Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01075984
Collaborator
(none)
279
5
32.9
Study Details
Study Description
Brief Summary
The purpose of this study is to collect pharmacokinetic (PK) information related to how well intravenous Posaconazole (POS IV), is distributed in the body and to determine the safety and tolerability of this new formulation. In addition, the PK, safety, and tolerability of switching from taking POS IV to taking Posaconazole Oral Suspension (POS Oral) will be evaluated. The data collected in this study will be compared to data collected in previous studies.
Individuals who have been diagnosed by their physicians with a blood disease or cancer that can affect their infection-fighting white blood cells will be asked to participate in the trial. Since these blood diseases and their treatments can weaken the immune system, they may put these individuals at a high risk for getting a serious fungal infection of their internal organs or blood (invasive fungal infection). As these fungal infections can be hard to detect early and can be life-threatening, many physicians believe that individuals diagnosed with these diseases should receive antifungal therapy to try to lower their risk of getting this type of infection.
Enrollment into this study will take place in several stages (cohorts). The determination of which cohort an individual will be asked to participate in is based on which cohort is open at the site at the time the individual is approached to consider study participation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
279 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05520)
Actual Study Start Date
:
Feb 23, 2010
Actual Primary Completion Date
:
Nov 20, 2012
Actual Study Completion Date
:
Nov 20, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: POS IV 200 mg single dose (Cohort 0) POS 200 mg IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) |
Drug: Posaconazole
Other Names:
|
| Placebo Comparator: Dextrose 5% in water (Cohort 0) Placebo IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) |
Drug: Posaconazole
Other Names:
Drug: Dextrose 5% in water
Other Names:
|
| Experimental: POS IV 200 mg BID (Cohort 1) POS 200 mg IV infused over 1.5 hours BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) |
Drug: Posaconazole
Other Names:
|
| Experimental: POS IV 300 mg BID (Cohort 2) POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
Drug: Posaconazole
Other Names:
|
| Experimental: POS IV 300 mg BID (Cohort 3) POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28, or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
Drug: Posaconazole
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Single Dose Trough Concentration of IV Posaconazole (Cmin) [12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Trough Concentration of IV Posaconazole (Cmin) [24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Single Dose Maximum Concentration of IV Posaconazole (Cmax) [Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Maximum Concentration of IV Posaconazole (Cmax) [Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Single Dose Time of Observed Maximum Concentration of IV Posaconazole (Tmax) [Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0 and 1)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Time of Observed Maximum Concentration of IV Posaconazole (Tmax) [Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Single Dose Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC) [Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC) [Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Average Concentration of IV Posaconazole (Cavg) [Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)]
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (24 hours).
- Steady State Total Body Clearance of IV Posaconazole (CL) [Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Trough Concentration of Oral Posaconazole (Cmin) [12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Maximum Concentration of Oral Posaconazole (Cmax) [Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Time of Observed Maximum Concentration of Oral Posaconazole (Tmax) [Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Area Under the Concentration Versus Time Curve of Oral Posaconazole (AUC) [Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
- Steady State Average Concentration of Oral Posaconazole (Cavg) [Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (12 hours).
- Steady State Apparent Total Body Clearance of Oral Posaconazole (CL/F) [Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)]
Blood samples were collected from participants for the determination of plasma POS concentration.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Adult subjects greater than or equal to 18 years of age (weighing greater than 34 kg [75 lb]), of either sex and of any race/ethnicity.
-
Disease definition for each subject: Anticipated (likely to develop within 3 days to 5 days) or documented prolonged neutropenia (absolute neutrophil count [ANC] <500/mm3 [0.5 x 109/L]) at Baseline and likely to last for at least 7 days due to:
-
- Standard intensive chemotherapy, anthracycline-based or other accepted regimen (excluding any investigational agent), for a new diagnosis of acute myelogenous leukemia (AML);
-
- Chemotherapy for AML in first relapse; or
-
- Therapy for myelodysplastic syndromes in transformation to AML or other diagnoses of secondary AML (therapy related, antecedent hematological disorders) or chronic myelogenous leukemia in blast crisis
-
Disease definition for each Cohort 3 subject: In addition to subjects defined above, allogeneic hematopoietic stem cell transplant (HSCT) subjects may be randomized in either the pre-engraftment period (i.e., after they have received their conditioning regimen for the transplant, but while they are still neutropenic) or in the post-engraftment period if they are receiving immunosuppressive therapy for prevention or treatment of graft-versus-host disease (e.g., steroids, tacrolimus, cyclosporin, mycophenolate mofetil, and antithymocyte globulin).
