Trial Outcomes & Findings for Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115) (NCT NCT00686543)
NCT ID: NCT00686543
Last Updated: 2017-04-07
Results Overview
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
75 participants
Primary outcome timeframe
Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8
Results posted on
2017-04-07
Participant Flow
Participant milestones
| Measure |
Not Randomized
Posaconazole oral suspension (POS) 200 mg Three Times a Day (TID) on Days 1-8, administered with food or oral nutritional supplements (participants who discontinued anytime before randomization on Day 8)
|
POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15
POS 200 mg TID on Days 1-8 Followed by POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to continue with POS 200 mg TID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg Twice a Day (BID) on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
14
|
21
|
20
|
20
|
|
Overall Study
COMPLETED
|
0
|
20
|
15
|
17
|
|
Overall Study
NOT COMPLETED
|
14
|
1
|
5
|
3
|
Reasons for withdrawal
| Measure |
Not Randomized
Posaconazole oral suspension (POS) 200 mg Three Times a Day (TID) on Days 1-8, administered with food or oral nutritional supplements (participants who discontinued anytime before randomization on Day 8)
|
POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15
POS 200 mg TID on Days 1-8 Followed by POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to continue with POS 200 mg TID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg Twice a Day (BID) on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
9
|
1
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
0
|
0
|
|
Overall Study
Protocol Violation
|
3
|
0
|
2
|
1
|
Baseline Characteristics
Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
Baseline characteristics by cohort
| Measure |
Not Randomized
n=14 Participants
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who discontinued anytime before randomization on Day 8).
|
POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15
n=21 Participants
POS 200 mg TID on Days 1-8 Followed by POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to continue with POS 200 mg TID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
n=20 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
n=20 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
19 Participants
n=483 Participants
|
62 Participants
n=36 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
13 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
36 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
11 Participants
n=483 Participants
|
39 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Outcome measures
| Measure |
POS 200 mg TID Days 1-8
n=49 Participants
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to one of the three dosing regimens for Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|
|
Mean POS Plasma Concentrations on Days 2, 3, and 8.
Day 2
|
230 ng/mL
Interval 194.0 to 266.0
|
—
|
—
|
|
Mean POS Plasma Concentrations on Days 2, 3, and 8.
Day 3
|
346 ng/mL
Interval 296.0 to 396.0
|
—
|
—
|
|
Mean POS Plasma Concentrations on Days 2, 3, and 8.
Day 8
|
637 ng/mL
Interval 521.0 to 753.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose (0 hour) and 5 hours postdose on Days 8 and 15Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Outcome measures
| Measure |
POS 200 mg TID Days 1-8
n=19 Participants
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to one of the three dosing regimens for Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
n=14 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
n=16 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|
|
Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen
Day 8
|
620 ng/mL
Interval 439.0 to 800.0
|
849 ng/mL
Interval 541.0 to 1156.0
|
473 ng/mL
Interval 361.0 to 585.0
|
|
Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen
Day 15
|
660 ng/mL
Interval 487.0 to 834.0
|
930 ng/mL
Interval 617.0 to 1243.0
|
671 ng/mL
Interval 530.0 to 811.0
|
PRIMARY outcome
Timeframe: Predose (0 hour) and 5 hours postdose on Days 3 and 8Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Outcome measures
| Measure |
POS 200 mg TID Days 1-8
n=49 Participants
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to one of the three dosing regimens for Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Day 3 <250 ng/mL and Day 8 <500 ng/mL
|
17 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Day 3 <250 ng/mL and Day 8 ≥500 ng/mL
|
2 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Total Day 3 <250 ng/mL
|
19 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Day 3 ≥250 ng/mL and Day 8 <500 ng/mL
|
8 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Day 3 ≥250 ng/mL and Day 8 ≥500 ng/mL
|
22 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Total Day 3 ≥250 ng/mL
|
30 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose (0 hour) and 5 hours postdose on Days 3 and 8Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Outcome measures
| Measure |
POS 200 mg TID Days 1-8
n=49 Participants
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to one of the three dosing regimens for Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Day 3 <350 ng/mL and Day 8 <700 ng/mL
|
25 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Day 3 <350 ng/mL and Day 8 ≥700 ng/mL
|
3 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Total Day 3 <350 ng/mL
|
28 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Day 3 ≥350 ng/mL and Day 8 <700 ng/mL
|
7 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Day 3 ≥350 ng/mL and Day 8 ≥700 ng/mL
|
14 Participants
|
—
|
—
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Total Day 3 ≥350 ng/mL
|
21 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose (0 hour) and 5 hours postdose on Days 8 and 15Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
Individual mean concentrations calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Outcome measures
| Measure |
POS 200 mg TID Days 1-8
n=19 Participants
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to one of the three dosing regimens for Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
n=14 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
n=16 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Day 8 <250 ng/mL and Day 15 <500 ng/mL
|
3 Participants
|
3 Participants
|
3 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Day 8 <250 ng/mL and Day 15 ≥500 ng/mL
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Total Day 8 <250 ng/mL
|
5 Participants
|
3 Participants
|
4 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Day 8 ≥250 ng/mL and Day 15 <500 ng/mL
|
6 Participants
|
0 Participants
|
3 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Day 8 ≥250 ng/mL and Day 15 ≥500 ng/mL
|
8 Participants
|
11 Participants
|
9 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Total Day 8 ≥250 ng/mL
|
14 Participants
|
11 Participants
|
12 Participants
|
PRIMARY outcome
Timeframe: Predose (0 hour) and 5 hours postdose on Days 8 and 15Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Outcome measures
| Measure |
POS 200 mg TID Days 1-8
n=19 Participants
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to one of the three dosing regimens for Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
n=14 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
|
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
n=16 Participants
POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).
