Maribavir for Treatment of Resistant or Refractory CMV Infections in Transplant Recipients
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
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
- 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).
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
Inclusion Criteria
-
Be ≥12 years of age.
-
Weigh ≥ 40 kg.
-
Be a recipient of stem cell or solid organ transplantation.
-
Have documented CMV infection in blood or plasma, with a screening value of ≥1,000 DNA copies/mL.
-
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.
-
If female, be either postmenopausal, surgically sterile, or have a negative pregnancy test prior to randomization.
-
Be able to swallow tablets.
-
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).
-
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
-
Be receiving any other anti-CMV agent(s).
-
Have a current CMV infection that is considered resistant or refractory due to inadequate adherence to prior oral anti-CMV treatment.
-
Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the time of enrollment.
-
Have severe hepatic impairment.
-
Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
-
Have expected survival less than 6 weeks.
-
Be pregnant or breastfeeding.
-
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.- 1263-202
- SHP620-202
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
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%
|
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%
|
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%
|
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
|
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
|
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)
|
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)
|
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)
|
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)
|
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
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 |
ClinicalTransparency@shire.com |
- 1263-202
- SHP620-202