Maribavir for Treatment of Resistant or Refractory CMV Infections in Transplant Recipients

Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT01611974
Collaborator
(none)
120
32
3
28.6
3.8
0.1

Study Details

Study Description

Brief Summary

This study will assess safety, antiviral activity, and pharmacokinetics of different doses of maribavir administered orally for up to 24 weeks for treatment of CMV infections that are resistant or refractory to treatment with ganciclovir/valganciclovir or foscarnet in recipients of stem cell or solid organ transplants.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized Study to Assess the Safety and Anti-cytomegalovirus (CMV) Activity of Different Doses of Maribavir for Treatment of CMV Infections That Are Resistant or Refractory to Treatment With Ganciclovir/Valganciclovir or Foscarnet in Transplant Recipients
Actual Study Start Date :
Jul 17, 2012
Actual Primary Completion Date :
Dec 5, 2014
Actual Study Completion Date :
Dec 5, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Maribavir 400 mg twice daily

Drug: Maribavir
Tablet for oral administration

Experimental: Maribavir 800 mg twice daily

Drug: Maribavir
Tablet for oral administration

Experimental: Maribavir 1200 mg twice daily

Drug: Maribavir
Tablet for oral administration

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Confirmed Undetectable Plasma Cytomegalovirus (CMV) Within 6 Weeks [6 weeks]

    Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. This method was linear over 200-100,000 viral copies/mL with a lower limit of quantification (LLOQ) of 200 copies/mL. Results below LLOQ were considered undetectable. Confirmed undetectable plasma CMV DNA within 6 weeks was defined as 2 consecutive post-baseline, on-treatment undetectable results separated by >/= 5 days (assessed by the central laboratory). Samples were collected on Days 1 and 8, weekly during Weeks 2-6, and once in Weeks 8, 10, 12, 16, 20, 24 (treatment) and Weeks 1, 4, 8, 12 (follow-up). Permissible assessment windows were: Days 8-15 +/- 1 day; Weeks 3-4 +/- 2 days; Weeks 5-6 +/- 3 days; Weeks 8-12 +/- 4 days; Weeks 16-24 +/- 7 days (treatment) and Weeks 1-4 +/- 2 days; Weeks 8-12 +/- 4 days (follow-up).

  2. Number of Participants With a Treatment Emergent Adverse Event (TEAE). [25 weeks]

    Treatment-emergent adverse events are those events that occurred on or after study drug administration through 7 days after the last dose of study drug, or are events that occurred prior to study drug administration and recurred with increased severity after taking study drug through 7 days after the last dose of study drug.

Secondary Outcome Measures

  1. Number of Participants With CMV Recurrence [36 weeks]

    Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. CMV recurrence was defined as achievement of undetectable plasma CMV DNA at any time after Day 1 in at least 2 consecutive samples separated by at least 5 days, followed by detectable plasma CMV DNA in at least 2 consecutive samples separated by at least 5 days (assessed by the central laboratory). For the analyses of CMV recurrence, the first of 2 consecutive confirmed undetectable plasma CMV DNA results had to be on-treatment. CMV DNA PCR values of ≥200 copies/mL were considered detectable. Participants assessed for recurrence (n= 29, 27, 30) are the subset of the ITT-S who had at least 2 consecutive undetectable plasma CMV DNA results separated by at least 5 days, including early withdrawn qualified subjects.

  2. Time to First Confirmed Undetectable Plasma CMV DNA Within 6 Weeks and at Any Time During The Study [6 weeks after start of treatment, within 36 weeks of start of treatment]

    Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. The time to event was defined as the time from first dose of study drug to first undetectable plasma CMV DNA within 6 weeks and at any time during the study, defined as the date of the first of at least 2 consecutive post-baseline, on-treatment undetectable results (<200 copies/mL) separated by at least 5 days; as assessed by the central laboratory. The median values are Kaplan-Meier estimates.

