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A Study on Spermatogenesis in Male Renal Transplant Recipients Receiving Valganciclovir (Valcyte®) Versus Untreated Matched Controls

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01663740
Collaborator
(none)
59
Enrollment
19
Locations
2
Arms
59
Actual Duration (Months)
3.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This observational study will compare spermatogenesis in male adult renal transplant recipients receiving valganciclovir versus untreated matched controls. Data will be collected from each participant for up to 52 weeks post transplant.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
59 participants
Allocation:
Randomized
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Multicenter Prospective Cohort Study to Investigate if Ganciclovir Significantly Affects Spermatogenesis in Adult Male Renal Transplant Recipients Receiving up to 200 Days Valganciclovir Vs. Concurrent Untreated Matched Controls
Actual Study Start Date :
Jan 30, 2012
Actual Primary Completion Date :
Sep 29, 2015
Actual Study Completion Date :
Dec 30, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort A: Partcipants who Received Valganciclovir

Participants with donor positive (D+)/recipient negative (R-) cytomegalovirus (CMV) serology, who receive valganciclovir prophylaxis according to the local prescribing information, will be observed for spermatogenesis up to 52 weeks post-transplant.

Drug: Valganciclovir
Participants will receive valganciclovir 900 milligrams (mg) orally once daily for up to a maximum of 200 days post-transplant.
Other Names:
  • Valcyte®

    		•
    No Intervention: Cohort B: Untreated Participants

    Participants with donor negative (D-)/R- CMV serology, who do not receive prophylaxis, will be observed for spermatogenesis up to 52 weeks post-transplant.

    Outcome Measures

    Primary Outcome Measures

    1. Change in Sperm Density From Baseline to the End of Treatment (EOT) [Baseline, EOT (Week 28)]

      Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (EOT) minus (-) the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).

    Secondary Outcome Measures

    1. Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU) [Baseline, EOT (Week 28), end of FU (Week 52)]

      Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at post-baseline visit (EOT and FU) minus the TUNEL score measured at baseline for each participant. A negative change from baseline indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0 percent (%) to 100%, higher score represents more fragmentation.

    2. Change in TUNEL Score From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at FU minus the TUNEL score measured at EOT for each participant. A negative change from EOT indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0% to 100%, higher score represents more fragmentation.

    3. Change in Seminal Volume From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at post-baseline visit (EOT and FU) - the seminal volume measured at baseline for each participant. A negative change from baseline indicated a lower seminal volume (worsening).

    4. Change in Seminal Volume From EOT to End FU [EOT (Week 28), end of FU (Week 52)]

      Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at FU - the seminal volume measured at EOT for each participant. A negative change from EOT indicated a lower seminal volume (worsening).

    5. Change in Sperm Density From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at FU - the sperm density measured at EOT for each participant. A negative change from EOT indicated a lower sperm density (worsening).

    6. Change in Sperm Density From Baseline to End of FU [Baseline, end of FU (Week 52)]

      Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (FU) - the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).

    7. Change in Total Motility of Sperm From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at post-baseline visit (EOT and FU) - the sperm motility measured at baseline for each participant. A negative change from baseline indicated a lower sperm motility (worsening).

    8. Change in Total Motility of Sperm From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at FU - the sperm motility measured at EOT for each participant. A negative change from EOT indicated a lower sperm motility (worsening).

    9. Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at post-baseline visit (EOT and FU) - the sperm morphology measured at baseline for each participant. A positive change from baseline indicated an improved sperm morphology.

    10. Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at FU - the sperm morphology measured at EOT for each participant. A positive change from EOT indicated an improved sperm morphology.

    11. Change in Total Testosterone Level From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at post-baseline visit (EOT and FU) - the testosterone level measured at baseline for each participant. A negative change from baseline indicated a lower testosterone level.

    12. Change in Total Testosterone Level From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at FU - the testosterone level measured at EOT for each participant. A negative change from EOT indicated a lower testosterone level.

    13. Change in LH Level From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at post-baseline visit (EOT and FU) - the LH level measured at baseline for each participant. A negative change from baseline indicated a lower LH level.

    14. Change in LH Level From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at FU - the LH level measured at EOT for each participant. A negative change from EOT indicated a lower LH level.

    15. Change in FSH Level From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at post-baseline visit (EOT and FU) - the FSH level measured at baseline for each participant. A negative change from baseline indicated a lower FSH level.