Exclusion Criteria:
-
A female subject must not be pregnant, must not intend to become pregnant during the study, or must not be nursing.
-
Excluded prior treatments. A subject must not have received systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment.
-
A subject must not have moderate or severe liver dysfunction at Baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN. For Cohorts 1 and 2, a subject must not have a known or suspected history of Gilbert's disease.
-
A subject must not have an electrocardiogram (ECG) with a prolonged QTc interval by manual reading: QTc greater than 500 msec.
-
A subject must not have prior enrollment in this study, or other POS studies within 90 days of study entry.
-
A subject must not have a known or suspected invasive or systemic fungal infection at Baseline. Those subjects receiving empiric anti-fungal therapy within 7 days prior to Baseline must have had a diagnostic work-up that ruled out a possible invasive fungal infection.
-
A subject must not have creatinine clearance levels (measured or calculated) below 50 mL/min.
-
A subject must not have a history of Type I hypersensitivity or idiosyncratic reactions to azole agents.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01075984
Other Study ID Numbers:
- P05520
First Posted:
Feb 25, 2010
Last Update Posted:
Nov 13, 2017
Last Verified:
Oct 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Merck Sharp & Dohme LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | All participants who started the study were eligible to enter the follow-up phase, whether or not they completed the treatment phase. |
| Arm/Group Title | Posaconazole (POS) 200 mg IV Single Dose (Cohort 0) | Placebo IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) |
|---|---|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Period Title: Treatment Phase | |||||
| STARTED | 10 | 11 | 21 | 24 | 213 |
| COMPLETED | 10 | 10 | 14 | 17 | 153 |
| NOT COMPLETED | 0 | 1 | 7 | 7 | 60 |
| Period Title: Treatment Phase | |||||
| STARTED | 10 | 10 | 20 | 21 | 212 |
| COMPLETED | 10 | 10 | 19 | 19 | 165 |
| NOT COMPLETED | 0 | 0 | 1 | 2 | 47 |
Baseline Characteristics
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | Placebo IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | Total of all reporting groups |
| Overall Participants | 10 | 11 | 21 | 24 | 213 | 279 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
56.8
(17.4)
|
59.5
(12.3)
|
49.1
(14.7)
|
52.4
(13.4)
|
50.7
(14.7)
|
51.3
(14.7)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
5
50%
|
6
54.5%
|
8
38.1%
|
11
45.8%
|
96
45.1%
|
126
45.2%
|
| Male |
5
50%
|
5
45.5%
|
13
61.9%
|
13
54.2%
|
117
54.9%
|
153
54.8%
|
Outcome Measures
| Title | Single Dose Trough Concentration of IV Posaconazole (Cmin) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 10 | 20 | 22 |
| Mean (Standard Deviation) [ng/mL] |
318
(107)
|
295
(113)
|
467
(172)
|
| Title | Steady State Trough Concentration of IV Posaconazole (Cmin) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. |
| Arm/Group Title | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 19 | 30 |
| Mean (Standard Deviation) [ng/mL] |
958
(605)
|
1046
(515)
|
1164
(462)
|
| Title | Single Dose Maximum Concentration of IV Posaconazole (Cmax) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 10 | 20 | 22 |
| Mean (Standard Deviation) [ng/mL] |
881
(334)
|
990
(467)
|
1590
(980)
|
| Title | Steady State Maximum Concentration of IV Posaconazole (Cmax) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. |
| Arm/Group Title | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 19 | 30 |
| Mean (Standard Deviation) [ng/mL] |
1947
(966)
|
2610
(1010)
|
3696
(2950)
|
| Title | Single Dose Time of Observed Maximum Concentration of IV Posaconazole (Tmax) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0 and 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 10 | 20 | 22 |
| Median (Full Range) [Hours] |
1.42
|
1.48
(50)
|
1.54
|
| Title | Steady State Time of Observed Maximum Concentration of IV Posaconazole (Tmax) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. |
| Arm/Group Title | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 19 | 30 |
| Median (Full Range) [Hours] |
1.00
(50)
|
1.50
(39)
|
1.52
(80)
|
| Title | Single Dose Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 10 | 20 | 22 |
| Mean (Standard Deviation) [hour*ng/mL] |
5940
(2190)
|
5390
(1540)
|
8240
(2140)
|
| Title | Steady State Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. |
| Arm/Group Title | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 19 | 30 |
| Mean (Standard Deviation) [hour*ng/mL] |
28241
(14511)
|
33754
(14196)
|
37586
(11504)
|
| Title | Steady State Average Concentration of IV Posaconazole (Cavg) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (24 hours). |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. |
| Arm/Group Title | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 19 | 30 |
| Mean (Standard Deviation) [ng/mL] |
1180
(605)
|
1410
(592)
|
1566
(479)
|
| Title | Steady State Total Body Clearance of IV Posaconazole (CL) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| CL for posaconazole was not calculated in this study because it was collected in other studies more appropriate for evaluation of this parameter. |
