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

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00497796
• Collaborator: (none)
• Enrollment: 307
• Locations: 55
• Arms: 2
• Actual Duration (Months): 25.8
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to investigate whether or not oral maribavir is safe and effective compared to oral ganciclovir for preventing CMV disease when administered for up to 14 weeks in patients who have had a liver transplant.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infections	Drug: maribavir; Drug: ganciclovir	Phase 3

Detailed Description

Cytomegalovirus (CMV) infections remain a significant problem following various types of transplants that are associated with strong immunosuppressive therapy. Maribavir is a new oral anti-CMV drug with a novel mechanism of action compared to currently available anti-CMV drugs. This study will test the safety and efficacy of maribavir for the prevention of CMV disease when given as prophylaxis for up to 14 weeks following orthotopic liver transplantation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 307 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-blind Study To Assess The Efficacy And Safety Of Prophylactic Use Of Maribavir Versus Oral Ganciclovir For The Prevention Of Cytomegalovirus Disease In Recipients Of Orthotopic Liver Transplants
• Actual Study Start Date: Jul 23, 2007
• Actual Primary Completion Date: Sep 14, 2009
• Actual Study Completion Date: Sep 14, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: maribavir; 100mg twice a day for 14 weeks.
Active Comparator: 2	Drug: ganciclovir; 1000mg three times per day for 14 weeks.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation [6 months post-transplant]

   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.

Secondary Outcome Measures

1. Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation [6 months post-transplant]

   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.

2. Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation [6 months post-transplant]

   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.

3. Number of Participants With Investigator-determined CMV Disease [Through 6 months post-transplant (Day 1 to 100 days and 6 months post-transplant)]

   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.

4. Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation [100 days post-transplant]

   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.

5. Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation [100 days post-transplant]

   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.

6. Number of Participants With Retransplantation [Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)]

7. Number of Participants With Graft Failure Related Death [Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)]

8. Number of Participants With Acute Graft Rejection [26 weeks post-transplant]

   Rejection was assessed by examining a liver biopsy sample. Diagnosis of graft rejection included a global assessment grade and a rejection activity index score.

9. Number of Participants Who Died Within 6 Months Post-Transplantation [6 months post-transplant]

10. Percent of Participants With Signs of Bone Marrow Suppression [15 weeks]

    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.

11. Plasma Concentration of Maribavir During Treatment [12 hours post-dose after 2, 6, and 10 weeks of treatment]

    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.

12. Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment [12 hours post-dose after 2, 6, and 10 weeks of treatment]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Orthotopic liver transplant recipient

• Donor CMV seropositive / Recipient CMV seronegative

• Enrolled within 10 days after liver transplant

• Able to swallow tablets

Exclusion Criteria:

