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A Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children (P03579)

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ClinicalTrials.gov Identifier: NCT01716234
Recruitment Status : Terminated (Study was terminated early (10 July 2015) based on preliminary analysis of pharmacokinetic data.)
First Posted : October 29, 2012
Results First Posted : April 15, 2016
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fungal Infections
Interventions Drug: Posaconazole 12 mg/kg/day BID
Drug: Posaconazole 18 mg/kg/day BID
Drug: Posaconazole 18 mg/kg/day TID
Drug: Posaconazole 12 mg/kg/day TID
Enrollment 142

Recruitment Details  
Pre-assignment Details A total of 160 participants were screened, 142 were randomized / enrolled, and 136 were treated. An arm planned for participants aged 3 months to <2 years to receive posaconazole 18 mg/kg/day TID was never initiated.
Arm/Group Title POS 12 BID 2 to <7 Years POS 12 BID 7 to <18 Years POS 18 BID 2 to <7 Years POS 18 BID 7 to <18 Years POS 18 TID 2 to <7 Years POS 18 TID 7 to <18 Years POS 12 TID 3 Months to <2 Years
Hide Arm/Group Description Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days. Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Period Title: Overall Study
Started 24 22 20 28 15 32 1
Treated 22 21 19 28 15 30 1
Completed 14 12 15 16 10 18 1
Not Completed 10 10 5 12 5 14 0
Reason Not Completed
Protocol Violation             0             0             0             1             1             1             0
Lack of Efficacy             0             0             0             1             0             0             0
Did not meet protocol eligibility             0             0             1             0             0             4             0
Adverse Event             7             10             2             8             3             6             0
Withdrawal by Subject             3             0             2             2             1             3             0
Arm/Group Title POS 12 BID 2 to <7 Years POS 12 BID 7 to <18 Years POS 18 BID 2 to <7 Years POS 18 BID 7 to <18 Years POS 18 TID 2 to <7 Years POS 18 TID 7 to <18 Years POS 12 TID 3 Months to <2 Years Total
Hide Arm/Group Description Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days. Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days. Total of all reporting groups
Overall Number of Baseline Participants 24 22 20 28 15 32 1 142
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 22 participants 20 participants 28 participants 15 participants 32 participants 1 participants 142 participants
4.0  (1.3) 11.9  (3.5) 4.4  (1.5) 12.2  (3.2) 4.1  (1.3) 13.1  (3.0) 0.9  (0) 8.9  (4.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 20 participants 28 participants 15 participants 32 participants 1 participants 142 participants
Female
10
  41.7%
12
  54.5%
8
  40.0%
9
  32.1%
6
  40.0%
14
  43.8%
0
   0.0%
59
  41.5%
Male
14
  58.3%
10
  45.5%
12
  60.0%
19
  67.9%
9
  60.0%
18
  56.3%
1
 100.0%
83
  58.5%
1.Primary Outcome
Title Average Concentration of Posaconazole (Cavg) on Day 1 (Single Dose)
Hide Description Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 1. The 12-hour sample was not obtained for the TID dose groups. Day 1 pharmacokinetic samples were not collected for participants 3 months to <2 years of age weighing <6.5 kg.
Time Frame Up to 12 hours after the first dose (BID dose groups) or up to 8 hours after the first dose (TID dose (TID dose groups)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic evaluable population included all treated participants with evaluable samples applicable to the endpoint.
Arm/Group Title POS 12 BID 2 to <7 Years POS 12 BID 7 to <18 Years POS 18 BID 2 to <7 Years POS 18 BID 7 to <18 Years POS 18 TID 2 to <7 Years POS 18 TID 7 to <18 Years POS 12 TID 3 Months to <2 Years
Hide Arm/Group Description:
Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Overall Number of Participants Analyzed 22 19 12 12 5 10 1
Mean (Standard Deviation)
Unit of Measure: ng/mL
122  (101) 107  (92.5) 112  (86.9) 113  (100) 68.4  (40.4) 57.9  (30.2) 68.5  (0)
2.Primary Outcome
Title Average Concentration of Posaconazole (Cavg) on Day 7 (Steady State)
Hide Description Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 7 (steady state). The 12-hour sample was not obtained for the TID dose groups. The target Cavg range was 500 to <2500 ng/mL.