  3. Time to CMV Recurrence [36 weeks]

    Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. The time to event was defined as the time of the first of at least 2 consecutive samples, separated by at least 5 days, with detectable plasma CMV DNA after achievement of undetectable plasma CMV DNA in at least 2 consecutive samples, separated by at least 5 days, at any time after Day 1; as assessed by the central laboratory. Participants assessed for recurrence (n= 29, 27, 30) are the subset of the ITT-S who had at least 2 consecutive undetectable plasma CMV DNA results separated by at least 5 days, including early withdrawn qualified subjects. The median values are Kaplan-Meier estimates.

  4. Maximum Concentration (Cmax) of Maribavir [pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit]

    For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.

  5. Time to Maximum Concentration (Tmax) of Maribavir [pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit]

    For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.

  6. Time of Last Non-Zero Concentration (Tlast) of Maribavir [pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit]

    For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.

  7. Area Under The Plasma Concentration Versus Time Curve From The Time of Dosing to The Last Measurable Concentration (AUClast) of Maribavir [pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit]

    For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.

  8. Half-Life (T½) of Maribavir [pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit]

    For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria

  1. Be ≥12 years of age.

  2. Weigh ≥ 40 kg.

  3. Be a recipient of stem cell or solid organ transplantation.

  4. Have documented CMV infection in blood or plasma, with a screening value of ≥1,000 DNA copies/mL.

  5. Have a current CMV infection that is resistant (known CMV genetic mutations) or refractory (clinical failure to respond) to treatment with ganciclovir/valganciclovir and/or foscarnet.

  6. If female, be either postmenopausal, surgically sterile, or have a negative pregnancy test prior to randomization.

  7. Be able to swallow tablets.

  8. If adult, provide written informed consent. If child (age <18 years), have a parent/legal guardian who is willing and able to provide written informed consent (with assent from the child when appropriate).

  9. Be assessed by the investigator to determine whether prophylaxis for non-CMV herpesvirus infections (e.g., herpes simplex virus [HSV type 1 and type 2] and varicella zoster virus [VZV]) is appropriate according to institutional guidelines or standard practices, keeping in mind that maribavir is not active in vitro against these viruses.

Exclusion Criteria

  1. Be receiving any other anti-CMV agent(s).

  2. Have a current CMV infection that is considered resistant or refractory due to inadequate adherence to prior oral anti-CMV treatment.

  3. Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the time of enrollment.

  4. Have severe hepatic impairment.

  5. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.

  6. Have expected survival less than 6 weeks.

  7. Be pregnant or breastfeeding.

  8. Other clinically significant medical or surgical condition.

Contacts and Locations

Locations

Site City State Country Postal Code
1 UCLA Medical Center Los Angeles California United States 90095
2 Stanford University Medical Center Stanford California United States 94305
3 University of Colorado Denver Colorado United States 80045
4 Yale University New Haven Connecticut United States 06520
5 University of Florida Gainesville Florida United States 32610
6 Tampa General Hospital Tampa Florida United States 33614
7 Emory University Atlanta Georgia United States 30322
8 Northwestern University Medical Center Chicago Illinois United States 60611
9 University of Chicago Chicago Illinois United States 60637
10 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
11 Johns Hopkins Hospital Baltimore Maryland United States 21205
12 Brigham and Women's Hospital Boston Massachusetts United States 02115
13 University of Massachusetts Worcester Massachusetts United States 01655
14 University of Michigan Ann Arbor Michigan United States 48109
15 Henry Ford Health Care System Detroit Michigan United States 48202
16 University of Minnesota Medical Center Minneapolis Minnesota United States 55454
17 University of Nebraska Omaha Nebraska United States 68198
18 Columbia University New York New York United States 10032
19 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
20 Duke University Medical Center Durham North Carolina United States 30322
21 Wake Forest Medical Center Winston-Salem North Carolina United States 27157
22 Cleveland Clinic Foundation Cleveland Ohio United States 44195
23 Nationwide Children's Hospital Columbus Ohio United States 43205
24 University of Pennsylvania Philadelphia Pennsylvania United States 19104
25 Albert Einstein Medical Center Philadelphia Pennsylvania United States 19141
26 University of Pittsburg Pittsburgh Pennsylvania United States 15213
27 Medical University of South Carolina Charleston South Carolina United States 29425
28 Vanderbilt Medical Center Nashville Tennessee United States 37212
29 Methodist Healthcare System San Antonio Texas United States 78229
30 University of Utah Salt Lake City Utah United States 84132
31 University of Washington Seattle Washington United States 98109
32 Fred Hutchinson Cancer Research Center Seattle Washington United States 98195

