ClinicalTrials.gov
ClinicalTrials.gov Menu

Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00497796
Recruitment Status : Completed
First Posted : July 9, 2007
Results First Posted : June 4, 2015
Last Update Posted : June 4, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Condition Cytomegalovirus Infections
Interventions Drug: maribavir
Drug: ganciclovir
Enrollment 307
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description Maribavir: 100mg twice a day (BID) for 14 weeks. Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Period Title: Overall Study
Started 147 160
Completed 62 101
Not Completed 85 59
Reason Not Completed
Adverse event (not related)             9             9
Adverse event (related)             5             4
CMV infection or disease treatment             30             4
Consent withdrawn             10             3
Investigator/sponsor discretion             31             34
Lost to Follow-up             0             1
Not applicable (randomized not treated)             0             4
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID Total
Hide Arm/Group Description Maribavir: 100mg twice a day (BID) for 14 weeks. Ganciclovir: 1000mg three times per (TID) day for 14 weeks. Total of all reporting groups
Overall Number of Baseline Participants 147 156 303
Hide Baseline Analysis Population Description
The Intent-to-Treat Safety (ITT-S) population, defined as all randomized subjects who received at least one dose of study drug, regardless of whether they had any post-baseline evaluations.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 147 participants 156 participants 303 participants
55  (9.0) 53  (8.9) 54  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 147 participants 156 participants 303 participants
Female
27
  18.4%
37
  23.7%
64
  21.1%
Male
120
  81.6%
119
  76.3%
239
  78.9%
Distribution of age  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 147 participants 156 participants 303 participants
18 to 44 years 19 22 41
45 to 64 years 109 123 232
65 to 75 years 19 11 30
1.Primary Outcome
Title Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation
Hide Description All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction [PCR] assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame 6 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The modified Intent-to-Treat (ITT-M) population, defined as all randomized subjects who received at least one dose of study drug and had participated in the study for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 113 120
Measure Type: Number
Unit of Measure: number of participants with event
14 10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Based on the ICH guidance, the hypothesis of non-inferiority can be tested using a one-sided 97.5% confidence interval’s (CI) upper bound comparing with the non-inferiority margin of 5% (0.05).
Method of Estimation Estimation Parameter Rate difference
Estimated Value 0.041
Confidence Interval (2-Sided) 95%
-0.038 to 0.119
Estimation Comments Rate difference is the rate of maribavir minus the rate of ganciclovir
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2754
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.586
Confidence Interval (2-Sided) 95%
0.682 to 3.690
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
Hide Description Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy.
Time Frame 6 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-M population, defined as all randomized subjects who received at least one dose of study drug and had participated in the study for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 113 120
Measure Type: Number
Unit of Measure: participants
pp65 antigenemia assay 63 49
CMV DNA PCR assay 72 52
pp65 antigenemia or CMV DNA PCR assay 81 64
Initiation of anti-CMV therapy 46 39
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of the pp65 antigenemia assay
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0283
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.793
Confidence Interval (2-Sided) 95%
1.065 to 3.020
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of CMV DNA PCR assay
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.284
Confidence Interval (2-Sided) 95%
1.338 to 3.900
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of pp65 antigenemia or CMV DNA PCR assay
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0053
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.177
Confidence Interval (2-Sided) 95%
1.259 to 3.767
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of initiation of anti-CMV therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2339
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.388
Confidence Interval (2-Sided) 95%
0.811 to 2.377
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
3.Secondary Outcome
Title Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
Hide Description All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by pp65 Antigenemia or CMV DNA PCR from a central or local lab. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame 6 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-M population, defined as all randomized subjects who received at least one dose of study drug and had participated in the study for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 113 120
Median (Inter-Quartile Range)
Unit of Measure: days
45
(41 to 68)
127
(125 to 161)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of time to onset
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
1.62 to 3.14
Estimation Comments Maribavir versus ganciclovir; Cox’s proportional hazards regression model: time = receipt of induction ALA and geographic region (US or Europe) + treatment.