Time Frame Up to 12 hours after the first dose on Day 7 (BID dose groups) or up to 8 hours after the first dose on Day 7 (TID dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic evaluable population included all treated participants with evaluable samples applicable to the endpoint.
Arm/Group Title POS 12 BID 2 to <7 Years POS 12 BID 7 to <18 Years POS 18 BID 2 to <7 Years POS 18 BID 7 to <18 Years POS 18 TID 2 to <7 Years POS 18 TID 7 to <18 Years POS 12 TID 3 Months to <2 Years
Hide Arm/Group Description:
Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Overall Number of Participants Analyzed 16 14 12 12 5 10 1
Mean (Standard Deviation)
Unit of Measure: ng/mL
604  (779) 1050  (789) 485  (306) 1240  (1400) 620  (411) 1150  (750) 453  (0)
3.Secondary Outcome
Title Number of Participants With an Adverse Event
Hide Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.
Time Frame Up to Day 58
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed was all treated participants.
Arm/Group Title POS 12 BID 2 to <7 Years POS 12 BID 7 to <18 Years POS 18 BID 2 to <7 Years POS 18 BID 7 to <18 Years POS 18 TID 2 to <7 Years POS 18 TID 7 to <18 Years POS 12 TID 3 Months to <2 Years
Hide Arm/Group Description:
Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Overall Number of Participants Analyzed 22 21 19 28 15 30 1
Measure Type: Number
Unit of Measure: Participants
21 21 16 26 13 30 1
4.Secondary Outcome
Title Number of Participants With an Adverse Event Leading to Study Drug Discontinuation
Hide Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.
Time Frame Up to Day 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed was all treated participants.
Arm/Group Title POS 12 BID 2 to <7 Years POS 12 BID 7 to <18 Years POS 18 BID 2 to <7 Years POS 18 BID 7 to <18 Years POS 18 TID 2 to <7 Years POS 18 TID 7 to <18 Years POS 12 TID 3 Months to <2 Years
Hide Arm/Group Description:
Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Overall Number of Participants Analyzed 22 21 19 28 15 30 1
Measure Type: Number
Unit of Measure: Participants
7 9 2 9 3 6 0
Time Frame All AEs: from Day 1 up to Day 39; SAEs: up to Day 58.
Adverse Event Reporting Description The population analyzed is all treated participants.
 
Arm/Group Title POS 12 BID 2 to <7 Yrs POS 12 BID 7 to <18 Yrs POS 18 BID 2 to <7 Yrs POS 18 BID 7 to <18 Yrs POS 18 TID 2 to <7 Yrs POS 18 TID 7 to <18 Yrs POS 12 TID 3 Months to <2 Yrs
Hide Arm/Group Description Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days. Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days. Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days. Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
All-Cause Mortality
POS 12 BID 2 to <7 Yrs POS 12 BID 7 to <18 Yrs POS 18 BID 2 to <7 Yrs POS 18 BID 7 to <18 Yrs POS 18 TID 2 to <7 Yrs POS 18 TID 7 to <18 Yrs POS 12 TID 3 Months to <2 Yrs
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
POS 12 BID 2 to <7 Yrs POS 12 BID 7 to <18 Yrs POS 18 BID 2 to <7 Yrs POS 18 BID 7 to <18 Yrs POS 18 TID 2 to <7 Yrs POS 18 TID 7 to <18 Yrs POS 12 TID 3 Months to <2 Yrs
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/22 (22.73%)      3/21 (14.29%)      1/19 (5.26%)      7/28 (25.00%)      7/15 (46.67%)      11/30 (36.67%)      1/1 (100.00%)    
Blood and lymphatic system disorders               
Anaemia  1  1/22 (4.55%)  1 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Febrile neutropenia  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 3/28 (10.71%)  3 5/15 (33.33%)  7 5/30 (16.67%)  5 1/1 (100.00%)  2
Neutropenia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Thrombocytopenia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Cardiac disorders               
Bradycardia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Gastrointestinal disorders               
Nausea  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
General disorders               
Hypothermia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Mucosal inflammation  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Multi-organ failure  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Pyrexia  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Hepatobiliary disorders               
Hepatic haemorrhage  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Hepatic vein occlusion  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Hepatobiliary disease  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Venoocclusive liver disease  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Immune system disorders               