| Arm/Group Title | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) | POS 300 mg IV BID (Cohort 3) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 0 | 0 | 0 |
| Title | Steady State Trough Concentration of Oral Posaconazole (Cmin) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 7 | 4 |
| Mean (Standard Deviation) [ng/mL] |
370
(125)
|
532
(266)
|
316
(164)
|
| Title | Steady State Maximum Concentration of Oral Posaconazole (Cmax) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 7 | 4 |
| Mean (Standard Deviation) [ng/mL] |
494
(176)
|
811
(208)
|
430
(260)
|
| Title | Steady State Time of Observed Maximum Concentration of Oral Posaconazole (Tmax) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 7 | 4 |
| Median (Full Range) [Hours] |
3.03
|
3.05
(50)
|
5.54
(39)
|
| Title | Steady State Area Under the Concentration Versus Time Curve of Oral Posaconazole (AUC) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 7 | 4 |
| Mean (Standard Deviation) [hour*ng/mL] |
5080
(1700)
|
6920
(1910)
|
3970
(2050)
|
| Title | Steady State Average Concentration of Oral Posaconazole (Cavg) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (12 hours). |
| Time Frame | Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure. |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 15 | 7 | 4 |
| Mean (Standard Deviation) [ng/mL] |
423
(144)
|
570
(160)
|
331
(172)
|
| Title | Steady State Apparent Total Body Clearance of Oral Posaconazole (CL/F) |
|---|---|
| Description | Blood samples were collected from participants for the determination of plasma POS concentration. |
| Time Frame | Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| CL/F for posaconazole was not calculated in this study because it was collected in other studies more appropriate for evaluation of this parameter |
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2) |
|---|---|---|---|
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | POS 200 mg IV Single Dose (Cohort 0) | Placebo IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2 and 3) | ||||
| Arm/Group Description | POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) | POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) | POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2); POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. | ||||
All Cause Mortality |
||||||||
| POS 200 mg IV Single Dose (Cohort 0) | Placebo IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2 and 3) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| POS 200 mg IV Single Dose (Cohort 0) | Placebo IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2 and 3) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/10 (20%) | 2/11 (18.2%) | 4/21 (19%) | 71/237 (30%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Agranulocytosis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Anaemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Febrile neutropenia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Thrombocytopenia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Gastrointestinal disorders | ||||||||
| Constipation | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Diarrhoea | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Diarrhoea haemorrhagic | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Intestinal haemorrhage | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Nausea | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Neutropenic colitis | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Vomiting | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| General disorders | ||||||||
| Asthenia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Multi-organ failure | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Pyrexia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 5/237 (2.1%) | 5 |
| Hepatobiliary disorders | ||||||||
| Acute hepatic failure | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Hepatitis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Hyperbilirubinaemia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Immune system disorders | ||||||||
| Graft versus host disease | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Graft versus host disease in intestine | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Graft versus host disease in lung | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Graft versus host disease in skin | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Infections and infestations | ||||||||
| Aspergillosis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 1/237 (0.4%) | 1 |
| Bacteraemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Bacterial sepsis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Bronchopneumonia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Cellulitis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 0/237 (0%) | 0 |