Sponsors and Collaborators

  • Shire

Investigators

  • Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Shire
ClinicalTrials.gov Identifier:
NCT01611974
Other Study ID Numbers:
  • 1263-202
  • SHP620-202
First Posted:
Jun 5, 2012
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Shire
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Period Title: Overall Study
STARTED 40 40 40
COMPLETED 25 25 24
NOT COMPLETED 15 15 16

Baseline Characteristics

Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily Total
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Total of all reporting groups
Overall Participants 40 40 40 120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
52.1
(14.25)
55.4
(14.13)
50.0
(12.96)
52.5
(13.86)
Age, Customized (Count of Participants)
18 to 44 years
11
27.5%
10
25%
14
35%
35
29.2%
45 to 64 years
22
55%
18
45%
20
50%
60
50%
65 to 75 years
7
17.5%
12
30%
6
15%
25
20.8%
Sex: Female, Male (Count of Participants)
Female
19
47.5%
16
40%
16
40%
51
42.5%
Male
21
52.5%
24
60%
24
60%
69
57.5%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Confirmed Undetectable Plasma Cytomegalovirus (CMV) Within 6 Weeks
Description Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. This method was linear over 200-100,000 viral copies/mL with a lower limit of quantification (LLOQ) of 200 copies/mL. Results below LLOQ were considered undetectable. Confirmed undetectable plasma CMV DNA within 6 weeks was defined as 2 consecutive post-baseline, on-treatment undetectable results separated by >/= 5 days (assessed by the central laboratory). Samples were collected on Days 1 and 8, weekly during Weeks 2-6, and once in Weeks 8, 10, 12, 16, 20, 24 (treatment) and Weeks 1, 4, 8, 12 (follow-up). Permissible assessment windows were: Days 8-15 +/- 1 day; Weeks 3-4 +/- 2 days; Weeks 5-6 +/- 3 days; Weeks 8-12 +/- 4 days; Weeks 16-24 +/- 7 days (treatment) and Weeks 1-4 +/- 2 days; Weeks 8-12 +/- 4 days (follow-up).
Time Frame 6 weeks

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat Safety population, defined as all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 40 40 38
Number [participants]
28
70%
25
62.5%
27
67.5%
2. Primary Outcome
Title Number of Participants With a Treatment Emergent Adverse Event (TEAE).
Description Treatment-emergent adverse events are those events that occurred on or after study drug administration through 7 days after the last dose of study drug, or are events that occurred prior to study drug administration and recurred with increased severity after taking study drug through 7 days after the last dose of study drug.
Time Frame 25 weeks

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat Safety population, defined as all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 40 40 40
Any TEAE
40
100%
40
100%
40
100%
Serious TEAE
28
70%
27
67.5%
26
65%
3. Secondary Outcome
Title Number of Participants With CMV Recurrence
Description Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. CMV recurrence was defined as achievement of undetectable plasma CMV DNA at any time after Day 1 in at least 2 consecutive samples separated by at least 5 days, followed by detectable plasma CMV DNA in at least 2 consecutive samples separated by at least 5 days (assessed by the central laboratory). For the analyses of CMV recurrence, the first of 2 consecutive confirmed undetectable plasma CMV DNA results had to be on-treatment. CMV DNA PCR values of ≥200 copies/mL were considered detectable. Participants assessed for recurrence (n= 29, 27, 30) are the subset of the ITT-S who had at least 2 consecutive undetectable plasma CMV DNA results separated by at least 5 days, including early withdrawn qualified subjects.
Time Frame 36 weeks

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat Safety population, defined as all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 40 40 40
Number [participants]
7
17.5%
11
27.5%
12
30%
4. Secondary Outcome
Title Time to First Confirmed Undetectable Plasma CMV DNA Within 6 Weeks and at Any Time During The Study
Description Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. The time to event was defined as the time from first dose of study drug to first undetectable plasma CMV DNA within 6 weeks and at any time during the study, defined as the date of the first of at least 2 consecutive post-baseline, on-treatment undetectable results (<200 copies/mL) separated by at least 5 days; as assessed by the central laboratory. The median values are Kaplan-Meier estimates.
Time Frame 6 weeks after start of treatment, within 36 weeks of start of treatment