• Multiple organ transplant

• HIV infection

• CMV disease

• Use of other anti-CMV therapy at time of enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Phoenix	Arizona	United States	85006
2	University of California at San Diego	La Jolla	California	United States	92103
3	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
4	UCLA Medical Center	Los Angeles	California	United States	90095
5	University of California at San Francisco	San Francisco	California	United States	94143
6	Stanford University Medical Center	Stanford	California	United States	94305
7	University of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
8	Georgetown University	Washington	District of Columbia	United States	20007
9	Mayo Clinic College of Medicine	Jacksonville	Florida	United States	32224
10	Tampa General	Tampa	Florida	United States	33606
11	Emory University	Atlanta	Georgia	United States	30322
12	Northwestern University Medical Center	Chicago	Illinois	United States	60611
13	Rush University Medical Center	Chicago	Illinois	United States	60612
14	University of Illinois at Chicago	Chicago	Illinois	United States	60612
15	University of Chicago Medical Center	Chicago	Illinois	United States	60637
16	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
17	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
18	University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536
19	Jewish Hospital Louisville	Louisville	Kentucky	United States	40202
20	Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112
21	Ochsner Clinic	New Orleans	Louisiana	United States	70121
22	New England Medical Center	Boston	Massachusetts	United States	02111
23	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
24	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
25	Lahey Clinic	Burlington	Massachusetts	United States	01805
26	University of Michigan	Ann Arbor	Michigan	United States	48109
27	Henry Ford Health System	Detroit	Michigan	United States	48202
28	University of Minnesota	Minneapolis	Minnesota	United States	55455
29	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
30	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
31	University of Nebraska	Omaha	Nebraska	United States	68198
32	University of Medicine and Dentistry of New Jersey	Newark	New Jersey	United States	07101
33	NYU School of Medicine	New York	New York	United States	10016
34	Columbia University Medical Center	New York	New York	United States	10032
35	University of Rochester Medical Center- Strong Memorial	Rochester	New York	United States	14642
36	New York Medical College	Valhalla	New York	United States	10595
37	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina	United States	27599
38	Duke University Medical Center	Durham	North Carolina	United States	27710
39	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
40	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
41	Integris Baptist Medical Center	Oklahoma City	Oklahoma	United States	73112
42	Oregon Health and Sciences University	Portland	Oregon	United States	97239
43	University of Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19104
44	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15240
45	Medical University of South Carolina	Charleston	South Carolina	United States	29425
46	Methodist Transplant Institute	Memphis	Tennessee	United States	38104
47	Baylor University Medical Center (Dallas)	Dallas	Texas	United States	75246
48	Baylor College of Medicine (Houston)	Houston	Texas	United States	77030
49	Methodist Hospital	Houston	Texas	United States	77030
50	UT Memorial Hermann Hospital and Texas Liver Center	Houston	Texas	United States	77030
51	University of Texas Health Sciences Center at San Antonio	San Antonio	Texas	United States	78229
52	University of Virginia Health System	Charlottesville	Virginia	United States	22908
53	Virginia Commonwealth University	Richmond	Virginia	United States	23298
54	Univeristy of Washington Medical Center	Seattle	Washington	United States	98195-7110
55	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

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: NCT00497796
• Other Study ID Numbers: 1263-301; 2007-004729-16; SHP620-301
• First Posted: Jul 9, 2007
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Shire: cytomegalovirus; CMV; prophylaxis; liver; liver transplant
• Additional relevant MeSH terms: Cytomegalovirus Infections; Ganciclovir; Ganciclovir triphosphate; Maribavir

Study Results

Participant Flow

Arm/Group Title	Maribavir 100 mg BID	Ganciclovir 1000 mg TID
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

Baseline Characteristics

Arm/Group Title	Maribavir 100 mg BID	Ganciclovir 1000 mg TID	Total
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 Participants	147	156	303
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (9.0)	53 (8.9)	54 (9.0)
Sex: Female, Male (Count of Participants)
Female	27 18.4%	37 23.7%	64 21.1%
Male	120 81.6%	119 76.3%	239 78.9%
Distribution of age (Count of Participants)
18 to 44 years	19 12.9%	22 14.1%	41 13.5%
45 to 64 years	109 74.1%	123 78.8%	232 76.6%
65 to 75 years	19 12.9%	11 7.1%	30 9.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	113	120
Number [number of participants with event]	14 9.5%	10 6.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maribavir 100 mg BID, Ganciclovir 1000 mg TID
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	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).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	0.041
	Confidence Interval	(2-Sided) 95%; -0.038 to 0.119
	Parameter Dispersion	Type: Value:
	Estimation Comments	Rate difference is the rate of maribavir minus the rate of ganciclovir

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maribavir 100 mg BID, Ganciclovir 1000 mg TID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.586
	Confidence Interval	(2-Sided) 95%; 0.682 to 3.690
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	113	120
pp65 antigenemia assay	63 42.9%	49 31.4%
CMV DNA PCR assay	72 49%	52 33.3%
pp65 antigenemia or CMV DNA PCR assay	81 55.1%	64 41%
Initiation of anti-CMV therapy	46 31.3%	39 25%

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 (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.793
	Confidence Interval	(2-Sided) 95%; 1.065 to 3.020
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus ganciclovir

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 (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus ganciclovir

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 (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.177
	Confidence Interval	(2-Sided) 95%; 1.259 to 3.767
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus ganciclovir

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 (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.388
	Confidence Interval	(2-Sided) 95%; 0.811 to 2.377
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	113	120
Median (Inter-Quartile Range) [days]	45	127

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 (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Adjusted Hazard Ratio
	Estimated Value	2.25
	Confidence Interval	(2-Sided) 95%; 1.62 to 3.14
	Parameter Dispersion	Type: Value:
	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
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)

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	113	120
100 days post-transplant	17 11.6%	3 1.9%
6 months post-transplant	22 15%	18 11.5%