| Cytomegalovirus infection | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Enterococcal bacteraemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Escherichia sepsis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Meningoencephalitis bacterial | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Oral herpes | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Pneumonia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Pulmonary mycosis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Rotavirus infection | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Sepsis | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 5/237 (2.1%) | 5 |
| Septic shock | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Spinal compression fracture | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Splenic rupture | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Subdural haemorrhage | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Transfusion reaction | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Investigations | ||||||||
| Blood bilirubin increased | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 0/237 (0%) | 0 |
| Smear cervix abnormal | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Hypovolaemia | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Pain in extremity | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Rheumatoid arthritis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acute myeloid leukaemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Acute myeloid leukaemia recurrent | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Leukaemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 0/237 (0%) | 0 |
| Myelodysplastic syndrome | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Post transplant lymphoproliferative disorder | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Nervous system disorders | ||||||||
| Cerebral haemorrhage | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Encephalopathy | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Headache | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Myelitis transverse | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Posterior reversible encephalopathy syndrome | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Subarachnoid haemorrhage | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| VIIth nerve paralysis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Renal and urinary disorders | ||||||||
| Renal failure | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 4 |
| Renal failure acute | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute pulmonary oedema | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Acute respiratory distress syndrome | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Acute respiratory failure | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Aspiration | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Dyspnoea | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Pneumothorax | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Pulmonary embolism | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 0/237 (0%) | 0 |
| Pulmonary haemorrhage | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 2/237 (0.8%) | 2 |
| Pulmonary oedema | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Respiratory distress | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Respiratory failure | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Surgical and medical procedures | ||||||||
| Tonsillectomy | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Vascular disorders | ||||||||
| Hypotension | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Venoocclusive disease | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| POS 200 mg IV Single Dose (Cohort 0) | Placebo IV Single Dose (Cohort 0) | POS 200 mg IV BID (Cohort 1) | POS 300 mg IV BID (Cohort 2 and 3) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 11/11 (100%) | 20/21 (95.2%) | 229/237 (96.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 22/237 (9.3%) | 39 |
| Coagulopathy | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Febrile neutropenia | 7/10 (70%) | 9 | 5/11 (45.5%) | 6 | 6/21 (28.6%) | 8 | 52/237 (21.9%) | 66 |
| Leukopenia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 4/237 (1.7%) | 7 |
| Thrombocytopenia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 24/237 (10.1%) | 51 |
| Cardiac disorders | ||||||||
| Angina pectoris | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Atrial flutter | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 3 |
| Sinus tachycardia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Tachycardia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 17/237 (7.2%) | 18 |
| Ear and labyrinth disorders | ||||||||
| Vertigo | 1/10 (10%) | 1 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 15/237 (6.3%) | 18 |
| Eye disorders | ||||||||
| Dry eye | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 3/21 (14.3%) | 3 | 14/237 (5.9%) | 14 |
| Eye haemorrhage | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Ocular hyperaemia | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Visual impairment | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 7/237 (3%) | 7 |
| Abdominal pain | 1/10 (10%) | 1 | 2/11 (18.2%) | 2 | 3/21 (14.3%) | 3 | 41/237 (17.3%) | 46 |