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat Safety population, defined as all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 40 40 40
Within 6 weeks, n = 40, 40, 38
24.0
28.0
22.0
Anytime during the study, n = 40, 40, 40
24.0
28.0
22.0
5. Secondary Outcome
Title Time to CMV Recurrence
Description Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. The time to event was defined as the time of the first of at least 2 consecutive samples, separated by at least 5 days, with detectable plasma CMV DNA after achievement of undetectable plasma CMV DNA in at least 2 consecutive samples, separated by at least 5 days, at any time after Day 1; as assessed by the central laboratory. Participants assessed for recurrence (n= 29, 27, 30) are the subset of the ITT-S who had at least 2 consecutive undetectable plasma CMV DNA results separated by at least 5 days, including early withdrawn qualified subjects. The median values are Kaplan-Meier estimates.
Time Frame 36 weeks

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat Safety population, defined as all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 40 40 40
Median (95% Confidence Interval) [days]
NA
118.0
161.0
6. Secondary Outcome
Title Maximum Concentration (Cmax) of Maribavir
Description For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Time Frame pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic Profile Population, defined as all participants in the ITT-S Population who had plasma samples drawn and tested for maribavir concentrations
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 12 13 8
Visit 3, n = 12, 10, 8
18.5
(7.39)
35.1
(12.0)
45.1
(21.2)
Visit 6, n = 8, 10, 6
17.8
(8.36)
25.0
(9.69)
35.6
(25.8)
7. Secondary Outcome
Title Time to Maximum Concentration (Tmax) of Maribavir
Description For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Time Frame pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic Profile Population, defined as all participants in the ITT-S Population who had plasma samples drawn and tested for maribavir concentrations.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 12 13 8
Visit 3, n = 12, 10, 8
3.56
(2.99)
2.70
(2.89)
2.81
(2.02)
Visit 6, n = 8, 10, 6
1.66
(0.765)
3.23
(2.28)
3.12
(1.05)
8. Secondary Outcome
Title Time of Last Non-Zero Concentration (Tlast) of Maribavir
Description For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Time Frame pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic Profile Population, defined as all participants in the ITT-S Population who had plasma samples drawn and tested for maribavir concentrations.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 12 13 8
Visit 3, n = 12, 10, 8
9.03
(2.55)
8.26
(2.48)
8.71
(1.45)
Visit 6, n = 8, 10, 6
7.37
(3.70)
7.99
(1.65)
8.61
(1.64)
9. Secondary Outcome
Title Area Under The Plasma Concentration Versus Time Curve From The Time of Dosing to The Last Measurable Concentration (AUClast) of Maribavir
Description For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Time Frame pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic Profile Population, defined as all participants in the ITT-S Population who had plasma samples drawn and tested for maribavir concentrations.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 12 13 8
Visit 3, n = 12, 10, 8
100
(50.4)
179
(69.6)
264
(147)
Visit 6, n = 8, 10, 6
90.9
(64.3)
139
(61.3)
207
(161)
10. Secondary Outcome
Title Half-Life (T½) of Maribavir
Description For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Time Frame pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic Profile Population, defined as all participants in the ITT-S Population who had plasma samples drawn and tested for maribavir concentrations.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
Measure Participants 12 13 8
Visit 3, n = 6, 7, 3
5.56
(3.85)
6.08
(3.51)
7.77
(3.59)
Visit 6, n = 5, 5, 3
4.32
(1.25)
6.34
(1.41)
5.33
(2.55)