4.Secondary Outcome
Title Number of Participants With Investigator-determined CMV Disease
Hide Description Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction [PCR] assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame Through 6 months post-transplant (Day 1 to 100 days and 6 months post-transplant)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-M population, defined as all randomized subjects who received at least one dose of study drug and had participated in the study for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 113 120
Measure Type: Number
Unit of Measure: participants
100 days post-transplant 17 3
6 months post-transplant 22 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of 100 days post-transplant
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of 6 months post-transplant
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3742
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation
Hide Description All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction [PCR] assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame 100 days post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-M population, defined as all randomized subjects who received at least one dose of study drug and had participated in the study for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 113 120
Measure Type: Number
Unit of Measure: participants
10 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation
Hide Description Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy.
Time Frame 100 days post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-M population, defined as all randomized subjects who received at least one dose of study drug and had participated in the study for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 113 120
Measure Type: Number
Unit of Measure: participants
pp65 antigenemia assay 49 19
CMV DNA PCR assay 59 18
pp65 antigenemia or CMV DNA PCR assay 68 24
Initiation of anti-CMV therapy 37 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of pp65 antigenemia assay
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.041
Confidence Interval (2-Sided) 95%
2.179 to 7.494
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of CMV DNA PCR assay
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.448
Confidence Interval (2-Sided) 95%
3.404 to 12.213
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of pp65 antigenemia or CMV DNA PCR assay
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.020
Confidence Interval (2-Sided) 95%
3.342 to 10.843
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maribavir 100 mg BID, Ganciclovir 1000 mg TID
Comments Analysis of initiation of anti-CMV therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is from the Cochran-Mantel-Haenszel test, adjusting for receipt of induction ALA and geographic region (US or Europe).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.165
Confidence Interval (2-Sided) 95%
4.146 to 30.069
Estimation Comments Mantel-Haenszel odds ratio for maribavir versus ganciclovir
7.Secondary Outcome
Title Number of Participants With Retransplantation
Hide Description [Not Specified]
Time Frame Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-Safety (ITT-S) population, defined as all participants who received at least one dose of study drug.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 147 156
Measure Type: Number
Unit of Measure: participants
At 100 days post-transplant 1 2
At 6 months post-transplant 2 2
8.Secondary Outcome
Title Number of Participants With Graft Failure Related Death
Hide Description [Not Specified]
Time Frame Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-S population, defined as all participants who received at least one dose of study drug.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 147 156
Measure Type: Number
Unit of Measure: participants
100 days post-transplant 0 2
6 months post-transplant 1 2
9.Secondary Outcome
Title Number of Participants With Acute Graft Rejection
Hide Description Rejection was assessed by examining a liver biopsy sample. Diagnosis of graft rejection included a global assessment grade and a rejection activity index score.
Time Frame 26 weeks post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-S population, defined as all participants who received at least one dose of study drug.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 147 156
Measure Type: Number
Unit of Measure: participants
100 days post-transplant 16 19
6 months post-transplant 20 23
10.Secondary Outcome
Title Number of Participants Who Died Within 6 Months Post-Transplantation
Hide Description [Not Specified]
Time Frame 6 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-S population, defined as all participants who received at least one dose of study drug.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 147 156
Measure Type: Number
Unit of Measure: participants
9 6
11.Secondary Outcome
Title Percent of Participants With Signs of Bone Marrow Suppression
Hide Description Bone marrow suppression was assessed by the occurrence of adverse events (AEs) of investigator-reported leukopenia, neutropenia, thrombocytopenia, and pancytopenia; absolute neutrophil count (ANC) <1000/mm3; white blood cell (WBC) count toxicity grade shifts from 0-2 at baseline to a maximum of 3-4 post-baseline; and use of hematopoietic growth factors during the 6 month post-transplant period.