| Abdominal pain lower | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Abdominal pain upper | 3/10 (30%) | 3 | 2/11 (18.2%) | 2 | 2/21 (9.5%) | 4 | 25/237 (10.5%) | 25 |
| Anal fistula | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Aphthous stomatitis | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 3/237 (1.3%) | 3 |
| Constipation | 3/10 (30%) | 3 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 30/237 (12.7%) | 36 |
| Diarrhoea | 2/10 (20%) | 2 | 3/11 (27.3%) | 5 | 6/21 (28.6%) | 18 | 92/237 (38.8%) | 131 |
| Dyspepsia | 1/10 (10%) | 2 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 17/237 (7.2%) | 17 |
| Dysphagia | 2/10 (20%) | 2 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 5/237 (2.1%) | 5 |
| Enteritis | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Flatulence | 1/10 (10%) | 1 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 6/237 (2.5%) | 6 |
| Gastrooesophageal reflux disease | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 7/237 (3%) | 8 |
| Gingival bleeding | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 10/237 (4.2%) | 10 |
| Haematochezia | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Haemorrhoids | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 13/237 (5.5%) | 13 |
| Ileus paralytic | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Mouth haemorrhage | 2/10 (20%) | 2 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 9/237 (3.8%) | 11 |
| Nausea | 2/10 (20%) | 3 | 5/11 (45.5%) | 5 | 9/21 (42.9%) | 10 | 67/237 (28.3%) | 77 |
| Oedema mouth | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 0/237 (0%) | 0 |
| Oral disorder | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 2/237 (0.8%) | 2 |
| Stomatitis | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 15/237 (6.3%) | 15 |
| Tongue coated | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 6/237 (2.5%) | 7 |
| Tongue disorder | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Vomiting | 3/10 (30%) | 4 | 5/11 (45.5%) | 6 | 2/21 (9.5%) | 2 | 42/237 (17.7%) | 48 |
| General disorders | ||||||||
| Catheter site erythema | 0/10 (0%) | 0 | 1/11 (9.1%) | 2 | 2/21 (9.5%) | 3 | 15/237 (6.3%) | 18 |
| Catheter site haematoma | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 0/237 (0%) | 0 |
| Catheter site pain | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 14/237 (5.9%) | 15 |
| Chills | 1/10 (10%) | 1 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 38/237 (16%) | 47 |
| Fatigue | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 24/237 (10.1%) | 25 |
| Infusion site extravasation | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 0/237 (0%) | 0 |
| Injection site inflammation | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Mucosal inflammation | 2/10 (20%) | 2 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 44/237 (18.6%) | 47 |
| Oedema | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 15/237 (6.3%) | 16 |
| Oedema peripheral | 0/10 (0%) | 0 | 3/11 (27.3%) | 3 | 0/21 (0%) | 0 | 35/237 (14.8%) | 39 |
| Pyrexia | 0/10 (0%) | 0 | 3/11 (27.3%) | 4 | 6/21 (28.6%) | 6 | 69/237 (29.1%) | 96 |
| Hepatobiliary disorders | ||||||||
| Cholestasis | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Hyperbilirubinaemia | 2/10 (20%) | 2 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 3/237 (1.3%) | 3 |
| Infections and infestations | ||||||||
| Atypical pneumonia | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Bacteraemia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 3/21 (14.3%) | 3 | 7/237 (3%) | 7 |
| Cellulitis | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 1/237 (0.4%) | 1 |
| Device related infection | 1/10 (10%) | 1 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 6/237 (2.5%) | 7 |
| Enterococcal infection | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 7/237 (3%) | 7 |
| Infection | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 3/237 (1.3%) | 3 |
| Oral herpes | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 3/21 (14.3%) | 3 | 14/237 (5.9%) | 14 |
| Otitis media | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Pneumonia bacterial | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Pseudomonas infection | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Puncture site infection | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Sepsis | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 5/237 (2.1%) | 5 |
| Staphylococcal bacteraemia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 2 | 9/237 (3.8%) | 10 |
| Staphylococcal infection | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 2/21 (9.5%) | 3 | 13/237 (5.5%) | 13 |
| Streptococcal bacteraemia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 2 | 1/237 (0.4%) | 1 |
| Streptococcal infection | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Tonsillitis | 1/10 (10%) | 2 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Urinary tract infection | 1/10 (10%) | 1 | 2/11 (18.2%) | 2 | 0/21 (0%) | 0 | 4/237 (1.7%) | 4 |
| Injury, poisoning and procedural complications | ||||||||
| Transfusion reaction | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 6/237 (2.5%) | 6 |