|
|---|---|---|---|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Day 8 ≥350 ng/mL and Day 15 <700 ng/mL
|
6 Participants
|
2 Participants
|
3 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Day 8 <350 ng/mL and Day 15 <700 ng/mL
|
5 Participants
|
3 Participants
|
5 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Day 8 <350 ng/mL and Day 15 ≥700 ng/mL
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Total Day 8 <350 ng/mL
|
6 Participants
|
3 Participants
|
7 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Day 8 ≥350 ng/mL and Day 15 ≥700 ng/mL
|
7 Participants
|
9 Participants
|
6 Participants
|
|
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Total Day 8 ≥350 ng/mL
|
13 Participants
|
11 Participants
|
9 Participants
|
Adverse Events
POS 200 mg TID on Days 1-8
Serious events: 16 serious events
Other events: 73 other events
Deaths: 0 deaths
POS 200 mg TID on Days 9-15
Serious events: 3 serious events
Other events: 20 other events
Deaths: 0 deaths
POS 400 mg BID on Days 9-15
Serious events: 4 serious events
Other events: 20 other events
Deaths: 0 deaths
POS 400 mg TID on Days 9-15
Serious events: 5 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
POS 200 mg TID on Days 1-8
n=75 participants at risk
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements.
|
POS 200 mg TID on Days 9-15
n=21 participants at risk
POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements.
|
POS 400 mg BID on Days 9-15
n=20 participants at risk
POS 400 mg on Days 9-15, administered with food or oral nutritional supplements.
|
POS 400 mg TID on Days 9-15
n=20 participants at risk
POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Cardiac disorders
Acute coronary syndrome
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/20
|
|
Cardiac disorders
Bradycardia
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Cardiac disorders
Cardiac arrest
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/20
|
|
Cardiac disorders
Cardiac failure congestive
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Cardiac disorders
Cardiomyopathy
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/20
|
|
Cardiac disorders
Tachycardia
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/20
|
|
General disorders
Chills
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
General disorders
Pyrexia
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Hepatobiliary disorders
Cholecystitis acute
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Immune system disorders
Acute graft versus host disease in liver
|
1.3%
1/75 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Infections and infestations
Bacteraemia
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Meningitis
|
1.3%
1/75 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Infections and infestations
Pneumonia
|
5.3%
4/75 • Number of events 4
|
9.5%
2/21 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Infections and infestations
Sepsis
|
4.0%
3/75 • Number of events 3
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Systemic candida
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/20
|
|
Investigations
Transaminases increased
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
1.3%
1/75 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
1.3%
1/75 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Nervous system disorders
Cranial neuropathy
|
1.3%
1/75 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Nervous system disorders
Somnolence
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/20
|
|
Psychiatric disorders
Mental status changes
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.7%
2/75 • Number of events 2
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal discomfort
|
1.3%
1/75 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.7%
2/75 • Number of events 2
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Vascular disorders
Deep vein thrombosis
|
1.3%
1/75 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal hypoaesthesia
|
1.3%
1/75 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
Other adverse events
| Measure |
POS 200 mg TID on Days 1-8
n=75 participants at risk
POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements.
|
POS 200 mg TID on Days 9-15
n=21 participants at risk
POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements.
|
POS 400 mg BID on Days 9-15
n=20 participants at risk
POS 400 mg on Days 9-15, administered with food or oral nutritional supplements.