Time Frame 15 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT-S population, defined as all participants who received at least one dose of study drug.
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Overall Number of Participants Analyzed 147 156
Measure Type: Number
Unit of Measure: percent of participants
Hematology AEs 14 21
ANC <1000/mm3 9 16
WBC count toxicity grade shifts 16 21
Use of hematopoietic growth factors 15 20
12.Secondary Outcome
Title Plasma Concentration of Maribavir During Treatment
Hide Description For the first 16 subjects to have PK profiling performed, PK sampling was collected at Weeks 2, 6 and 10. For subsequent subjects that have PK profiling performed, PK sampling was collected at Weeks 2 and 6. Samples were collected 12 hours after the morning dose of maribavir. Permissible assessment windows for pharmacokinetic profile sampling purposes were +/- 5 days for each sampling day. Samples for determination of maribavir concentration were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. For plasma, the minimum detectable concentration for maribavir was 0.2 μg/mL.
Time Frame 12 hours post-dose after 2, 6, and 10 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) population, defined as those participants in the ITT-S population from whom plasma samples were drawn, tested for maribavir concentrations, and complete, evaluable PK data were available.
Arm/Group Title Maribavir 100 mg BID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: μg/mL
2 weeks, n=10 1.65  (2.01)
6 weeks, n=7 1.36  (1.25)
10 weeks, n=8 1.55  (1.17)
13.Secondary Outcome
Title Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment
Hide Description For the first 16 subjects to have PK profiling performed, PK sampling was collected at Weeks 2, 6 and 10. For subsequent subjects that have PK profiling performed, PK sampling was collected at Weeks 2 and 6. Samples were collected 12 hours after the morning dose of maribavir. Permissible assessment windows for pharmacokinetic profile sampling purposes were +/- 5 days for each sampling day. Samples for determination of VP 44469 (a metabolite of maribavir) concentration were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. For plasma, the minimum detectable concentration for VP 44469 was 0.2 μg/mL.
Time Frame 12 hours post-dose after 2, 6, and 10 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK population, defined as those participants in the ITT-S population from whom plasma samples were drawn, tested for maribavir concentrations, and complete, evaluable PK data were available.
Arm/Group Title Maribavir 100 mg BID
Hide Arm/Group Description:
Maribavir: 100mg twice a day (BID) for 14 weeks.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: μg/mL
2 weeks, n=10 0.609  (0.648)
6 weeks, n=7 0.506  (0.224)