Adverse Events

Time Frame
Adverse Event Reporting Description Treatment emergent AEs are reported for the Intent-to-Treat Safety Population, defined as all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Arm/Group Description Participants received oral maribavir at 400 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 800 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks. Participants received oral maribavir at 1200 mg twice daily for a maximum duration of 24 weeks. Participants were then followed for 12 weeks.
All Cause Mortality
Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 28/40 (70%) 27/40 (67.5%) 26/40 (65%)
Blood and lymphatic system disorders
Anaemia 4/40 (10%) 0/40 (0%) 0/40 (0%)
Haemolysis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Pancytopenia 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Cardiac disorders
Cardiac tamponade 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Pericardial effusion 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Cardiac failure congestive 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Eye disorders
Vision blurred 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Gastrointestinal disorders
Abdominal pain 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Ascites 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Haematemesis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Small intestinal obstruction 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Diarrhoea 0/40 (0%) 2/40 (5%) 1/40 (2.5%)
Gastrointestinal haemorrhage 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Ileus 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Nausea 1/40 (2.5%) 3/40 (7.5%) 3/40 (7.5%)
Pancreatitis 0/40 (0%) 1/40 (2.5%) 1/40 (2.5%)
Vomiting 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Jejunal ulcer 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
General disorders
Fatigue 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Multi-organ failure 1/40 (2.5%) 1/40 (2.5%) 2/40 (5%)
Pyrexia 2/40 (5%) 1/40 (2.5%) 0/40 (0%)
Asthenia 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Generalised oedema 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Oedema peripheral 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Hepatobiliary disorders
Bile duct stenosis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Cholecystitis 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Immune system disorders
Acute graft versus host disease 1/40 (2.5%) 0/40 (0%) 1/40 (2.5%)
Lung transplant rejection 2/40 (5%) 1/40 (2.5%) 1/40 (2.5%)
Infections and infestations
Adenovirus infection 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Appendicitis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Bacteraemia 1/40 (2.5%) 2/40 (5%) 0/40 (0%)
Bacterial sepsis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Bronchiolitis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Clostridium difficile infection 2/40 (5%) 0/40 (0%) 1/40 (2.5%)
Cytomegalovirus gastroenteritis 2/40 (5%) 0/40 (0%) 0/40 (0%)
Cytomegalovirus infection 3/40 (7.5%) 5/40 (12.5%) 6/40 (15%)
Encephalitis viral 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Escherichia bacteraemia 1/40 (2.5%) 0/40 (0%) 1/40 (2.5%)
Pneumonia 1/40 (2.5%) 2/40 (5%) 1/40 (2.5%)
Sepsis 2/40 (5%) 3/40 (7.5%) 1/40 (2.5%)