    16. Change in FSH Level From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at FU - the FSH level measured at EOT for each participant. A negative change from EOT indicated a lower FSH level.

    17. Change in Prolactin Level From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at post-baseline visit (EOT and FU) - the prolactin level measured at baseline for each participant. A negative change from baseline indicated a lower prolactin level.

    18. Change in Prolactin Level From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at FU - the prolactin level measured at EOT for each participant. A negative change from EOT indicated a lower prolactin level.

    19. Change in Inhibin B Level From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at post-baseline visit (EOT and FU) - the inhibin B level measured at baseline for each participant. A negative change from baseline indicated a lower inhibin B level.

    20. Change in Inhibin B Level From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at FU - the inhibin B level measured at EOT for each participant. A negative change from EOT indicated a lower inhibin B level.

    21. Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Abnormal sperm density was considered as sperm density less than (<) 20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from baseline to EOT and end of FU was reported.

    22. Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Abnormal sperm density was considered as sperm density <20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from EOT to end of FU was reported.

    23. Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.

    24. Percentage of Participants With Improved TUNEL Score From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.

    25. Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU [Baseline, EOT (Week 28), end of FU (Week 52)]

      Participants who had higher sperm density compared with the previous visit were considered as improved.

    26. Percentage of Participants With Improved Sperm Density From EOT to End of FU [EOT (Week 28), end of FU (Week 52)]

      Participants who had higher sperm density compared with the previous visit were considered as improved.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 50 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • First renal transplant

    • Participant eligible to receive valganciclovir prophylaxis as determined by the treating physician in accordance with the local approved product prescribing information (Cohort A only) or the participant is not expected to require any valganciclovir prophylaxis (Cohort B only) post-transplant

    • Participant has no history of known infertility

    • Participant is able and willing to provide semen samples

    • Participant agrees to utilize a barrier contraceptive throughout the study or for at least 90 days after cessation of valganciclovir treatment

    Exclusion Criteria:

    • Prior ganciclovir or valganciclovir within 3 months of enrollment

    • Organ transplant other than kidney

    • Participant has received an investigational new drug in the 3 months prior to transplant

    • Participant hs received an alkylating agent or other medications known to affect fertility/spermatogenesis

    • Participant is unlikely to be available for follow-up for the entire duration of the study (up to 52 weeks)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institute of Transplantation Los Angeles California United States 90057
    2 University of California Los Angeles (UCLA) Los Angeles California United States 90095
    3 University of California at San Francisco San Francisco California United States 94115
    4 Washington Hospital Center Washington District of Columbia United States 20010
    5 Medical College of Georgia Augusta Georgia United States 30912
    6 Tufts Medical Center Boston Massachusetts United States 02111
    7 Western New England Renal & Transplant Associates, P.C. Springfield Massachusetts United States 01107
    8 University of Minnesota Minneapolis Minnesota United States 55455
    9 Mayo Clinic Rochester Rochester Minnesota United States 55902
    10 Albany Medical Cancer Center Albany New York United States 12208
    11 University at Buffalo Buffalo New York United States 14203
    12 Stony Brook University Hospital Stony Brook New York United States 11794
    13 Oregan Health & Science Univ Portland Oregon United States 97237
    14 Drexel University Department of Nephrology Philadelphia Pennsylvania United States 19102
    15 Rhode Island Hospital Providence Rhode Island United States 02903
    16 Methodist Healthcare System of San Antonio San Antonio Texas United States 78229
    17 Hospital Miguel Hidalgo Aguascalientes Mexico 20230
    18 Instituto Mexicano de Trasplantes Cuernavaca Mexico 62448
    19 Hospital Central Dr. Ignacio Morones Prieto San Luis Potosi Mexico 78240

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01663740
    Other Study ID Numbers:
    • WV25651
    First Posted:
    Aug 13, 2012
    Last Update Posted:
    Aug 31, 2018
    Last Verified:
    Jul 1, 2018
    Additional relevant MeSH terms:
    Cytomegalovirus Infections
    Valganciclovir

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with donor positive (D+)/recipient negative (R-) cytomegalovirus (CMV) serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with donor negative (D-)/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Period Title: Overall Study
    STARTED 38 21
    COMPLETED 22 13
    NOT COMPLETED 16 8