10 weeks, n=8 0.666  (0.656)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Maribavir 100 mg BID Ganciclovir 1000 mg TID
Hide Arm/Group Description Maribavir: 100mg twice a day (BID) for 14 weeks. Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
All-Cause Mortality
Maribavir 100 mg BID Ganciclovir 1000 mg TID
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Maribavir 100 mg BID Ganciclovir 1000 mg TID
Affected / at Risk (%) Affected / at Risk (%)
Total   71/147 (48.30%)   76/156 (48.72%) 
Blood and lymphatic system disorders     
Anaemia  1  1/147 (0.68%)  4/156 (2.56%) 
Haemolytic Anaemia  1  1/147 (0.68%)  1/156 (0.64%) 
Leukocytosis  1  1/147 (0.68%)  0/156 (0.00%) 
Leukopenia  1  0/147 (0.00%)  1/156 (0.64%) 
Neutropenia  1  0/147 (0.00%)  1/156 (0.64%) 
Splenomegaly  1  0/147 (0.00%)  1/156 (0.64%) 
Thrombocytopenia  1  0/147 (0.00%)  1/156 (0.64%) 
Cardiac disorders     
Atrial Fibrillation  1  0/147 (0.00%)  1/156 (0.64%) 
Bradycardia  1  0/147 (0.00%)  1/156 (0.64%) 
Cardiac Failure  1  1/147 (0.68%)  0/156 (0.00%) 
Myocardial Infarction  1  1/147 (0.68%)  2/156 (1.28%) 
Supraventricular Extrasystoles  1  1/147 (0.68%)  0/156 (0.00%) 
Endocrine disorders     
Diabetes Mellitus  1  2/147 (1.36%)  0/156 (0.00%) 
Eye disorders     
Cataract  1  1/147 (0.68%)  0/156 (0.00%) 
Ulcerative Keratitis  1  1/147 (0.68%)  0/156 (0.00%) 
Gastrointestinal disorders     
Abdominal Abscess  1  1/147 (0.68%)  1/156 (0.64%) 
Abdominal Pain  1  1/147 (0.68%)  2/156 (1.28%) 
Abdominal Pain Upper  1  0/147 (0.00%)  1/156 (0.64%) 
Abdominal Strangulated Hernia  1  0/147 (0.00%)  1/156 (0.64%) 
Clostridium Difficile Colitis  1  3/147 (2.04%)  3/156 (1.92%) 
Colitis Ulcerative  1  0/147 (0.00%)  1/156 (0.64%) 
Constipation  1  1/147 (0.68%)  0/156 (0.00%) 
Diarrhoea  1  2/147 (1.36%)  4/156 (2.56%) 
Diverticulitis  1  1/147 (0.68%)  0/156 (0.00%) 
Fungal Peritonitis  1  0/147 (0.00%)  1/156 (0.64%) 
Gastroenteritis  1  0/147 (0.00%)  2/156 (1.28%) 
Ileus  1  1/147 (0.68%)  0/156 (0.00%) 
Inguinal Hernia  1  0/147 (0.00%)  3/156 (1.92%) 
Intra-Abdominal Haemorrhage  1  1/147 (0.68%)  0/156 (0.00%) 
Nausea  1  1/147 (0.68%)  2/156 (1.28%) 
Obstruction Gastric  1  1/147 (0.68%)  0/156 (0.00%) 
Oesophageal Candidiasis  1  1/147 (0.68%)  0/156 (0.00%) 
Oesophagitis  1  0/147 (0.00%)  1/156 (0.64%) 
Pancreatitis  1  0/147 (0.00%)  2/156 (1.28%) 
Peritonitis  1  1/147 (0.68%)  2/156 (1.28%) 
Umbilical Hernia  1  2/147 (1.36%)  1/156 (0.64%) 
Vomiting  1  1/147 (0.68%)  3/156 (1.92%) 
General disorders     
Asthenia  1  0/147 (0.00%)  1/156 (0.64%) 
Non-Cardiac Chest Pain  1  1/147 (0.68%)  0/156 (0.00%) 
Oedema  1  1/147 (0.68%)  0/156 (0.00%) 
Oedema Peripheral  1  2/147 (1.36%)  0/156 (0.00%) 
Pyrexia  1  4/147 (2.72%)  7/156 (4.49%) 
Hepatobiliary disorders     