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 (legacy)
	Comments
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

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 (legacy)
	Comments
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

5. Secondary Outcome

Title	Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	113	120
Number [participants]	10 6.8%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maribavir 100 mg BID, Ganciclovir 1000 mg TID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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

6. Secondary Outcome

Title	Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	113	120
pp65 antigenemia assay	49 33.3%	19 12.2%
CMV DNA PCR assay	59 40.1%	18 11.5%
pp65 antigenemia or CMV DNA PCR assay	68 46.3%	24 15.4%
Initiation of anti-CMV therapy	37 25.2%	5 3.2%

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 (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.041
	Confidence Interval	(2-Sided) 95%; 2.179 to 7.494
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus ganciclovir

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 (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.448
	Confidence Interval	(2-Sided) 95%; 3.404 to 12.213
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus ganciclovir

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 (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.020
	Confidence Interval	(2-Sided) 95%; 3.342 to 10.843
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus ganciclovir

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 (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.165
	Confidence Interval	(2-Sided) 95%; 4.146 to 30.069
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus ganciclovir

7. Secondary Outcome

Title	Number of Participants With Retransplantation
Time Frame	Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	147	156
At 100 days post-transplant	1 0.7%	2 1.3%
At 6 months post-transplant	2 1.4%	2 1.3%

8. Secondary Outcome

Title	Number of Participants With Graft Failure Related Death
Time Frame	Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	147	156
100 days post-transplant	0 0%	2 1.3%
6 months post-transplant	1 0.7%	2 1.3%

9. Secondary Outcome

Title	Number of Participants With Acute Graft Rejection
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	147	156
100 days post-transplant	16 10.9%	19 12.2%
6 months post-transplant	20 13.6%	23 14.7%

10. Secondary Outcome

Title	Number of Participants Who Died Within 6 Months Post-Transplantation
Time Frame	6 months post-transplant

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	147	156
Number [participants]	9 6.1%	6 3.8%

11. Secondary Outcome

Title	Percent of Participants With Signs of Bone Marrow Suppression
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.	Ganciclovir: 1000mg three times per (TID) day for 14 weeks.
Measure Participants	147	156
Hematology AEs	14 9.5%	21 13.5%
ANC <1000/mm3	9 6.1%	16 10.3%
WBC count toxicity grade shifts	16 10.9%	21 13.5%
Use of hematopoietic growth factors	15 10.2%	20 12.8%

12. Secondary Outcome

Title	Plasma Concentration of Maribavir During Treatment
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.
Measure Participants	11
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
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

Outcome Measure Data

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
Arm/Group Description	Maribavir: 100mg twice a day (BID) for 14 weeks.
Measure Participants	11
2 weeks, n=10	0.609 (0.648)
6 weeks, n=7	0.506 (0.224)
10 weeks, n=8	0.666 (0.656)