    Baseline Characteristics

    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants Total
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant. Total of all reporting groups
    Overall Participants 37 21 58
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    35.6
    (7.96)
    32.5
    (5.81)
    34.5
    (7.36)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    37
    100%
    21
    100%
    58
    100%
    Seminal Volume (milliliters (mL)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milliliters (mL)]
    2.4
    (1.51)
    2.0
    (1.37)
    2.2
    (1.46)
    Sperm Density (millions of sperm/milliliter (mil/mL)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millions of sperm/milliliter (mil/mL)]
    21.0
    (28.33)
    23.2
    (24.90)
    21.9
    (26.77)
    Percentage of Normal Sperm Cells (percentage of normal sperm cells) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of normal sperm cells]
    11.4
    (18.44)
    33.5
    (39.03)
    20.3
    (30.15)
    Total Motility of Sperm (percent motility) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percent motility]
    25.8
    (20.46)
    36.3
    (24.24)
    30.0
    (22.42)
    Terminal Uridine Nick-End Labeling (TUNEL) Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    14.4
    (9.80)
    12.9
    (10.60)
    13.8
    (10.03)
    Follicle Stimulating Hormone (FSH) Level (units per liter (U/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units per liter (U/L)]
    10.8
    (6.77)
    8.6
    (6.61)
    9.9
    (6.72)
    Luteinizing Hormone (LH) Level (milliunits per milliliter (mU/mL)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milliunits per milliliter (mU/mL)]
    6.4
    (2.61)
    6.8
    (6.86)
    6.6
    (4.76)
    Prolactin Level (mU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mU/mL]
    175.4
    (73.51)
    164.5
    (46.22)
    170.9
    (63.46)
    Testosterone Level (nanomoles per liter (nmol/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [nanomoles per liter (nmol/L)]
    14.2
    (5.83)
    11.3
    (5.54)
    13.0
    (5.84)
    Inhibin B Level (picograms per milliliter (pg/mL)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [picograms per milliliter (pg/mL)]
    103.4
    (55.82)
    149.1
    (98.45)
    122.3
    (78.70)