Cytomegalovirus chorioretinitis 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Encephalitis cytomegalovirus 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Herpes simplex meningoencephalitis 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Klebsiella bacteraemia 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Parvovirus infection 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Urinary tract infection 0/40 (0%) 1/40 (2.5%) 1/40 (2.5%)
Arteriovenous fistula site infection 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Catheter site infection 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Cellulitis 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Nocardiosis 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Pneumocystis jirovecii pneumonia 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Pneumonia cytomegaloviral 1/40 (2.5%) 0/40 (0%) 2/40 (5%)
Respiratory syncytial virus infection 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Rhinovirus infection 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Injury, poisoning and procedural complications
Blood stem cell transplant failure 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Fall 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Investigations
Oxygen saturation decreased 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Immunosuppresant drug level increased 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Metabolism and nutrition disorders
Dehydration 1/40 (2.5%) 1/40 (2.5%) 2/40 (5%)
Failure to thrive 1/40 (2.5%) 1/40 (2.5%) 1/40 (2.5%)
Gout 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Hyponatraemia 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Fluid overload 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Hyperglycaemia 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Hypokalaemia 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Hyperkalaemia 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia recurrent 2/40 (5%) 0/40 (0%) 1/40 (2.5%)
Oesophageal carcinoma 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Post transplant lymphoproliferative disorder 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Nervous system disorders
Central nervous system haemorrhage 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Encephalopathy 1/40 (2.5%) 1/40 (2.5%) 0/40 (0%)
Spondylitic myelopathy 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Convulsion 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Psychiatric disorders
Mental status changes 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Renal and urinary disorders
Acute prerenal failure 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Focal segmental glomerulosclerosis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Renal impairment 2/40 (5%) 3/40 (7.5%) 2/40 (5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Dyspnoea exertional 0/40 (0%) 1/40 (2.5%) 0/40 (0%)
Acute respiratory distress syndrome 0/40 (0%) 0/40 (0%) 2/40 (5%)
Diffuse alveolar damage 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Respiratory failure 0/40 (0%) 0/40 (0%) 3/40 (7.5%)
Vascular disorders
Hypotension 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Jugular vein thrombosis 1/40 (2.5%) 0/40 (0%) 0/40 (0%)
Orthostatic hypotension 0/40 (0%) 0/40 (0%) 1/40 (2.5%)