Alcoholic Liver Disease  1  1/147 (0.68%)  0/156 (0.00%) 
Ascites  1  3/147 (2.04%)  4/156 (2.56%) 
Bile Duct Obstruction  1  0/147 (0.00%)  1/156 (0.64%) 
Bile Duct Stenosis  1  4/147 (2.72%)  2/156 (1.28%) 
Cholangitis  1  3/147 (2.04%)  2/156 (1.28%) 
Cholestasis  1  3/147 (2.04%)  0/156 (0.00%) 
Cytolytic Hepatitis  1  0/147 (0.00%)  1/156 (0.64%) 
Hepatic Artery Aneurysm  1  0/147 (0.00%)  2/156 (1.28%) 
Hepatic Artery Occlusion  1  0/147 (0.00%)  2/156 (1.28%) 
Hepatic Artery Stenosis  1  1/147 (0.68%)  0/156 (0.00%) 
Hepatic Artery Thrombosis  1  1/147 (0.68%)  3/156 (1.92%) 
Hepatic Haematoma  1  1/147 (0.68%)  0/156 (0.00%) 
Hepatic Necrosis  1  0/147 (0.00%)  1/156 (0.64%) 
Hepatic Steatosis  1  0/147 (0.00%)  1/156 (0.64%) 
Hepatitis C  1  2/147 (1.36%)  3/156 (1.92%) 
Liver Abscess  1  1/147 (0.68%)  1/156 (0.64%) 
Portal Hypertension  1  0/147 (0.00%)  1/156 (0.64%) 
Post Procedural Bile Leak  1  4/147 (2.72%)  2/156 (1.28%) 
Immune system disorders     
Acute Graft Versus Host Disease  1  1/147 (0.68%)  1/156 (0.64%) 
Hypersensitivity  1  1/147 (0.68%)  0/156 (0.00%) 
Liver Transplant Rejection  1  4/147 (2.72%)  12/156 (7.69%) 
Infections and infestations     
Abdominal Sepsis  1  0/147 (0.00%)  1/156 (0.64%) 
Bacterial Sepsis  1  0/147 (0.00%)  1/156 (0.64%) 
Cytomegalovirus Gastroenteritis  1  2/147 (1.36%)  1/156 (0.64%) 
Cytomegalovirus Hepatitis  1  2/147 (1.36%)  0/156 (0.00%) 
Cytomegalovirus Infection  1  12/147 (8.16%)  2/156 (1.28%) 
Pneumonia Cytomegaloviral  1  2/147 (1.36%)  0/156 (0.00%) 
Sepsis  1  1/147 (0.68%)  2/156 (1.28%) 
Injury, poisoning and procedural complications     
Complications Of Transplanted Liver  1  1/147 (0.68%)  0/156 (0.00%) 
Fall  1  0/147 (0.00%)  1/156 (0.64%) 
Incision Site Cellulitis  1  0/147 (0.00%)  1/156 (0.64%) 
Incision Site Pain  1  0/147 (0.00%)  1/156 (0.64%) 
Incisional Hernia  1  1/147 (0.68%)  0/156 (0.00%) 
Post Procedural Haemorrhage  1  1/147 (0.68%)  0/156 (0.00%) 
Postoperative Wound Infection  1  0/147 (0.00%)  1/156 (0.64%) 
Therapeutic Agent Toxicity  1  0/147 (0.00%)  1/156 (0.64%) 
Wound Dehiscence  1  0/147 (0.00%)  1/156 (0.64%) 
Wound Infection  1  3/147 (2.04%)  3/156 (1.92%) 
Wound Secretion  1  1/147 (0.68%)  1/156 (0.64%) 
Investigations     
Band Neutrophil Count Increased  1  0/147 (0.00%)  1/156 (0.64%) 
Biopsy Liver Abnormal  1  1/147 (0.68%)  0/156 (0.00%) 
Blood Bilirubin Increased  1  1/147 (0.68%)  1/156 (0.64%) 
Blood Creatinine Increased  1  0/147 (0.00%)  1/156 (0.64%) 
Hepatic Enzyme Increased  1  8/147 (5.44%)  4/156 (2.56%) 
International Normalised Ratio Increased  1  0/147 (0.00%)  1/156 (0.64%) 
Metabolism and nutrition disorders     
Dehydration  1  2/147 (1.36%)  1/156 (0.64%) 
Hyperglycaemia  1  1/147 (0.68%)  0/156 (0.00%) 
Hyperkalaemia  1  1/147 (0.68%)  3/156 (1.92%) 
Hypocalcaemia  1  0/147 (0.00%)  1/156 (0.64%) 