    Outcome Measures

    1. Primary Outcome
    Title Change in Sperm Density From Baseline to the End of Treatment (EOT)
    Description Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (EOT) minus (-) the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).
    Time Frame Baseline, EOT (Week 28)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 24 14
    Mean (Standard Error) [mil/mL]
    -9.770
    (9.0518)
    30.396
    (11.3044)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0075
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm density,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -40.166
    Confidence Interval (2-Sided) 95%
    -68.869 to -11.463
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 14.1387
    Estimation Comments Change in sperm density from Baseline to EOT
    2. Secondary Outcome
    Title Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU)
    Description Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at post-baseline visit (EOT and FU) minus the TUNEL score measured at baseline for each participant. A negative change from baseline indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0 percent (%) to 100%, higher score represents more fragmentation.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 22 14
    Change at EOT
    -3.595
    (1.7720)
    -5.354
    (2.0680)
    Change at end of FU
    -4.516
    (1.9542)
    -3.465
    (2.5475)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5109
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline TUNEL score,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 1.758
    Confidence Interval (2-Sided) 95%
    -3.619 to 7.135
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.6460
    Estimation Comments Change in TUNEL score from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7449
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline TUNEL score,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -1.051
    Confidence Interval (2-Sided) 95%
    -7.566 to 5.464
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.2058
    Estimation Comments Change in TUNEL score from Baseline to end of FU
    3. Secondary Outcome
    Title Change in TUNEL Score From EOT to End of FU
    Description Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at FU minus the TUNEL score measured at EOT for each participant. A negative change from EOT indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0% to 100%, higher score represents more fragmentation.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 16 9
    Mean (Standard Error) [percent score]
    4.447
    (2.0671)
    1.578
    (2.5315)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3940
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline TUNEL score,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 2.869
    Confidence Interval (2-Sided) 95%
    -4.001 to 9.739
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.2934
    Estimation Comments Change in TUNEL score from EOT to end of FU
    4. Secondary Outcome
    Title Change in Seminal Volume From Baseline to EOT and End of FU
    Description Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at post-baseline visit (EOT and FU) - the seminal volume measured at baseline for each participant. A negative change from baseline indicated a lower seminal volume (worsening).
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 25 14
    Change at EOT
    -0.193
    (0.2324)
    -0.347
    (0.2967)
    Change at end of FU
    -0.289
    (0.2066)
    -0.161
    (0.2685)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6773
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline semen volume,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 0.155
    Confidence Interval (2-Sided) 95%
    -0.594 to 0.903
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.3687
    Estimation Comments Change in seminal volume from Basline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7046
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline semen volume,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -0.128
    Confidence Interval (2-Sided) 95%
    -0.806 to 0.551
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.3343
    Estimation Comments Change in seminal volume from Baseline to end of FU
    5. Secondary Outcome
    Title Change in Seminal Volume From EOT to End FU
    Description Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at FU - the seminal volume measured at EOT for each participant. A negative change from EOT indicated a lower seminal volume (worsening).
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 20 9
    Mean (Standard Error) [mL]
    -0.103
    (0.2187)
    0.024
    (0.3067)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7323
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline semen volume,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -0.128
    Confidence Interval (2-Sided) 95%
    -0.888 to 0.633
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.3684
    Estimation Comments Change in seminal volume from EOT to end of FU
    6. Secondary Outcome
    Title Change in Sperm Density From EOT to End of FU
    Description Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at FU - the sperm density measured at EOT for each participant. A negative change from EOT indicated a lower sperm density (worsening).
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 19 9
    Mean (Standard Error) [mil/mL]
    57.149
    (17.7736)
    5.882
    (27.4837)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1756
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm density,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 51.267
    Confidence Interval (2-Sided) 95%
    -24.626 to 127.159
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 36.6869
    Estimation Comments Change in sperm density from EOT to end of FU
    7. Secondary Outcome
    Title Change in Sperm Density From Baseline to End of FU
    Description Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (FU) - the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).
    Time Frame Baseline, end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 20 10
    Mean (Standard Error) [mil/mL]
    39.671
    (11.6679)
    49.866
    (15.8282)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6058