Other (Not Including Serious) Adverse Events
Maribavir 400 mg Twice Daily Maribavir 800 mg Twice Daily Maribavir 1200 mg Twice Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 40/40 (100%) 40/40 (100%) 40/40 (100%)
Blood and lymphatic system disorders
Anaemia 3/40 (7.5%) 7/40 (17.5%) 10/40 (25%)
Leukopenia 1/40 (2.5%) 3/40 (7.5%) 4/40 (10%)
Thrombocytopenia 3/40 (7.5%) 3/40 (7.5%) 2/40 (5%)
Leukocytosis 3/40 (7.5%) 1/40 (2.5%) 3/40 (7.5%)
Haemolytic anaemia 1/40 (2.5%) 1/40 (2.5%) 3/40 (7.5%)
Neutropenia 2/40 (5%) 1/40 (2.5%) 2/40 (5%)
Coagulopathy 0/40 (0%) 2/40 (5%) 2/40 (5%)
Cardiac disorders
Sinus tachycardia 2/40 (5%) 2/40 (5%) 1/40 (2.5%)
Angina pectoris 0/40 (0%) 3/40 (7.5%) 1/40 (2.5%)
Tachycardia 2/40 (5%) 1/40 (2.5%) 1/40 (2.5%)
Pericardial effusion 2/40 (5%) 0/40 (0%) 1/40 (2.5%)
Atrial fibrillation 0/40 (0%) 0/40 (0%) 2/40 (5%)
Left ventricular hypertrophy 0/40 (0%) 0/40 (0%) 2/40 (5%)
Endocrine disorders
Hypothyroidism 0/40 (0%) 3/40 (7.5%) 1/40 (2.5%)
Eye disorders
Visual impairment 0/40 (0%) 0/40 (0%) 3/40 (7.5%)
Gastrointestinal disorders
Nausea 14/40 (35%) 9/40 (22.5%) 12/40 (30%)
Vomiting 11/40 (27.5%) 12/40 (30%) 11/40 (27.5%)
Diarrhoea 5/40 (12.5%) 11/40 (27.5%) 10/40 (25%)
Constipation 5/40 (12.5%) 5/40 (12.5%) 5/40 (12.5%)
Abdominal pain 2/40 (5%) 4/40 (10%) 3/40 (7.5%)
Ascites 3/40 (7.5%) 1/40 (2.5%) 3/40 (7.5%)
Dyspepsia 2/40 (5%) 2/40 (5%) 1/40 (2.5%)
Abdominal distension 1/40 (2.5%) 1/40 (2.5%) 2/40 (5%)
Dysphagia 2/40 (5%) 1/40 (2.5%) 0/40 (0%)
Proctalgia 2/40 (5%) 0/40 (0%) 0/40 (0%)
General disorders
Fatigue 7/40 (17.5%) 10/40 (25%) 7/40 (17.5%)
Oedema peripheral 11/40 (27.5%) 5/40 (12.5%) 6/40 (15%)
Pyrexia 4/40 (10%) 5/40 (12.5%) 3/40 (7.5%)
Chills 2/40 (5%) 2/40 (5%) 4/40 (10%)
Local swelling 2/40 (5%) 1/40 (2.5%) 2/40 (5%)
Pain 2/40 (5%) 2/40 (5%) 1/40 (2.5%)
Asthenia 1/40 (2.5%) 1/40 (2.5%) 2/40 (5%)
Generalised oedema 0/40 (0%) 1/40 (2.5%) 2/40 (5%)
Malaise 2/40 (5%) 0/40 (0%) 2/40 (5%)
Gait disturbance 1/40 (2.5%) 2/40 (5%) 0/40 (0%)
Swelling 2/40 (5%) 0/40 (0%) 0/40 (0%)
Immune system disorders
Acute graft versus host disease 1/40 (2.5%) 4/40 (10%) 2/40 (5%)
Lung transplant rejection 2/40 (5%) 0/40 (0%) 0/40 (0%)
Hypogammaglobulinaemia 2/40 (5%) 1/40 (2.5%) 1/40 (2.5%)
Infections and infestations
Cytomegalovirus infection 3/40 (7.5%) 8/40 (20%) 4/40 (10%)
Pneumonia 5/40 (12.5%) 3/40 (7.5%) 4/40 (10%)
Urinary tract infection 6/40 (15%) 2/40 (5%) 2/40 (5%)
Clostridium difficile infection 2/40 (5%) 2/40 (5%) 4/40 (10%)
Oral candidiasis 1/40 (2.5%) 1/40 (2.5%) 4/40 (10%)
Upper respiratory tract infection 2/40 (5%) 3/40 (7.5%) 1/40 (2.5%)
BK virus infection 3/40 (7.5%) 1/40 (2.5%) 1/40 (2.5%)
Genital herpes 0/40 (0%) 2/40 (5%) 1/40 (2.5%)
Klebsiella bacteraemia 0/40 (0%) 0/40 (0%) 2/40 (5%)
Nasopharyngitis 1/40 (2.5%) 2/40 (5%) 0/40 (0%)
Injury, poisoning and procedural complications
Procedural complication 0/40 (0%) 2/40 (5%) 1/40 (2.5%)
Fall 0/40 (0%) 2/40 (5%) 0/40 (0%)
Investigations
Immunosuppressant drug level increased 4/40 (10%) 2/40 (5%) 5/40 (12.5%)
Weight decreased 2/40 (5%) 3/40 (7.5%) 4/40 (10%)
Bacterial test positive 2/40 (5%) 3/40 (7.5%) 1/40 (2.5%)
Blood creatinine increased 1/40 (2.5%) 3/40 (7.5%) 2/40 (5%)
Hepatic enzyme increased 3/40 (7.5%) 3/40 (7.5%) 0/40 (0%)
Blood alkaline phosphatase increased 1/40 (2.5%) 2/40 (5%) 0/40 (0%)