Adverse Events

Arm/Group Title	Maribavir 100 mg BID		Ganciclovir 1000 mg TID
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Maribavir 100 mg BID		Ganciclovir 1000 mg TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/147 (48.3%)		76/156 (48.7%)
Blood and lymphatic system disorders
Anaemia	1/147 (0.7%)		4/156 (2.6%)
Haemolytic Anaemia	1/147 (0.7%)		1/156 (0.6%)
Leukocytosis	1/147 (0.7%)		0/156 (0%)
Leukopenia	0/147 (0%)		1/156 (0.6%)
Neutropenia	0/147 (0%)		1/156 (0.6%)
Splenomegaly	0/147 (0%)		1/156 (0.6%)
Thrombocytopenia	0/147 (0%)		1/156 (0.6%)
Cardiac disorders
Atrial Fibrillation	0/147 (0%)		1/156 (0.6%)
Bradycardia	0/147 (0%)		1/156 (0.6%)
Cardiac Failure	1/147 (0.7%)		0/156 (0%)
Myocardial Infarction	1/147 (0.7%)		2/156 (1.3%)
Supraventricular Extrasystoles	1/147 (0.7%)		0/156 (0%)
Endocrine disorders
Diabetes Mellitus	2/147 (1.4%)		0/156 (0%)
Eye disorders
Cataract	1/147 (0.7%)		0/156 (0%)
Ulcerative Keratitis	1/147 (0.7%)		0/156 (0%)
Gastrointestinal disorders
Abdominal Abscess	1/147 (0.7%)		1/156 (0.6%)
Abdominal Pain	1/147 (0.7%)		2/156 (1.3%)
Abdominal Pain Upper	0/147 (0%)		1/156 (0.6%)
Abdominal Strangulated Hernia	0/147 (0%)		1/156 (0.6%)
Clostridium Difficile Colitis	3/147 (2%)		3/156 (1.9%)
Colitis Ulcerative	0/147 (0%)		1/156 (0.6%)
Constipation	1/147 (0.7%)		0/156 (0%)
Diarrhoea	2/147 (1.4%)		4/156 (2.6%)
Diverticulitis	1/147 (0.7%)		0/156 (0%)
Fungal Peritonitis	0/147 (0%)		1/156 (0.6%)
Gastroenteritis	0/147 (0%)		2/156 (1.3%)
Ileus	1/147 (0.7%)		0/156 (0%)
Inguinal Hernia	0/147 (0%)		3/156 (1.9%)
Intra-Abdominal Haemorrhage	1/147 (0.7%)		0/156 (0%)
Nausea	1/147 (0.7%)		2/156 (1.3%)
Obstruction Gastric	1/147 (0.7%)		0/156 (0%)
Oesophageal Candidiasis	1/147 (0.7%)		0/156 (0%)
Oesophagitis	0/147 (0%)		1/156 (0.6%)
Pancreatitis	0/147 (0%)		2/156 (1.3%)
Peritonitis	1/147 (0.7%)		2/156 (1.3%)
Umbilical Hernia	2/147 (1.4%)		1/156 (0.6%)
Vomiting	1/147 (0.7%)		3/156 (1.9%)
General disorders
Asthenia	0/147 (0%)		1/156 (0.6%)
Non-Cardiac Chest Pain	1/147 (0.7%)		0/156 (0%)
Oedema	1/147 (0.7%)		0/156 (0%)
Oedema Peripheral	2/147 (1.4%)		0/156 (0%)
Pyrexia	4/147 (2.7%)		7/156 (4.5%)
Hepatobiliary disorders
Alcoholic Liver Disease	1/147 (0.7%)		0/156 (0%)
Ascites	3/147 (2%)		4/156 (2.6%)
Bile Duct Obstruction	0/147 (0%)		1/156 (0.6%)
Bile Duct Stenosis	4/147 (2.7%)		2/156 (1.3%)
Cholangitis	3/147 (2%)		2/156 (1.3%)
Cholestasis	3/147 (2%)		0/156 (0%)
Cytolytic Hepatitis	0/147 (0%)		1/156 (0.6%)
Hepatic Artery Aneurysm	0/147 (0%)		2/156 (1.3%)
Hepatic Artery Occlusion	0/147 (0%)		2/156 (1.3%)
Hepatic Artery Stenosis	1/147 (0.7%)		0/156 (0%)
Hepatic Artery Thrombosis	1/147 (0.7%)		3/156 (1.9%)
Hepatic Haematoma	1/147 (0.7%)		0/156 (0%)
Hepatic Necrosis	0/147 (0%)		1/156 (0.6%)
Hepatic Steatosis	0/147 (0%)		1/156 (0.6%)
Hepatitis C	2/147 (1.4%)		3/156 (1.9%)
Liver Abscess	1/147 (0.7%)		1/156 (0.6%)
Portal Hypertension	0/147 (0%)		1/156 (0.6%)
Post Procedural Bile Leak	4/147 (2.7%)		2/156 (1.3%)
Immune system disorders