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm density,age,& duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -10.195
    Confidence Interval (2-Sided) 95%
    -49.934 to 29.543
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 19.5745
    Estimation Comments Change in sperm density from Baseline to end of FU
    8. Secondary Outcome
    Title Change in Total Motility of Sperm From Baseline to EOT and End of FU
    Description Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at post-baseline visit (EOT and FU) - the sperm motility measured at baseline for each participant. A negative change from baseline indicated a lower sperm motility (worsening).
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 24 14
    Change at EOT
    3.839
    (5.4259)
    25.667
    (6.9723)
    Change at FU
    24.736
    (4.7920)
    34.538
    (6.6024)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0222
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm motility,age,duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -21.828
    Confidence Interval (2-Sided) 95%
    -40.346 to -3.311
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.1214
    Estimation Comments Change in total motility of sperm from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2495
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm motility,age,duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -9.802
    Confidence Interval (2-Sided) 95%
    -26.795 to 7.190
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.3702
    Estimation Comments Change in total motility of sperm from Baseline to end of FU
    9. Secondary Outcome
    Title Change in Total Motility of Sperm From EOT to End of FU
    Description Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at FU - the sperm motility measured at EOT for each participant. A negative change from EOT indicated a lower sperm motility (worsening).
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 19 9
    Mean (Standard Error) [percent motility]
    8.953
    (6.3968)
    20.635
    (9.0663)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3505
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm motility,age,duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -11.683
    Confidence Interval (2-Sided) 95%
    -37.039 to 13.674
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 12.2576
    Estimation Comments Change in total motility of sperm from EOT to end of FU
    10. Secondary Outcome
    Title Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU
    Description Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at post-baseline visit (EOT and FU) - the sperm morphology measured at baseline for each participant. A positive change from baseline indicated an improved sperm morphology.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 21 12
    Change at EOT
    3.720
    (4.0233)
    9.461
    (5.2737)
    Change at end of FU
    5.128
    (2.8907)
    6.982
    (4.2060)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4021
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm morphology,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -5.741
    Confidence Interval (2-Sided) 95%
    -19.524 to 8.042
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.7578
    Estimation Comments Change in sperm morphology from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7229
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm morphology,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -1.854
    Confidence Interval (2-Sided) 95%
    -12.423 to 8.714
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.1817
    Estimation Comments Change in sperm morphology from Baseline to end of FU
    11. Secondary Outcome
    Title Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From EOT to End of FU
    Description Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at FU - the sperm morphology measured at EOT for each participant. A positive change from EOT indicated an improved sperm morphology.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 17 7
    Mean (Standard Error) [percentage of normal sperm cells]
    -0.714
    (4.3420)
    2.236
    (5.8507)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7080
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline sperm morphology,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -2.950
    Confidence Interval (2-Sided) 95%
    -19.192 to 13.291
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.7598
    Estimation Comments Change in sperm morphology from EOT to end of FU
    12. Secondary Outcome
    Title Change in Total Testosterone Level From Baseline to EOT and End of FU
    Description Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at post-baseline visit (EOT and FU) - the testosterone level measured at baseline for each participant. A negative change from baseline indicated a lower testosterone level.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 26 14
    Change at EOT
    0.762
    (1.0203)
    2.623
    (1.3586)
    Change at end of FU
    0.395
    (1.0260)
    1.509
    (1.3074)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2673
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline testosterone,age,duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -1.861
    Confidence Interval (2-Sided) 95%
    -5.213 to 1.491
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.6512
    Estimation Comments Change in total testosterone level from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4949
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline testosterone,age,duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -1.114
    Confidence Interval (2-Sided) 95%
    -4.392 to 2.164
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.6147
    Estimation Comments Change in total testosterone level from Baseline to end of FU
    13. Secondary Outcome
    Title Change in Total Testosterone Level From EOT to End of FU
    Description Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at FU - the testosterone level measured at EOT for each participant. A negative change from EOT indicated a lower testosterone level.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 19 11
    Mean (Standard Error) [nmol/L]
    -0.936
    (0.9950)
    -0.984
    (1.2012)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9753
