Trial Outcomes & Findings for Open Label Pharmacokinetic Study of OZ439 and Piperaquine on Administration of OZ439+TPGS Granules for Oral Suspension Alone or With Either Piperaquine Phosphate Tablets or Granules for Oral Solution in Healthy Volunteers (NCT NCT01958619)
NCT ID: NCT01958619
Last Updated: 2015-05-08
Results Overview
OZ439 observed maximum drug plasma concentration
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
55 participants
Primary outcome timeframe
Days 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours (Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
Results posted on
2015-05-08
Participant Flow
Participant milestones
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
14
|
14
|
12
|
|
Overall Study
COMPLETED
|
13
|
14
|
13
|
12
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
2
|
0
|
1
|
0
|
Baseline Characteristics
Open Label Pharmacokinetic Study of OZ439 and Piperaquine on Administration of OZ439+TPGS Granules for Oral Suspension Alone or With Either Piperaquine Phosphate Tablets or Granules for Oral Solution in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
n=15 Participants
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
n=14 Participants
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
n=14 Participants
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
n=12 Participants
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Total
n=55 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
27.0 years
STANDARD_DEVIATION 9.40 • n=5 Participants
|
31.8 years
STANDARD_DEVIATION 9.70 • n=7 Participants
|
26.9 years
STANDARD_DEVIATION 5.66 • n=5 Participants
|
28.6 years
STANDARD_DEVIATION 9.54 • n=4 Participants
|
28.5 years
STANDARD_DEVIATION 8.71 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
53 Participants
n=21 Participants
|
|
Region of Enrollment
United Kingdom
|
15 participants
n=5 Participants
|
14 participants
n=7 Participants
|
14 participants
n=5 Participants
|
12 participants
n=4 Participants
|
55 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Days 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours (Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.OZ439 observed maximum drug plasma concentration
Outcome measures
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
n=14 Participants
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
n=12 Participants
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
|---|---|---|---|---|
|
OZ439 Cmax
|
1300 ng/mL
Geometric Coefficient of Variation 34.6
|
1490 ng/mL
Geometric Coefficient of Variation 37.9
|
1240 ng/mL
Geometric Coefficient of Variation 29.2
|
1120 ng/mL
Geometric Coefficient of Variation 48.6
|
PRIMARY outcome
Timeframe: Days 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours (Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.OZ439 Area under plasma concentration time curve from time zero extrapolated to infinity.
Outcome measures
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
n=14 Participants
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
n=12 Participants
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
|---|---|---|---|---|
|
OZ439 AUC0-∞
|
15000 ng*h/mL
Geometric Coefficient of Variation 26.3
|
16100 ng*h/mL
Geometric Coefficient of Variation 35.7
|
14100 ng*h/mL
Geometric Coefficient of Variation 35.9
|
13400 ng*h/mL
Geometric Coefficient of Variation 53.7
|
SECONDARY outcome
Timeframe: Days 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours (Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.Piperaquine Observed maximum drug plasma concentration
Outcome measures
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
n=14 Participants
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
|---|---|---|---|---|
|
Piperaquine Cmax
|
249 ng/mL
Geometric Coefficient of Variation 94.3
|
113 ng/mL
Geometric Coefficient of Variation 100.9
|
112 ng/mL
Geometric Coefficient of Variation 68.7
|
—
|
SECONDARY outcome
Timeframe: Days 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours (Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.Piperaquine Area under plasma concentration time curve from time zero extrapolated to infinity.
Outcome measures
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
n=14 Participants
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
n=13 Participants
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
|---|---|---|---|---|
|
Piperaquine AUC0-∞
|
18300 ng*h/mL
Geometric Coefficient of Variation 39.3
|
12400 ng*h/mL
Geometric Coefficient of Variation 43.2
|
12100 ng*h/mL
Geometric Coefficient of Variation 42.1
|
—
|
Adverse Events
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Treatment D: 800mg OZ439 + TPGS
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: 1440mg PQP Tablets & 800mg OZ439 + TPGS
n=15 participants at risk
Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment B: 960mg PQP Tablets & 800mg OZ439 + TPGS
n=14 participants at risk
Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment C: 960mg PQP Granules & 800mg OZ439 + TPGS
n=14 participants at risk
Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
Treatment D: 800mg OZ439 + TPGS
n=12 participants at risk
OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
8.3%
1/12 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Nervous system disorders
Dizziness
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Nausea
|
46.7%
7/15 • Number of events 7 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
21.4%
3/14 • Number of events 3 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
35.7%
5/14 • Number of events 5 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
41.7%
5/12 • Number of events 5 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
14.3%
2/14 • Number of events 2 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
16.7%
2/12 • Number of events 2 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Abdominal distension
|
6.7%
1/15 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
1/15 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
8.3%
1/12 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
8.3%
1/12 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.7%
1/15 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
8.3%
1/12 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
|
General disorders
Feeling Hot
|
0.00%
0/15 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/14 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
7.1%
1/14 • Number of events 1 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
0.00%
0/12 • Up to Day 50 post-dose.
All 55 subjects received one dose of OZ439 alone or in combination with PQP were included in the safety analysis population
|
Additional Information
Dr Thomas Rueckle PhD
Medicines for Malaria Venture (MMV)
Phone: +41 22 799 4567
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee After completion of the study, the Investigator may prepare a joint publication with MMV. The Investigator must undertake not to submit any part of the individual data from this protocol for publication without prior consent of MMV at a mutually agreed time. The confidentiality obligation applies to all personnel involved at the investigational site.
- Publication restrictions are in place
Restriction type: OTHER