
1/7 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
25.0%
2/8 • Number of events 2 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
14.3%
1/7 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/8 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
14.3%
1/7 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Infections and infestations
Tonsillitis
|
14.3%
1/7 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/8 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
14.3%
1/7 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Nervous system disorders
Headache
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
General disorders
Cyst
|
14.3%
1/7 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/8 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
0.00%
0/7 • Up to Day 43 post-dose
All 22 subjects received one dose of OZ439 in combination with PQP and were included in the safety analysis population
|
Additional Information
Fiona Macintyre, PhD
Medicines for Malaria Venture (MMV)
Phone: +41 22 555 0319
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place