|
POS 400 mg TID on Days 9-15
n=20 participants at risk
POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.7%
2/75 • Number of events 2
|
0.00%
0/21
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Blood and lymphatic system disorders
Coagulopathy
|
4.0%
3/75 • Number of events 4
|
0.00%
0/21
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
21.3%
16/75 • Number of events 17
|
23.8%
5/21 • Number of events 5
|
25.0%
5/20 • Number of events 6
|
20.0%
4/20 • Number of events 4
|
|
Cardiac disorders
Tachycardia
|
5.3%
4/75 • Number of events 5
|
0.00%
0/21
|
15.0%
3/20 • Number of events 4
|
5.0%
1/20 • Number of events 1
|
|
Ear and labyrinth disorders
Vertigo
|
9.3%
7/75 • Number of events 9
|
14.3%
3/21 • Number of events 4
|
5.0%
1/20 • Number of events 1
|
15.0%
3/20 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.3%
4/75 • Number of events 6
|
0.00%
0/21
|
10.0%
2/20 • Number of events 4
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
5.3%
4/75 • Number of events 4
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
16.0%
12/75 • Number of events 16
|
19.0%
4/21 • Number of events 7
|
20.0%
4/20 • Number of events 5
|
15.0%
3/20 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
5/75 • Number of events 5
|
9.5%
2/21 • Number of events 2
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
20.0%
15/75 • Number of events 16
|
19.0%
4/21 • Number of events 4
|
30.0%
6/20 • Number of events 6
|
20.0%
4/20 • Number of events 5
|
|
Gastrointestinal disorders
Diarrhoea
|
52.0%
39/75 • Number of events 83
|
47.6%
10/21 • Number of events 27
|
45.0%
9/20 • Number of events 20
|
65.0%
13/20 • Number of events 23
|
|
Gastrointestinal disorders
Dry mouth
|
2.7%
2/75 • Number of events 2
|
0.00%
0/21
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Dyspepsia
|
10.7%
8/75 • Number of events 11
|
19.0%
4/21 • Number of events 6
|
10.0%
2/20 • Number of events 3
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Flatulence
|
14.7%
11/75 • Number of events 15
|
9.5%
2/21 • Number of events 4
|
25.0%
5/20 • Number of events 7
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
4.0%
3/75 • Number of events 3
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Haemorrhoids
|
12.0%
9/75 • Number of events 12
|
19.0%
4/21 • Number of events 4
|
20.0%
4/20 • Number of events 7
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
52.0%
39/75 • Number of events 67
|
52.4%
11/21 • Number of events 17
|
50.0%
10/20 • Number of events 14
|
60.0%
12/20 • Number of events 27
|
|
Gastrointestinal disorders
Odynophagia
|
2.7%
2/75 • Number of events 2
|
0.00%
0/21
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Oral pain
|
6.7%
5/75 • Number of events 5
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Stomatitis
|
18.7%
14/75 • Number of events 18
|
14.3%
3/21 • Number of events 3
|
15.0%
3/20 • Number of events 3
|
25.0%
5/20 • Number of events 9
|
|
Gastrointestinal disorders
Vomiting
|
29.3%
22/75 • Number of events 29
|
28.6%
6/21 • Number of events 10
|
25.0%
5/20 • Number of events 5
|
35.0%
7/20 • Number of events 9
|
|
General disorders
Catheter site erythema
|
5.3%
4/75 • Number of events 4
|
4.8%
1/21 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Chest pain
|
6.7%
5/75 • Number of events 5
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
10.0%
2/20 • Number of events 2
|
|
General disorders
Chills
|
18.7%
14/75 • Number of events 15
|
14.3%
3/21 • Number of events 4
|
15.0%
3/20 • Number of events 3
|
40.0%
8/20 • Number of events 8
|
|
General disorders
Mucosal inflammation
|
26.7%
20/75 • Number of events 30
|
33.3%
7/21 • Number of events 9
|
25.0%
5/20 • Number of events 6
|
20.0%
4/20 • Number of events 10
|
|
General disorders
Oedema peripheral
|
5.3%
4/75 • Number of events 4
|
4.8%
1/21 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Pyrexia
|
44.0%
33/75 • Number of events 40
|
47.6%
10/21 • Number of events 13
|
55.0%
11/20 • Number of events 13
|
50.0%
10/20 • Number of events 12
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
5.3%
4/75 • Number of events 17
|
0.00%
0/21
|
5.0%
1/20 • Number of events 3
|
10.0%
2/20 • Number of events 12
|
|
Immune system disorders
Drug hypersensitivity
|
4.0%
3/75 • Number of events 3
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Infections and infestations
Clostridial infection
|
5.3%
4/75 • Number of events 4
|
4.8%
1/21 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
|
Infections and infestations