Acute Graft Versus Host Disease	1/147 (0.7%)		1/156 (0.6%)
Hypersensitivity	1/147 (0.7%)		0/156 (0%)
Liver Transplant Rejection	4/147 (2.7%)		12/156 (7.7%)
Infections and infestations
Abdominal Sepsis	0/147 (0%)		1/156 (0.6%)
Bacterial Sepsis	0/147 (0%)		1/156 (0.6%)
Cytomegalovirus Gastroenteritis	2/147 (1.4%)		1/156 (0.6%)
Cytomegalovirus Hepatitis	2/147 (1.4%)		0/156 (0%)
Cytomegalovirus Infection	12/147 (8.2%)		2/156 (1.3%)
Pneumonia Cytomegaloviral	2/147 (1.4%)		0/156 (0%)
Sepsis	1/147 (0.7%)		2/156 (1.3%)
Injury, poisoning and procedural complications
Complications Of Transplanted Liver	1/147 (0.7%)		0/156 (0%)
Fall	0/147 (0%)		1/156 (0.6%)
Incision Site Cellulitis	0/147 (0%)		1/156 (0.6%)
Incision Site Pain	0/147 (0%)		1/156 (0.6%)
Incisional Hernia	1/147 (0.7%)		0/156 (0%)
Post Procedural Haemorrhage	1/147 (0.7%)		0/156 (0%)
Postoperative Wound Infection	0/147 (0%)		1/156 (0.6%)
Therapeutic Agent Toxicity	0/147 (0%)		1/156 (0.6%)
Wound Dehiscence	0/147 (0%)		1/156 (0.6%)
Wound Infection	3/147 (2%)		3/156 (1.9%)
Wound Secretion	1/147 (0.7%)		1/156 (0.6%)
Investigations
Band Neutrophil Count Increased	0/147 (0%)		1/156 (0.6%)
Biopsy Liver Abnormal	1/147 (0.7%)		0/156 (0%)
Blood Bilirubin Increased	1/147 (0.7%)		1/156 (0.6%)
Blood Creatinine Increased	0/147 (0%)		1/156 (0.6%)
Hepatic Enzyme Increased	8/147 (5.4%)		4/156 (2.6%)
International Normalised Ratio Increased	0/147 (0%)		1/156 (0.6%)
Metabolism and nutrition disorders
Dehydration	2/147 (1.4%)		1/156 (0.6%)
Hyperglycaemia	1/147 (0.7%)		0/156 (0%)
Hyperkalaemia	1/147 (0.7%)		3/156 (1.9%)
Hypocalcaemia	0/147 (0%)		1/156 (0.6%)
Hypoglycaemia	0/147 (0%)		1/156 (0.6%)
Hypomagnesaemia	1/147 (0.7%)		0/156 (0%)
Hyponatraemia	0/147 (0%)		1/156 (0.6%)
Hypovolaemia	0/147 (0%)		1/156 (0.6%)
Musculoskeletal and connective tissue disorders
Arthritis Fungal	0/147 (0%)		1/156 (0.6%)
Femoral Neck Fracture	1/147 (0.7%)		0/156 (0%)
Musculoskeletal Chest Pain	0/147 (0%)		1/156 (0.6%)
Nervous system disorders
Cerebral Haemorrhage	1/147 (0.7%)		0/156 (0%)
Convulsion	1/147 (0.7%)		1/156 (0.6%)
Dizziness	0/147 (0%)		1/156 (0.6%)
Haemorrhage Intracranial	1/147 (0.7%)		0/156 (0%)
Hypoglycaemic Seizure	0/147 (0%)		1/156 (0.6%)
Psychiatric disorders
Adjustment Disorder	1/147 (0.7%)		0/156 (0%)
Bipolar Disorder	1/147 (0.7%)		0/156 (0%)
Confusional State	0/147 (0%)		1/156 (0.6%)
Delirium	0/147 (0%)		2/156 (1.3%)
Mental Status Changes	1/147 (0.7%)		0/156 (0%)
Psychotic Disorder	1/147 (0.7%)		1/156 (0.6%)
Renal and urinary disorders
Mesangioproliferative Glomerulonephritis	1/147 (0.7%)		0/156 (0%)
Nephritis Interstitial	0/147 (0%)		1/156 (0.6%)
Nephrolithiasis	1/147 (0.7%)		0/156 (0%)
Renal Failure	4/147 (2.7%)		3/156 (1.9%)
Urinary Tract Infection	1/147 (0.7%)		1/156 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/147 (0%)		1/156 (0.6%)
Lung Neoplasm Malignant	0/147 (0%)		1/156 (0.6%)
Pleural Effusion	2/147 (1.4%)		3/156 (1.9%)
Pleural Infection	1/147 (0.7%)		0/156 (0%)
Pleuritic Pain	0/147 (0%)		1/156 (0.6%)