Anaphylactic reaction  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Infections and infestations               
Catheter site cellulitis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Pneumonia klebsiella  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Puncture site infection  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Sepsis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Streptococcal bacteraemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Investigations               
Alanine aminotransferase increased  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Aspartate aminotransferase increased  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Chemotherapeutic drug level increased  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Electrocardiogram T wave inversion  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Transaminases increased  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Burkitt's lymphoma recurrent  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Nervous system disorders               
Headache  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Seizure  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Renal and urinary disorders               
Acute kidney injury  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Renal failure  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Reproductive system and breast disorders               
Menorrhagia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Acute respiratory distress syndrome  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Epistaxis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Respiratory failure  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Skin and subcutaneous tissue disorders               
Skin lesion  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Vascular disorders               
Hypotension  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
POS 12 BID 2 to <7 Yrs POS 12 BID 7 to <18 Yrs POS 18 BID 2 to <7 Yrs POS 18 BID 7 to <18 Yrs POS 18 TID 2 to <7 Yrs POS 18 TID 7 to <18 Yrs POS 12 TID 3 Months to <2 Yrs
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/22 (95.45%)      20/21 (95.24%)      16/19 (84.21%)      26/28 (92.86%)      13/15 (86.67%)      28/30 (93.33%)      1/1 (100.00%)    
Blood and lymphatic system disorders               
Anaemia  1  4/22 (18.18%)  6 2/21 (9.52%)  3 3/19 (15.79%)  6 8/28 (28.57%)  12 3/15 (20.00%)  11 6/30 (20.00%)  12 0/1 (0.00%)  0
Coagulopathy  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 2/28 (7.14%)  2 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Febrile neutropenia  1  1/22 (4.55%)  1 4/21 (19.05%)  4 0/19 (0.00%)  0 4/28 (14.29%)  4 4/15 (26.67%)  5 5/30 (16.67%)  5 0/1 (0.00%)  0
Leukopenia  1  5/22 (22.73%)  5 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Lymphopenia  1  2/22 (9.09%)  2 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Neutropenia  1  3/4 (75.00%)  3 0/21 (0.00%)  0 1/19 (5.26%)  1 2/28 (7.14%)  2 1/15 (6.67%)  1 2/30 (6.67%)  2 0/1 (0.00%)  0
Thrombocytopenia  1  8/22 (36.36%)  19 7/21 (33.33%)  15 3/19 (15.79%)  10 6/28 (21.43%)  22 1/15 (6.67%)  2 5/30 (16.67%)  8 0/1 (0.00%)  0
Cardiac disorders               
Bradycardia  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Sinus tachycardia  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 2/15 (13.33%)  2 1/30 (3.33%)  2 0/1 (0.00%)  0
Tachycardia  1  3/22 (13.64%)  3 2/21 (9.52%)  2 1/19 (5.26%)  1 2/28 (7.14%)  2 1/15 (6.67%)  1 3/30 (10.00%)  4 0/1 (0.00%)  0
Congenital, familial and genetic disorders               
Antithrombin III deficiency  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Ear and labyrinth disorders               
Ear pain  1  1/22 (4.55%)  1 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Eye disorders               
Conjunctival hyperaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Dry eye  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Eye movement disorder  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Eye pruritus  1  1/22 (4.55%)  1 0/21 (0.00%)  0 2/19 (10.53%)  2 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Eye swelling  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Eyelid oedema  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Photophobia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Gastrointestinal disorders               
Abdominal pain  1  7/22 (31.82%)  7 6/21 (28.57%)  7 1/19 (5.26%)  1 2/28 (7.14%)  2 3/15 (20.00%)  3 4/30 (13.33%)  5 0/1 (0.00%)  0
