Trial Outcomes & Findings for Healthy Volunteer Study of the Pharmacokinetics of Oral Piperaquine With OZ439 + TPGS Formulation in the Fasted State (NCT NCT01853475)
NCT ID: NCT01853475
Last Updated: 2015-04-30
Results Overview
OZ439 maximum concentration observed
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Day 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),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
Results posted on
2015-04-30
Participant Flow
Participant milestones
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
7
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
Baseline Characteristics
Healthy Volunteer Study of the Pharmacokinetics of Oral Piperaquine With OZ439 + TPGS Formulation in the Fasted State
Baseline characteristics by cohort
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
n=8 Participants
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
33.5 years
STANDARD_DEVIATION 13.06 • n=5 Participants
|
30.1 years
STANDARD_DEVIATION 6.33 • n=7 Participants
|
30.1 years
STANDARD_DEVIATION 5.79 • n=5 Participants
|
31.3 years
STANDARD_DEVIATION 8.77 • n=4 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
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
8 participants
n=5 Participants
|
24 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 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),168 (Day 8), Day 11, Day 15, Day 29 and Day 43Population: Pharmacokinetic parameters were evaluated using all available concentration data from all 24 subjects who had received at least one treatment of randomised study medication.
OZ439 maximum concentration observed
Outcome measures
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
n=8 Participants
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
|---|---|---|---|
|
OZ439 Cmax
|
1540 ng/mL
Geometric Coefficient of Variation 26.0
|
1360 ng/mL
Geometric Coefficient of Variation 33.8
|
1610 ng/mL
Geometric Coefficient of Variation 37.2
|
PRIMARY outcome
Timeframe: Day 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),168 (Day 8), Day 11, Day 15, Day 29 and Day 43Population: Pharmacokinetic parameters were evaluated using all available concentration data from all 24 subjects who had received at least one treatment of randomised study medication.
Area under the OZ439 plasma concentration time curve from time zero to time infinity using observed values.
Outcome measures
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
n=8 Participants
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
|---|---|---|---|
|
OZ439 AUC0-inf
|
17500 ng*h/mL
Geometric Coefficient of Variation 27.9
|
16000 ng*h/mL
Geometric Coefficient of Variation 24.7
|
18600 ng*h/mL
Geometric Coefficient of Variation 45.4
|
SECONDARY outcome
Timeframe: Day 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),168 (Day 8), Day 11, Day 15, Day 29 and Day 43Population: Pharmacokinetic parameters were evaluated using all available concentration data from all 24 subjects who had received at least one treatment of randomised study medication.
Piperaquine maximum concentration observed
Outcome measures
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
n=8 Participants
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
|---|---|---|---|
|
Piperaquine Cmax
|
202 ng/mL
Geometric Coefficient of Variation 37.6
|
122 ng/mL
Geometric Coefficient of Variation 42.1
|
630 ng/mL
Geometric Coefficient of Variation 54.4
|
SECONDARY outcome
Timeframe: Day 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),168 (Day 8), Day 11, Day 15, Day 29 and Day 43Population: Pharmacokinetic parameters were evaluated using all available concentration data from all 24 subjects who had received at least one treatment of randomised study medication.
Area under the Piperaquine plasma concentration time curve from time zero to time infinity using observed values.
Outcome measures
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
n=8 Participants
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
n=8 Participants
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
|---|---|---|---|
|
Piperaquine AUC0-inf
|
17200 ng*h/mL
Geometric Coefficient of Variation 29.5
|
13400 ng*h/mL
Geometric Coefficient of Variation 23.1
|
29700 ng*h/mL
Geometric Coefficient of Variation 48.0
|
Adverse Events
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Treatment B: PQP 960mg & OZ439+TPGS 800mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment C - PQP 1440mg & OZ439 PIB 800mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: PQP 1440mg & OZ439+TPGS 800mg
n=8 participants at risk
PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment B: PQP 960mg & OZ439+TPGS 800mg
n=8 participants at risk
PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
|
Treatment C - PQP 1440mg & OZ439 PIB 800mg
n=8 participants at risk
PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/8 • Up to Day 43 post-dose.
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Immune system disorders
Seasonal Allergy
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
|
Psychiatric disorders
Nightmare
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
37.5%
3/8 • Number of events 3 • Up to Day 43 post-dose.
|
|
Nervous system disorders
Dizziness
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Gastrointestinal disorders
Nausea
|
50.0%
4/8 • Number of events 4 • Up to Day 43 post-dose.
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/8 • Up to Day 43 post-dose.
|
25.0%
2/8 • Number of events 2 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
2/8 • Number of events 2 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/8 • Up to Day 43 post-dose.
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Gastrointestinal disorders
Change of bowel habit
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Renal and urinary disorders
Urine odour abnormal
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
|
General disorders
Influenza like illness
|
37.5%
3/8 • Number of events 3 • Up to Day 43 post-dose.
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
37.5%
3/8 • Number of events 3 • Up to Day 43 post-dose.
|
|
General disorders
Fatigue
|
12.5%
1/8 • Number of events 1 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
0.00%
0/8 • Up to Day 43 post-dose.
|
Additional Information
Dr Thomas Rueckle
Medicines for Malaria Ventire (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 the Sponsor. The Investigator must undertake not to submit any part of the individual data from this protocol for publication without prior consent of the Sponsor at a mutually agreed time.
- Publication restrictions are in place
Restriction type: OTHER