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline testosterone,age,duration of pre-transplant dialysis as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 0.047
    Confidence Interval (2-Sided) 95%
    -3.063 to 3.157
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.5100
    Estimation Comments Change in total testosterone level from EOT to end of FU
    14. Secondary Outcome
    Title Change in LH Level From Baseline to EOT and End of FU
    Description LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at post-baseline visit (EOT and FU) - the LH level measured at baseline for each participant. A negative change from baseline indicated a lower LH level.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 26 13
    Change at EOT
    -0.281
    (0.3743)
    -0.357
    (0.5190)
    Change at end of FU
    -1.857
    (0.2787)
    -0.642
    (0.3635)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9053
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline LH concentration,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 0.076
    Confidence Interval (2-Sided) 95%
    -1.214 to 1.366
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.6347
    Estimation Comments Change in LH level from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0104
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline LH concentration,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -1.215
    Confidence Interval (2-Sided) 95%
    -2.125 to -0.305
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.4477
    Estimation Comments Change in LH level from Baseline to end of FU
    15. Secondary Outcome
    Title Change in LH Level From EOT to End of FU
    Description LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at FU - the LH level measured at EOT for each participant. A negative change from EOT indicated a lower LH level.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 20 11
    Mean (Standard Error) [mU/mL]
    -1.482
    (0.2607)
    -0.417
    (0.3207)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0143
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline LH concentration,age,& pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -1.065
    Confidence Interval (2-Sided) 95%
    -1.899 to -0.231
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.4057
    Estimation Comments Change in LH level from EOT to end of FU
    16. Secondary Outcome
    Title Change in FSH Level From Baseline to EOT and End of FU
    Description FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at post-baseline visit (EOT and FU) - the FSH level measured at baseline for each participant. A negative change from baseline indicated a lower FSH level.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 26 13
    Change at EOT
    1.521
    (1.0033)
    -1.020
    (1.4072)
    Change at end of FU
    -2.905
    (0.4113)
    -1.922
    (0.5369)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1505
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline FSH concentration,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 2.541
    Confidence Interval (2-Sided) 95%
    -0.969 to 6.052
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.7274
    Estimation Comments Change in FSH level from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1539
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline FSH concentration,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -0.983
    Confidence Interval (2-Sided) 95%
    -2.352 to 0.387
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.6739
    Estimation Comments Change in FSH level from Baseline to end of FU
    17. Secondary Outcome
    Title Change in FSH Level From EOT to End of FU
    Description FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at FU - the FSH level measured at EOT for each participant. A negative change from EOT indicated a lower FSH level.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 20 11
    Mean (Standard Error) [U/L]
    -3.462
    (0.5036)
    -1.988
    (0.6141)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0798
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline FSH concentration,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -1.474
    Confidence Interval (2-Sided) 95%
    -3.136 to 0.188
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.8084
    Estimation Comments Change in FSH level from EOT to end of FU
    18. Secondary Outcome
    Title Change in Prolactin Level From Baseline to EOT and End of FU
    Description Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at post-baseline visit (EOT and FU) - the prolactin level measured at baseline for each participant. A negative change from baseline indicated a lower prolactin level.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 25 13
    Change at EOT
    15.590
    (14.4761)
    15.693
    (19.2663)
    Change at end of FU
    9.829
    (13.1691)
    -5.443
    (16.7203)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9965
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline prolactin level,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -0.104
    Confidence Interval (2-Sided) 95%
    -47.792 to 47.585
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 23.4660
    Estimation Comments Change in prolactin level from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4636
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline prolactin level,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 15.272
    Confidence Interval (2-Sided) 95%
    -26.599 to 57.142
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 20.6031
    Estimation Comments Change in prolactin level from Baseline to end of FU
    19. Secondary Outcome
    Title Change in Prolactin Level From EOT to End of FU
    Description Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at FU - the prolactin level measured at EOT for each participant. A negative change from EOT indicated a lower prolactin level.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 19 11
    Mean (Standard Error) [mU/mL]
    -7.429
    (10.9988)
    -16.169
    (13.5322)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6134
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline prolactin level,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 8.740
    Confidence Interval (2-Sided) 95%
    -26.438 to 43.917
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 17.0805