Abdominal pain upper  1  2/22 (9.09%)  2 0/21 (0.00%)  0 1/19 (5.26%)  1 1/28 (3.57%)  1 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Ascites  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  2 0/30 (0.00%)  0 0/1 (0.00%)  0
Constipation  1  0/22 (0.00%)  0 4/21 (19.05%)  4 1/19 (5.26%)  1 1/28 (3.57%)  1 1/15 (6.67%)  1 4/30 (13.33%)  5 0/1 (0.00%)  0
Diarrhoea  1  5/22 (22.73%)  5 3/21 (14.29%)  3 3/19 (15.79%)  5 7/28 (25.00%)  7 3/15 (20.00%)  7 5/30 (16.67%)  5 0/1 (0.00%)  0
Dyspepsia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Frequent bowel movements  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Gingival pain  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Lip dry  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 3/30 (10.00%)  3 0/1 (0.00%)  0
Loose tooth  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Nausea  1  5/22 (22.73%)  8 3/21 (14.29%)  3 2/19 (10.53%)  5 9/28 (32.14%)  9 3/15 (20.00%)  3 13/30 (43.33%)  21 0/1 (0.00%)  0
Oral pain  1  0/22 (0.00%)  0 2/21 (9.52%)  2 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  2 0/1 (0.00%)  0
Proctitis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Retching  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Stomatitis  1  3/22 (13.64%)  4 0/21 (0.00%)  0 2/19 (10.53%)  2 4/28 (14.29%)  5 5/15 (33.33%)  9 6/30 (20.00%)  8 0/1 (0.00%)  0
Tongue coated  1  1/22 (4.55%)  1 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Vomiting  1  8/22 (36.36%)  13 3/21 (14.29%)  5 5/19 (26.32%)  6 11/28 (39.29%)  14 7/15 (46.67%)  11 9/30 (30.00%)  14 0/1 (0.00%)  0
Abdominal distension  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Enteritis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Proctalgia  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
General disorders               
Catheter site erythema  1  2/22 (9.09%)  2 1/21 (4.76%)  1 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Catheter site pruritus  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Chills  1  1/22 (4.55%)  1 1/21 (4.76%)  1 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 3/30 (10.00%)  3 0/1 (0.00%)  0
Device occlusion  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/19 (0.00%)  0 2/28 (7.14%)  3 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Fatigue  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 3/28 (10.71%)  3 0/15 (0.00%)  0 6/30 (20.00%)  7 0/1 (0.00%)  0
Mucosal inflammation  1  9/22 (40.91%)  9 3/21 (14.29%)  3 2/19 (10.53%)  5 7/28 (25.00%)  7 1/15 (6.67%)  1 4/30 (13.33%)  4 0/1 (0.00%)  0
Oedema  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 2/28 (7.14%)  2 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Pain  1  0/22 (0.00%)  0 0/21 (0.00%)  0 2/19 (10.53%)  3 1/28 (3.57%)  1 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Pyrexia  1  13/22 (59.09%)  14 8/21 (38.10%)  9 3/19 (15.79%)  3 8/28 (28.57%)  10 2/15 (13.33%)  4 6/30 (20.00%)  7 0/1 (0.00%)  0
Vessel puncture site pain  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Local swelling  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Oedema peripheral  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/19 (5.26%)  1 1/28 (3.57%)  1 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Immune system disorders               
Engraftment syndrome  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Graft versus host disease in skin  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Infections and infestations               
Alpha haemolytic streptococcal infection  1  0/22 (0.00%)  0 2/21 (9.52%)  2 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Bacteraemia  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/19 (0.00%)  0 1/28 (3.57%)  1 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Gingivitis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 2/15 (13.33%)  2 0/30 (0.00%)  0 0/1 (0.00%)  0
Infection  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Pseudomonal bacteraemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Respiratory tract infection  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 1/1 (100.00%)  1
Rhinitis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 2/19 (10.53%)  3 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Viral infection  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Vulvitis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Cellulitis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Clostridium difficile infection  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Cystitis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Sinusitis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Streptococcal infection  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Viraemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Injury, poisoning and procedural complications               