Clostridium difficile colitis
|
2.7%
2/75 • Number of events 2
|
9.5%
2/21 • Number of events 2
|
0.00%
0/20
|
0.00%
0/20
|
|
Infections and infestations
Escherichia bacteraemia
|
4.0%
3/75 • Number of events 3
|
9.5%
2/21 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Infections and infestations
Herpes simplex
|
5.3%
4/75 • Number of events 5
|
9.5%
2/21 • Number of events 3
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Infections and infestations
Infection
|
14.7%
11/75 • Number of events 11
|
19.0%
4/21 • Number of events 4
|
20.0%
4/20 • Number of events 4
|
15.0%
3/20 • Number of events 3
|
|
Investigations
C-reactive protein increased
|
2.7%
2/75 • Number of events 2
|
0.00%
0/21
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Investigations
Transaminases increased
|
4.0%
3/75 • Number of events 4
|
0.00%
0/21
|
0.00%
0/20
|
15.0%
3/20 • Number of events 4
|
|
Metabolism and nutrition disorders
Anorexia
|
16.0%
12/75 • Number of events 14
|
4.8%
1/21 • Number of events 1
|
20.0%
4/20 • Number of events 6
|
25.0%
5/20 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
25.3%
19/75 • Number of events 24
|
14.3%
3/21 • Number of events 4
|
25.0%
5/20 • Number of events 6
|
50.0%
10/20 • Number of events 13
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
8.0%
6/75 • Number of events 6
|
4.8%
1/21 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
20.0%
4/20 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
5/75 • Number of events 5
|
4.8%
1/21 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
12.0%
9/75 • Number of events 9
|
14.3%
3/21 • Number of events 3
|
10.0%
2/20 • Number of events 2
|
10.0%
2/20 • Number of events 2
|
|
Nervous system disorders
Headache
|
5.3%
4/75 • Number of events 7
|
0.00%
0/21
|
10.0%
2/20 • Number of events 3
|
10.0%
2/20 • Number of events 4
|
|
Nervous system disorders
Paraesthesia
|
2.7%
2/75 • Number of events 2
|
9.5%
2/21 • Number of events 2
|
0.00%
0/20
|
0.00%
0/20
|
|
Psychiatric disorders
Agitation
|
5.3%
4/75 • Number of events 5
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
4.0%
3/75 • Number of events 3
|
9.5%
2/21 • Number of events 2
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
2.7%
2/75 • Number of events 2
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
0.00%
0/20
|
|
Psychiatric disorders
Insomnia
|
8.0%
6/75 • Number of events 6
|
4.8%
1/21 • Number of events 1
|
15.0%
3/20 • Number of events 3
|
5.0%
1/20 • Number of events 1
|
|
Psychiatric disorders
Sleep disorder
|
4.0%
3/75 • Number of events 3
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.0%
6/75 • Number of events 9
|
14.3%
3/21 • Number of events 3
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.3%
7/75 • Number of events 7
|
9.5%
2/21 • Number of events 2
|
15.0%
3/20 • Number of events 3
|
10.0%
2/20 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.3%
7/75 • Number of events 10
|
4.8%
1/21 • Number of events 1
|
15.0%
3/20 • Number of events 3
|
10.0%
2/20 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.0%
9/75 • Number of events 11
|
9.5%
2/21 • Number of events 3
|
10.0%
2/20 • Number of events 2
|
25.0%
5/20 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.3%
4/75 • Number of events 4
|
4.8%
1/21 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.3%
7/75 • Number of events 8
|
14.3%
3/21 • Number of events 3
|
15.0%
3/20 • Number of events 3
|
5.0%
1/20 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
15/75 • Number of events 15
|
23.8%
5/21 • Number of events 5
|
30.0%
6/20 • Number of events 6
|
15.0%
3/20 • Number of events 3
|
|
Vascular disorders
Hypertension
|
4.0%
3/75 • Number of events 3
|
0.00%
0/21
|
15.0%
3/20 • Number of events 3
|
0.00%
0/20
|
|
Vascular disorders
Hypotension
|
12.0%
9/75 • Number of events 12
|
0.00%
0/21
|
20.0%
4/20 • Number of events 6
|
15.0%
3/20 • Number of events 3
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor and investigator will publish/present study results together with other study sites, unless written permission is obtained. The investigator provides to the sponsor 45 days prior to submission for publication/presentation, copies of abstracts or manuscripts reporting any study results. The sponsor has the right to review/comment on the data analysis and presentation regarding proprietary information, accuracy and fair blance of the information, and compliance with FDA regulations.
- Publication restrictions are in place
Restriction type: OTHER