| Allergic transfusion reaction | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 7/237 (3%) | 7 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 14/237 (5.9%) | 14 |
| Antithrombin III decreased | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Blood creatinine increased | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 12/237 (5.1%) | 12 |
| Weight increased | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 5/237 (2.1%) | 5 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/10 (10%) | 1 | 2/11 (18.2%) | 2 | 1/21 (4.8%) | 1 | 29/237 (12.2%) | 32 |
| Fluid retention | 4/10 (40%) | 4 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 7/237 (3%) | 8 |
| Hyperglycaemia | 0/10 (0%) | 0 | 1/11 (9.1%) | 3 | 2/21 (9.5%) | 2 | 12/237 (5.1%) | 12 |
| Hypoalbuminaemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 3 | 5/237 (2.1%) | 6 |
| Hypocalcaemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 8/237 (3.4%) | 8 |
| Hypokalaemia | 3/10 (30%) | 3 | 2/11 (18.2%) | 2 | 3/21 (14.3%) | 4 | 67/237 (28.3%) | 77 |
| Hypomagnesaemia | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 30/237 (12.7%) | 34 |
| Hyponatraemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 5/237 (2.1%) | 9 |
| Hypophosphataemia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 5 | 21/237 (8.9%) | 24 |
| Hypovolaemia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 10/237 (4.2%) | 10 |
| Back pain | 2/10 (20%) | 2 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 17/237 (7.2%) | 17 |
| Bone pain | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 19/237 (8%) | 21 |
| Flank pain | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 4/237 (1.7%) | 4 |
| Muscle spasms | 2/10 (20%) | 2 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 7/237 (3%) | 7 |
| Pain in extremity | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 10/237 (4.2%) | 10 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Leukaemia | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 0/237 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 16/237 (6.8%) | 20 |
| Dysgeusia | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 14/237 (5.9%) | 14 |
| Headache | 4/10 (40%) | 4 | 1/11 (9.1%) | 1 | 2/21 (9.5%) | 2 | 49/237 (20.7%) | 53 |
| Hypoaesthesia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 2/237 (0.8%) | 2 |
| Paraesthesia | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Sensory loss | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Anxiety | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 13/237 (5.5%) | 14 |
| Confusional state | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 7/237 (3%) | 8 |
| Hallucination | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 4/237 (1.7%) | 4 |
| Insomnia | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 3/21 (14.3%) | 3 | 17/237 (7.2%) | 18 |
| Nervousness | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 1/237 (0.4%) | 1 |
| Renal and urinary disorders | ||||||||
| Urinary retention | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 2/237 (0.8%) | 2 |
| Reproductive system and breast disorders | ||||||||
| Vaginal haemorrhage | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 6/237 (2.5%) | 6 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 6/21 (28.6%) | 6 | 31/237 (13.1%) | 32 |
| Dysphonia | 1/10 (10%) | 1 | 1/11 (9.1%) | 1 | 1/21 (4.8%) | 1 | 1/237 (0.4%) | 1 |
| Dyspnoea | 0/10 (0%) | 0 | 2/11 (18.2%) | 2 | 1/21 (4.8%) | 1 | 23/237 (9.7%) | 26 |
| Epistaxis | 4/10 (40%) | 4 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 40/237 (16.9%) | 52 |
| Oropharyngeal pain | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 1/21 (4.8%) | 1 | 17/237 (7.2%) | 18 |
| Pharyngeal haemorrhage | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Pleuritic pain | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 3/237 (1.3%) | 3 |
| Throat irritation | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 0/237 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Rash | 1/10 (10%) | 1 | 3/11 (27.3%) | 3 | 2/21 (9.5%) | 3 | 56/237 (23.6%) | 71 |
| Swelling face | 1/10 (10%) | 2 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Drug eruption | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 1/237 (0.4%) | 1 |
| Erythema | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 13/237 (5.5%) | 18 |
| Night sweats | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 5/237 (2.1%) | 5 |
| Petechiae | 2/10 (20%) | 3 | 0/11 (0%) | 0 | 0/21 (0%) | 0 | 24/237 (10.1%) | 26 |
| Pruritus | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/21 (9.5%) | 2 | 18/237 (7.6%) | 20 |
| Vascular disorders | ||||||||
| Haematoma | 0/10 (0%) | 0 | 1/11 (9.1%) | 3 | 2/21 (9.5%) | 4 | 12/237 (5.1%) | 15 |
| Hypertension | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/21 (0%) | 0 | 26/237 (11%) | 29 |
| Hypotension | 2/10 (20%) | 2 | 2/11 (18.2%) | 2 | 1/21 (4.8%) | 1 | 14/237 (5.9%) | 16 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts.
Results Point of Contact
| Name/Title | Senior Vice President, Global Cllinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01075984
Other Study ID Numbers:
- P05520
First Posted:
Feb 25, 2010
Last Update Posted:
Nov 13, 2017
Last Verified:
Oct 1, 2017