Pneumonia	2/147 (1.4%)		1/156 (0.6%)
Pneumonia Staphylococcal	1/147 (0.7%)		0/156 (0%)
Pulmonary Oedema	0/147 (0%)		1/156 (0.6%)
Respiratory Arrest	1/147 (0.7%)		0/156 (0%)
Respiratory Distress	2/147 (1.4%)		0/156 (0%)
Respiratory Failure	1/147 (0.7%)		0/156 (0%)
Respiratory Syncytial Virus Infection	0/147 (0%)		1/156 (0.6%)
Upper Respiratory Tract Infection	1/147 (0.7%)		0/156 (0%)
Skin and subcutaneous tissue disorders
Cellulitis	1/147 (0.7%)		2/156 (1.3%)
Rash	1/147 (0.7%)		0/156 (0%)
Vascular disorders
Arterial Haemorrhage	0/147 (0%)		1/156 (0.6%)
Deep Vein Thrombosis	1/147 (0.7%)		0/156 (0%)
Hypotension	1/147 (0.7%)		0/156 (0%)
Syncope	0/147 (0%)		1/156 (0.6%)
Thrombophlebitis	1/147 (0.7%)		0/156 (0%)
Other (Not Including Serious) Adverse Events
	Maribavir 100 mg BID		Ganciclovir 1000 mg TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	127/147 (86.4%)		140/156 (89.7%)
Blood and lymphatic system disorders
Anaemia	9/147 (6.1%)		13/156 (8.3%)
Leukocytosis	8/147 (5.4%)		5/156 (3.2%)
Leukopenia	12/147 (8.2%)		19/156 (12.2%)
Neutropenia	8/147 (5.4%)		10/156 (6.4%)
Gastrointestinal disorders
Abdominal Distension	0/147 (0%)		8/156 (5.1%)
Abdominal Pain	12/147 (8.2%)		15/156 (9.6%)
Abdominal Pain Upper	7/147 (4.8%)		8/156 (5.1%)
Constipation	9/147 (6.1%)		11/156 (7.1%)
Diarrhoea	41/147 (27.9%)		36/156 (23.1%)
Dysgeusia	22/147 (15%)		20/156 (12.8%)
Nausea	14/147 (9.5%)		28/156 (17.9%)
Vomiting	14/147 (9.5%)		15/156 (9.6%)
General disorders
Asthenia	1/147 (0.7%)		8/156 (5.1%)
Fatigue	10/147 (6.8%)		18/156 (11.5%)
Oedema Peripheral	19/147 (12.9%)		15/156 (9.6%)
Pyrexia	15/147 (10.2%)		13/156 (8.3%)
Hepatobiliary disorders
Ascites	9/147 (6.1%)		7/156 (4.5%)
Bile Duct Stenosis	9/147 (6.1%)		9/156 (5.8%)
Hepatitis C	14/147 (9.5%)		7/156 (4.5%)
Immune system disorders
Liver Transplant Rejection	11/147 (7.5%)		8/156 (5.1%)
Investigations
Hepatic Enzyme Increased	16/147 (10.9%)		13/156 (8.3%)
Metabolism and nutrition disorders
Decreased Appetite	14/147 (9.5%)		6/156 (3.8%)
Hyperkalaemia	19/147 (12.9%)		21/156 (13.5%)
Hypokalaemia	8/147 (5.4%)		4/156 (2.6%)
Hypomagnesaemia	14/147 (9.5%)		12/156 (7.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/147 (2.7%)		8/156 (5.1%)
Back Pain	13/147 (8.8%)		11/156 (7.1%)
Muscle Spasms	3/147 (2%)		8/156 (5.1%)
Nervous system disorders
Dizziness	3/147 (2%)		12/156 (7.7%)
Headache	20/147 (13.6%)		29/156 (18.6%)
Insomnia	13/147 (8.8%)		17/156 (10.9%)
Tremor	25/147 (17%)		20/156 (12.8%)
Psychiatric disorders
Anxiety	11/147 (7.5%)		4/156 (2.6%)
Renal and urinary disorders
Renal Failure	12/147 (8.2%)		11/156 (7.1%)
Urinary Tract Infection	22/147 (15%)		11/156 (7.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/147 (3.4%)		9/156 (5.8%)
Pleural Effusion	9/147 (6.1%)		7/156 (4.5%)
Skin and subcutaneous tissue disorders
Pruritus	9/147 (6.1%)		12/156 (7.7%)
Rash	8/147 (5.4%)		7/156 (4.5%)
Vascular disorders
Hypertension	18/147 (12.2%)		21/156 (13.5%)

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.