Hypoglycaemia  1  0/147 (0.00%)  1/156 (0.64%) 
Hypomagnesaemia  1  1/147 (0.68%)  0/156 (0.00%) 
Hyponatraemia  1  0/147 (0.00%)  1/156 (0.64%) 
Hypovolaemia  1  0/147 (0.00%)  1/156 (0.64%) 
Musculoskeletal and connective tissue disorders     
Arthritis Fungal  1  0/147 (0.00%)  1/156 (0.64%) 
Femoral Neck Fracture  1  1/147 (0.68%)  0/156 (0.00%) 
Musculoskeletal Chest Pain  1  0/147 (0.00%)  1/156 (0.64%) 
Nervous system disorders     
Cerebral Haemorrhage  1  1/147 (0.68%)  0/156 (0.00%) 
Convulsion  1  1/147 (0.68%)  1/156 (0.64%) 
Dizziness  1  0/147 (0.00%)  1/156 (0.64%) 
Haemorrhage Intracranial  1  1/147 (0.68%)  0/156 (0.00%) 
Hypoglycaemic Seizure  1  0/147 (0.00%)  1/156 (0.64%) 
Psychiatric disorders     
Adjustment Disorder  1  1/147 (0.68%)  0/156 (0.00%) 
Bipolar Disorder  1  1/147 (0.68%)  0/156 (0.00%) 
Confusional State  1  0/147 (0.00%)  1/156 (0.64%) 
Delirium  1  0/147 (0.00%)  2/156 (1.28%) 
Mental Status Changes  1  1/147 (0.68%)  0/156 (0.00%) 
Psychotic Disorder  1  1/147 (0.68%)  1/156 (0.64%) 
Renal and urinary disorders     
Mesangioproliferative Glomerulonephritis  1  1/147 (0.68%)  0/156 (0.00%) 
Nephritis Interstitial  1  0/147 (0.00%)  1/156 (0.64%) 
Nephrolithiasis  1  1/147 (0.68%)  0/156 (0.00%) 
Renal Failure  1  4/147 (2.72%)  3/156 (1.92%) 
Urinary Tract Infection  1  1/147 (0.68%)  1/156 (0.64%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/147 (0.00%)  1/156 (0.64%) 
Lung Neoplasm Malignant  1  0/147 (0.00%)  1/156 (0.64%) 
Pleural Effusion  1  2/147 (1.36%)  3/156 (1.92%) 
Pleural Infection  1  1/147 (0.68%)  0/156 (0.00%) 
Pleuritic Pain  1  0/147 (0.00%)  1/156 (0.64%) 
Pneumonia  1  2/147 (1.36%)  1/156 (0.64%) 
Pneumonia Staphylococcal  1  1/147 (0.68%)  0/156 (0.00%) 
Pulmonary Oedema  1  0/147 (0.00%)  1/156 (0.64%) 
Respiratory Arrest  1  1/147 (0.68%)  0/156 (0.00%) 
Respiratory Distress  1  2/147 (1.36%)  0/156 (0.00%) 
Respiratory Failure  1  1/147 (0.68%)  0/156 (0.00%) 
Respiratory Syncytial Virus Infection  1  0/147 (0.00%)  1/156 (0.64%) 
Upper Respiratory Tract Infection  1  1/147 (0.68%)  0/156 (0.00%) 
Skin and subcutaneous tissue disorders     
Cellulitis  1  1/147 (0.68%)  2/156 (1.28%) 
Rash  1  1/147 (0.68%)  0/156 (0.00%) 
Vascular disorders     
Arterial Haemorrhage  1  0/147 (0.00%)  1/156 (0.64%) 
Deep Vein Thrombosis  1  1/147 (0.68%)  0/156 (0.00%) 
Hypotension  1  1/147 (0.68%)  0/156 (0.00%) 
Syncope  1  0/147 (0.00%)  1/156 (0.64%) 
Thrombophlebitis  1  1/147 (0.68%)  0/156 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Maribavir 100 mg BID Ganciclovir 1000 mg TID
Affected / at Risk (%) Affected / at Risk (%)
Total   127/147 (86.39%)   140/156 (89.74%) 
Blood and lymphatic system disorders     
Anaemia  1  9/147 (6.12%)  13/156 (8.33%) 
Leukocytosis  1  8/147 (5.44%)  5/156 (3.21%) 