    Estimation Comments Change in prolactin level from EOT to end of FU
    20. Secondary Outcome
    Title Change in Inhibin B Level From Baseline to EOT and End of FU
    Description Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at post-baseline visit (EOT and FU) - the inhibin B level measured at baseline for each participant. A negative change from baseline indicated a lower inhibin B level.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 22 12
    Change at EOT
    5.075
    (7.3778)
    -3.067
    (9.5924)
    Change at end of FU
    51.416
    (10.8658)
    10.734
    (13.9963)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5002
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline inhibin B level,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 8.142
    Confidence Interval (2-Sided) 95%
    -16.223 to 32.506
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 11.9301
    Estimation Comments Change in inhibin B level from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0279
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline inhibin B level,age,pre-transplant dialysis duration as explanatory variables.
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 40.682
    Confidence Interval (2-Sided) 95%
    4.720 to 76.643
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 17.6084
    Estimation Comments Change in inhibin B level from Baseline to end of FU
    21. Secondary Outcome
    Title Change in Inhibin B Level From EOT to End of FU
    Description Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at FU - the inhibin B level measured at EOT for each participant. A negative change from EOT indicated a lower inhibin B level.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 18 9
    Mean (Standard Error) [pg/mL]
    40.329
    (13.8221)
    14.448
    (17.8932)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2548
    Comments
    Method Mixed Models Analysis
    Comments Model adjusted for Cohort,visit,Cohort by visit interaction,baseline inhibin B level,age,pre-transplant dialysis duration as explanatory variables
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 25.881
    Confidence Interval (2-Sided) 95%
    -20.024 to 71.786
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 22.1348
    Estimation Comments Change in inhibin B level from EOT to end of FU
    22. Secondary Outcome
    Title Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU
    Description Abnormal sperm density was considered as sperm density less than (<) 20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from baseline to EOT and end of FU was reported.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 24 14
    Abnormal to abnormal: EOT
    50.0
    135.1%
    35.7
    170%
    Abnormal to abnormal: FU
    25.0
    67.6%
    20.0
    95.2%
    Normal to abnormal: EOT
    25.0
    67.6%
    7.1
    33.8%
    Normal to abnormal: FU
    0.0
    0%
    0.0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value 14.3
    Confidence Interval (2-Sided) 95%
    -19.3 to 45.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Change in abnormal to abnormal sperm density from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value 5.0
    Confidence Interval (2-Sided) 95%
    -34.3 to 43.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Change in abnormal to abnormal sperm density from Baseline to end of FU
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value 17.9
    Confidence Interval (2-Sided) 95%
    -15.3 to 48.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Change in normal to abnormal sperm density from Baseline to EOT
    23. Secondary Outcome
    Title Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU
    Description Abnormal sperm density was considered as sperm density <20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from EOT to end of FU was reported.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 19 9
    Abnormal to abnormal
    26.3
    71.1%
    22.2
    105.7%
    Normal to abnormal
    0.0
    0%
    0.0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value 4.1
    Confidence Interval (2-Sided) 95%
    -34.5 to 42.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Change in abnormal to abnormal sperm density from EOT to end of FU
    24. Secondary Outcome
    Title Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU
    Description Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 22 14
    EOT
    72.7
    196.5%
    71.4
    340%
    FU
    66.7
    180.3%
    60.0
    285.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    -31.3 to 33.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Improvement from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value 6.7
    Confidence Interval (2-Sided) 95%
    -31.1 to 44.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Improvement from Baseline to end of FU
    25. Secondary Outcome
    Title Percentage of Participants With Improved TUNEL Score From EOT to End of FU
    Description Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 16 9
    Number [percentage of participants]
    43.8
    118.4%
    55.6
    264.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value -11.8
    Confidence Interval (2-Sided) 95%
    -50.0 to 29.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Improvement from EOT to end of FU
    26. Secondary Outcome
    Title Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU
    Description Participants who had higher sperm density compared with the previous visit were considered as improved.
    Time Frame Baseline, EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 24 14
    EOT
    33.3
    90%
    64.3
    306.2%
    FU
    90.0
    243.2%
    80.0
    381%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value -31.0
    Confidence Interval (2-Sided) 95%
    -59.7 to 2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Improvement from Baseline to EOT
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value 10.0
    Confidence Interval (2-Sided) 95%
    -29.7 to 47.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Improvement from Baseline to end of FU
    27. Secondary Outcome
    Title Percentage of Participants With Improved Sperm Density From EOT to End of FU
    Description Participants who had higher sperm density compared with the previous visit were considered as improved.
    Time Frame EOT (Week 28), end of FU (Week 52)