Weight increased 2/40 (5%) 1/40 (2.5%) 0/40 (0%)
Blood urea increased 0/40 (0%) 2/40 (5%) 0/40 (0%)
Neutrophil count increased 0/40 (0%) 0/40 (0%) 2/40 (5%)
Metabolism and nutrition disorders
Decreased appetite 3/40 (7.5%) 5/40 (12.5%) 4/40 (10%)
Dehydration 4/40 (10%) 3/40 (7.5%) 1/40 (2.5%)
Hypokalaemia 2/40 (5%) 4/40 (10%) 5/40 (12.5%)
Hyperkalaemia 2/40 (5%) 3/40 (7.5%) 4/40 (10%)
Hyperglycaemia 2/40 (5%) 2/40 (5%) 2/40 (5%)
Fluid overload 4/40 (10%) 1/40 (2.5%) 0/40 (0%)
Hypocalcaemia 3/40 (7.5%) 1/40 (2.5%) 0/40 (0%)
Hyponatraemia 0/40 (0%) 1/40 (2.5%) 2/40 (5%)
Hypophosphataemia 2/40 (5%) 2/40 (5%) 0/40 (0%)
Hypernatraemia 0/40 (0%) 2/40 (5%) 1/40 (2.5%)
Hypervolaemia 0/40 (0%) 0/40 (0%) 2/40 (5%)
Hypomagnesaemia 0/40 (0%) 0/40 (0%) 2/40 (5%)
Musculoskeletal and connective tissue disorders
Back pain 4/40 (10%) 1/40 (2.5%) 4/40 (10%)
Arthralgia 3/40 (7.5%) 3/40 (7.5%) 2/40 (5%)
Pain in extremity 1/40 (2.5%) 4/40 (10%) 0/40 (0%)
Musculoskeletal pain 3/40 (7.5%) 0/40 (0%) 1/40 (2.5%)
Myalgia 2/40 (5%) 1/40 (2.5%) 1/40 (2.5%)
Neck pain 0/40 (0%) 3/40 (7.5%) 1/40 (2.5%)
Nervous system disorders
Dysgeusia 24/40 (60%) 25/40 (62.5%) 29/40 (72.5%)
Headache 9/40 (22.5%) 4/40 (10%) 6/40 (15%)
Dizziness 1/40 (2.5%) 5/40 (12.5%) 3/40 (7.5%)
Neuropathy peripheral 1/40 (2.5%) 2/40 (5%) 2/40 (5%)
Dysaesthesia 0/40 (0%) 1/40 (2.5%) 2/40 (5%)
Somnolence 0/40 (0%) 1/40 (2.5%) 2/40 (5%)
Psychiatric disorders
Depression 2/40 (5%) 8/40 (20%) 1/40 (2.5%)
Insomnia 2/40 (5%) 3/40 (7.5%) 1/40 (2.5%)
Anxiety 0/40 (0%) 4/40 (10%) 1/40 (2.5%)
Libido decreased 0/40 (0%) 0/40 (0%) 2/40 (5%)
Renal and urinary disorders
Renal impairment 1/40 (2.5%) 4/40 (10%) 7/40 (17.5%)
Urinary incontinence 1/40 (2.5%) 3/40 (7.5%) 1/40 (2.5%)
Proteinuria 0/40 (0%) 1/40 (2.5%) 2/40 (5%)
Urinary retention 0/40 (0%) 0/40 (0%) 3/40 (7.5%)
Respiratory, thoracic and mediastinal disorders
Cough 5/40 (12.5%) 6/40 (15%) 2/40 (5%)
Dyspnoea 4/40 (10%) 2/40 (5%) 5/40 (12.5%)
Hypoxia 4/40 (10%) 2/40 (5%) 2/40 (5%)
Oropharyngeal pain 2/40 (5%) 2/40 (5%) 0/40 (0%)
Dyspnoea exertional 0/40 (0%) 0/40 (0%) 2/40 (5%)
Haemoptysis 0/40 (0%) 1/40 (2.5%) 2/40 (5%)
Nasal congestion 2/40 (5%) 0/40 (0%) 1/40 (2.5%)
Pleural effusion 2/40 (5%) 0/40 (0%) 1/40 (2.5%)
Rhinorrhoea 0/40 (0%) 3/40 (7.5%) 0/40 (0%)
Skin and subcutaneous tissue disorders
Rash 7/40 (17.5%) 6/40 (15%) 3/40 (7.5%)
Pruritus 5/40 (12.5%) 1/40 (2.5%) 5/40 (12.5%)
Ecchymosis 1/40 (2.5%) 2/40 (5%) 1/40 (2.5%)
Alopecia 2/40 (5%) 1/40 (2.5%) 0/40 (0%)
Blood blister 2/40 (5%) 0/40 (0%) 1/40 (2.5%)
Decubitus ulcer 0/40 (0%) 2/40 (5%) 1/40 (2.5%)
Erythema 2/40 (5%) 1/40 (2.5%) 0/40 (0%)
Night sweats 0/40 (0%) 2/40 (5%) 1/40 (2.5%)
Skin lesion 0/40 (0%) 2/40 (5%) 0/40 (0%)
Vascular disorders
Hypotension 4/40 (10%) 5/40 (12.5%) 1/40 (2.5%)
Hypertension 3/40 (7.5%) 3/40 (7.5%) 0/40 (0%)
Flushing 1/40 (2.5%) 0/40 (0%) 2/40 (5%)
Hot flush 0/40 (0%) 0/40 (0%) 2/40 (5%)
Thrombophlebitis 0/40 (0%) 2/40 (5%) 0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.

Results Point of Contact

Name/Title Study Director
Organization Shire
Phone +1 866 842 5335
Email ClinicalTransparency@shire.com
Responsible Party:
Shire
ClinicalTrials.gov Identifier:
NCT01611974
Other Study ID Numbers:
  • 1263-202
  • SHP620-202
First Posted:
Jun 5, 2012
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021