Leukopenia  1  12/147 (8.16%)  19/156 (12.18%) 
Neutropenia  1  8/147 (5.44%)  10/156 (6.41%) 
Gastrointestinal disorders     
Abdominal Distension  1  0/147 (0.00%)  8/156 (5.13%) 
Abdominal Pain  1  12/147 (8.16%)  15/156 (9.62%) 
Abdominal Pain Upper  1  7/147 (4.76%)  8/156 (5.13%) 
Constipation  1  9/147 (6.12%)  11/156 (7.05%) 
Diarrhoea  1  41/147 (27.89%)  36/156 (23.08%) 
Dysgeusia  1  22/147 (14.97%)  20/156 (12.82%) 
Nausea  1  14/147 (9.52%)  28/156 (17.95%) 
Vomiting  1  14/147 (9.52%)  15/156 (9.62%) 
General disorders     
Asthenia  1  1/147 (0.68%)  8/156 (5.13%) 
Fatigue  1  10/147 (6.80%)  18/156 (11.54%) 
Oedema Peripheral  1  19/147 (12.93%)  15/156 (9.62%) 
Pyrexia  1  15/147 (10.20%)  13/156 (8.33%) 
Hepatobiliary disorders     
Ascites  1  9/147 (6.12%)  7/156 (4.49%) 
Bile Duct Stenosis  1  9/147 (6.12%)  9/156 (5.77%) 
Hepatitis C  1  14/147 (9.52%)  7/156 (4.49%) 
Immune system disorders     
Liver Transplant Rejection  1  11/147 (7.48%)  8/156 (5.13%) 
Investigations     
Hepatic Enzyme Increased  1  16/147 (10.88%)  13/156 (8.33%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  14/147 (9.52%)  6/156 (3.85%) 
Hyperkalaemia  1  19/147 (12.93%)  21/156 (13.46%) 
Hypokalaemia  1  8/147 (5.44%)  4/156 (2.56%) 
Hypomagnesaemia  1  14/147 (9.52%)  12/156 (7.69%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/147 (2.72%)  8/156 (5.13%) 
Back Pain  1  13/147 (8.84%)  11/156 (7.05%) 
Muscle Spasms  1  3/147 (2.04%)  8/156 (5.13%) 
Nervous system disorders     
Dizziness  1  3/147 (2.04%)  12/156 (7.69%) 
Headache  1  20/147 (13.61%)  29/156 (18.59%) 
Insomnia  1  13/147 (8.84%)  17/156 (10.90%) 
Tremor  1  25/147 (17.01%)  20/156 (12.82%) 
Psychiatric disorders     
Anxiety  1  11/147 (7.48%)  4/156 (2.56%) 
Renal and urinary disorders     
Renal Failure  1  12/147 (8.16%)  11/156 (7.05%) 
Urinary Tract Infection  1  22/147 (14.97%)  11/156 (7.05%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  5/147 (3.40%)  9/156 (5.77%) 
Pleural Effusion  1  9/147 (6.12%)  7/156 (4.49%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  9/147 (6.12%)  12/156 (7.69%) 
Rash  1  8/147 (5.44%)  7/156 (4.49%) 
Vascular disorders     
Hypertension  1  18/147 (12.24%)  21/156 (13.46%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 10.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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 Physician
Organization: Shire Development LLC
Phone: +1 866 842 5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00497796     History of Changes
Other Study ID Numbers: 1263-301
2007-004729-16 ( EudraCT Number )
SHP620-301 ( Other Identifier: Shire )
First Submitted: July 5, 2007
First Posted: July 9, 2007
Results First Submitted: May 4, 2015
Results First Posted: June 4, 2015
Last Update Posted: June 4, 2015