Allergic transfusion reaction  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 2/28 (7.14%)  2 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Infusion related reaction  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Procedural headache  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Transfusion reaction  1  1/22 (4.55%)  1 1/21 (4.76%)  1 0/19 (0.00%)  0 2/28 (7.14%)  2 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Contusion  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 1/30 (3.33%)  2 0/1 (0.00%)  0
Fall  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Skin abrasion  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Investigations               
Alanine aminotransferase increased  1  1/22 (4.55%)  1 1/21 (4.76%)  1 1/19 (5.26%)  1 3/28 (10.71%)  3 2/15 (13.33%)  5 2/30 (6.67%)  2 0/1 (0.00%)  0
Aspartate aminotransferase increased  1  0/22 (0.00%)  0 1/21 (4.76%)  1 1/19 (5.26%)  1 1/28 (3.57%)  1 2/15 (13.33%)  5 1/30 (3.33%)  1 0/1 (0.00%)  0
Biopsy skin  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Blood bilirubin increased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  4 0/30 (0.00%)  0 0/1 (0.00%)  0
Electrocardiogram QT prolonged  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 2/28 (7.14%)  2 1/15 (6.67%)  1 2/30 (6.67%)  3 0/1 (0.00%)  0
Fluid balance positive  1  1/22 (4.55%)  1 3/21 (14.29%)  5 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
International normalised ratio decreased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Lymphocyte count decreased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 2/30 (6.67%)  5 0/1 (0.00%)  0
Neutrophil count decreased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  2 1/28 (3.57%)  1 1/15 (6.67%)  3 2/30 (6.67%)  4 0/1 (0.00%)  0
Platelet count decreased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 2/19 (10.53%)  11 1/28 (3.57%)  1 2/15 (13.33%)  5 4/30 (13.33%)  11 0/1 (0.00%)  0
Transaminases increased  1  2/22 (9.09%)  2 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
White blood cell count decreased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  3 0/28 (0.00%)  0 1/15 (6.67%)  3 3/30 (10.00%)  4 0/1 (0.00%)  0
Blood glucose increased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Gamma-glutamyltransferase increased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 1/28 (3.57%)  1 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Weight increased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Metabolism and nutrition disorders               
Decreased appetite  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 3/15 (20.00%)  3 8/30 (26.67%)  9 0/1 (0.00%)  0
Fluid overload  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 2/30 (6.67%)  2 0/1 (0.00%)  0
Hyperalbuminaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  2 0/30 (0.00%)  0 0/1 (0.00%)  0
Hyperglycaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 2/15 (13.33%)  4 3/30 (10.00%)  3 0/1 (0.00%)  0
Hypertriglyceridaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 1/15 (6.67%)  2 0/30 (0.00%)  0 0/1 (0.00%)  0
Hypoalbuminaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 2/15 (13.33%)  4 1/30 (3.33%)  1 0/1 (0.00%)  0
Hypocalcaemia  1  0/22 (0.00%)  0 1/21 (4.76%)  2 0/19 (0.00%)  0 1/28 (3.57%)  1 1/15 (6.67%)  3 0/30 (0.00%)  0 0/1 (0.00%)  0
Hypoglycaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Hypokalaemia  1  2/22 (9.09%)  2 3/21 (14.29%)  6 1/19 (5.26%)  1 1/28 (3.57%)  2 4/15 (26.67%)  6 2/30 (6.67%)  3 0/1 (0.00%)  0
Hypomagnesaemia  1  1/22 (4.55%)  1 4/21 (19.05%)  4 0/19 (0.00%)  0 1/28 (3.57%)  2 0/15 (0.00%)  0 2/30 (6.67%)  3 0/1 (0.00%)  0
Hyponatraemia  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Hypophosphataemia  1  2/22 (9.09%)  2 2/21 (9.52%)  2 0/19 (0.00%)  0 1/28 (3.57%)  1 2/15 (13.33%)  3 0/30 (0.00%)  0 0/1 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Back pain  1  1/22 (4.55%)  1 2/21 (9.52%)  2 1/19 (5.26%)  1 1/28 (3.57%)  1 0/15 (0.00%)  0 1/30 (3.33%)  1 0/1 (0.00%)  0
Bone pain  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Pain in extremity  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 2/15 (13.33%)  2 3/30 (10.00%)  4 0/1 (0.00%)  0
Nervous system disorders               
Dizziness  1  0/22 (0.00%)  0 2/21 (9.52%)  2 0/19 (0.00%)  0 1/28 (3.57%)  1 0/15 (0.00%)  0 4/30 (13.33%)  4 0/1 (0.00%)  0
Dysgeusia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Headache  1  1/22 (4.55%)  1 2/21 (9.52%)  2 1/19 (5.26%)  1 8/28 (28.57%)  10 1/15 (6.67%)  1 3/30 (10.00%)  3 0/1 (0.00%)  0
Psychiatric disorders               
Abnormal behavior  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Agitation  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Hallucination  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Insomnia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Renal and urinary disorders               
Dysuria  1  0/22 (0.00%)  0 1/21 (4.76%)  2 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Proteinuria  1  1/22 (4.55%)  1 2/21 (9.52%)  2 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Reproductive system and breast disorders               
Genital pain  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Genital rash  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Pruritus genital  1  2/22 (9.09%)  2 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Genital ulceration  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Penile oedema  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Cough  1  2/22 (9.09%)  2 3/21 (14.29%)  3 3/19 (15.79%)  3 1/28 (3.57%)  1 2/15 (13.33%)  2 2/30 (6.67%)  2 0/1 (0.00%)  0
Epistaxis  1  1/22 (4.55%)  1 1/21 (4.76%)  1 0/19 (0.00%)  0 2/28 (7.14%)  3 1/15 (6.67%)  1 3/30 (10.00%)  4 0/1 (0.00%)  0
Hypoxia  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Oropharyngeal pain  1  1/22 (4.55%)  2 0/21 (0.00%)  0 1/19 (5.26%)  1 2/28 (7.14%)  2 1/15 (6.67%)  1 4/30 (13.33%)  4 0/1 (0.00%)  0
Tachypnoea  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 2/28 (7.14%)  2 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Nasal congestion  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Pleural effusion  1  0/22 (0.00%)  0 1/21 (4.76%)  1 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Skin and subcutaneous tissue disorders               
Alopecia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 1/15 (6.67%)  1 1/30 (3.33%)  1 0/1 (0.00%)  0
Dermatitis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/19 (5.26%)  3 1/28 (3.57%)  1 2/15 (13.33%)  2 0/30 (0.00%)  0 0/1 (0.00%)  0
Ecchymosis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  2 0/30 (0.00%)  0 0/1 (0.00%)  0
Erythema  1  2/22 (9.09%)  2 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  2 0/30 (0.00%)  0 0/1 (0.00%)  0
Petechiae  1  2/22 (9.09%)  2 2/21 (9.52%)  2 2/19 (10.53%)  2 0/28 (0.00%)  0 0/15 (0.00%)  0 2/30 (6.67%)  2 0/1 (0.00%)  0
Pruritus  1  3/22 (13.64%)  3 5/21 (23.81%)  5 1/19 (5.26%)  1 3/28 (10.71%)  5 2/15 (13.33%)  5 3/30 (10.00%)  3 0/1 (0.00%)  0
Rash  1  4/22 (18.18%)  4 1/21 (4.76%)  1 2/19 (10.53%)  3 4/28 (14.29%)  5 2/15 (13.33%)  2 5/30 (16.67%)  5 0/1 (0.00%)  0
Red man syndrome  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 1/28 (3.57%)  1 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Dermatitis diaper  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Surgical and medical procedures               
Central venous catheter removal  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Central venous catheterisation  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Vascular disorders               
Flushing  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Hypertension  1  4/22 (18.18%)  5 1/21 (4.76%)  1 1/19 (5.26%)  1 3/28 (10.71%)  3 2/15 (13.33%)  3 2/30 (6.67%)  2 0/1 (0.00%)  0
Hypotension  1  1/22 (4.55%)  1 3/21 (14.29%)  3 0/19 (0.00%)  0 3/28 (10.71%)  3 2/15 (13.33%)  2 2/30 (6.67%)  2 0/1 (0.00%)  0
Venoocclusive disease  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/19 (0.00%)  0 0/28 (0.00%)  0 1/15 (6.67%)  1 0/30 (0.00%)  0 0/1 (0.00%)  0
Pallor  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/19 (5.26%)  1 0/28 (0.00%)  0 0/15 (0.00%)  0 0/30 (0.00%)  0 0/1 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.0
Only 1 participant was enrolled in the POS 12 TID 3 months to <2 years group, limiting conclusions that may be drawn for pharmacokinetics or safety.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator 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 study. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation with regard to proprietary information, accuracy, fair balance, and compliance.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01716234     History of Changes
Other Study ID Numbers: P03579
2007-004645-15 ( EudraCT Number )
MK-5592-032 ( Other Identifier: Merck )
First Submitted: October 25, 2012
First Posted: October 29, 2012
Results First Submitted: March 15, 2016
Results First Posted: April 15, 2016
Last Update Posted: August 27, 2018