    Outcome Measure Data

    Analysis Population Description
    Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    Measure Participants 19 9
    Number [percentage of participants]
    78.9
    213.2%
    88.9
    423.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort A: Partcipants Who Received Valganciclovir, Cohort B: Untreated Participants
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Percentage
    Estimated Value -9.9
    Confidence Interval (2-Sided) 95%
    -47.2 to 27.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Improvement from EOT to end of FU

    Adverse Events

    Time Frame Baseline up to end of study (Week 52)
    Adverse Event Reporting Description Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
    Arm/Group Title Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Arm/Group Description Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
    All Cause Mortality
    Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/31 (32.3%) 12/21 (57.1%)
    Gastrointestinal disorders
    Diarrhea 1/31 (3.2%) 0/21 (0%)
    Nausea 1/31 (3.2%) 0/21 (0%)
    Rectal hemorrhage 1/31 (3.2%) 0/21 (0%)
    Retroperitoneal hematoma 0/31 (0%) 1/21 (4.8%)
    General disorders
    Death 0/31 (0%) 1/21 (4.8%)
    Pyrexia 1/31 (3.2%) 0/21 (0%)
    Immune system disorders
    Transplant rejection 3/31 (9.7%) 1/21 (4.8%)
    Kidney transplant rejection 1/31 (3.2%) 1/21 (4.8%)
    Infections and infestations
    Urinary tract infection 1/31 (3.2%) 1/21 (4.8%)
    Atypical pneumonia 0/31 (0%) 1/21 (4.8%)
    Gastroenteritis 0/31 (0%) 1/21 (4.8%)
    Pyelonephritis 0/31 (0%) 1/21 (4.8%)
    Sinusitis 1/31 (3.2%) 0/21 (0%)
    Injury, poisoning and procedural complications
    Foreign body 0/31 (0%) 1/21 (4.8%)
    Perinephric collection 0/31 (0%) 1/21 (4.8%)
    Investigations
    Blood creatinine increased 0/31 (0%) 3/21 (14.3%)
    Pregnancy, puerperium and perinatal conditions
    Fetal death 0/31 (0%) 1/21 (4.8%)
    Renal and urinary disorders
    Acute kidney injury 3/31 (9.7%) 1/21 (4.8%)
    Hematuria 1/31 (3.2%) 0/21 (0%)
    Renal artery stenosis 0/31 (0%) 1/21 (4.8%)
    Tubulointerstitial nephritis 1/31 (3.2%) 0/21 (0%)
    Skin and subcutaneous tissue disorders
    Diabetic foot 1/31 (3.2%) 0/21 (0%)
    Social circumstances
    Treatment noncompliance 1/31 (3.2%) 0/21 (0%)
    Vascular disorders
    Hypertension 0/31 (0%) 1/21 (4.8%)
    Other (Not Including Serious) Adverse Events
    Cohort A: Partcipants Who Received Valganciclovir Cohort B: Untreated Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/31 (77.4%) 19/21 (90.5%)
    Blood and lymphatic system disorders
    Anaemia 7/31 (22.6%) 5/21 (23.8%)
    Leukopenia 6/31 (19.4%) 4/21 (19%)
    Polycythaemia 2/31 (6.5%) 1/21 (4.8%)
    Cardiac disorders
    Tachycardia 2/31 (6.5%) 0/21 (0%)
    Gastrointestinal disorders
    Abdominal pain 5/31 (16.1%) 1/21 (4.8%)
    Diarrhoea 4/31 (12.9%) 2/21 (9.5%)
    Constipation 3/31 (9.7%) 2/21 (9.5%)
    Nausea 4/31 (12.9%) 1/21 (4.8%)
    Vomiting 2/31 (6.5%) 3/21 (14.3%)
    Dyspepsia 2/31 (6.5%) 0/21 (0%)
    Gastritis 0/31 (0%) 2/21 (9.5%)
    Mouth ulceration 2/31 (6.5%) 0/21 (0%)
    Odynophagia 0/31 (0%) 2/21 (9.5%)
    General disorders
    Pyrexia 3/31 (9.7%) 4/21 (19%)
    Oedema peripheral 5/31 (16.1%) 0/21 (0%)
    Fatigue 4/31 (12.9%) 0/21 (0%)
    Immune system disorders
    Transplant rejection 3/31 (9.7%) 0/21 (0%)
    Infections and infestations
    Upper respiratory tract infection 4/31 (12.9%) 1/21 (4.8%)
    Urinary tract infection 1/31 (3.2%) 3/21 (14.3%)
    Escherichia infection 0/31 (0%) 3/21 (14.3%)
    Staphylococcal infection 2/31 (6.5%) 0/21 (0%)
    Injury, poisoning and procedural complications
    Incision site pain 4/31 (12.9%) 12/21 (57.1%)
    Procedural pain 2/31 (6.5%) 2/21 (9.5%)
    Incision site haemorrhage 2/31 (6.5%) 0/21 (0%)
    Perinephric collection 2/31 (6.5%) 0/21 (0%)
    Toxicity to various agents 0/31 (0%) 2/21 (9.5%)
    Investigations
    Blood creatinine increased 6/31 (19.4%) 4/21 (19%)
    Transaminases increased 5/31 (16.1%) 2/21 (9.5%)
    Immunosuppressant drug level increased 0/31 (0%) 4/21 (19%)
    Blood pressure increased 3/31 (9.7%) 0/21 (0%)
    Metabolism and nutrition disorders
    Hyperkalaemia 8/31 (25.8%) 2/21 (9.5%)
    Hypomagnesaemia 7/31 (22.6%) 0/21 (0%)
    Hypophosphataemia 5/31 (16.1%) 1/21 (4.8%)
    Dyslipidaemia 3/31 (9.7%) 1/21 (4.8%)
    Hypercalcaemia 2/31 (6.5%) 0/21 (0%)
    Hypervolaemia 2/31 (6.5%) 0/21 (0%)
    Musculoskeletal and connective tissue disorders
    Groin pain 3/31 (9.7%) 1/21 (4.8%)
    Pain in extremity 2/31 (6.5%) 0/21 (0%)
    Nervous system disorders
    Tremor 7/31 (22.6%) 5/21 (23.8%)
    Headache 3/31 (9.7%) 4/21 (19%)
    Hypoaesthesia 2/31 (6.5%) 1/21 (4.8%)
    Paraesthesia 1/31 (3.2%) 2/21 (9.5%)
    Psychiatric disorders
    Insomnia 3/31 (9.7%) 2/21 (9.5%)
    Renal and urinary disorders
    Haematuria 4/31 (12.9%) 5/21 (23.8%)
    Dysuria 1/31 (3.2%) 4/21 (19%)
    Hydronephrosis 3/31 (9.7%) 0/21 (0%)
    Proteinuria 1/31 (3.2%) 2/21 (9.5%)
    Reproductive system and breast disorders
    Scrotal swelling 2/31 (6.5%) 0/21 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/31 (3.2%) 3/21 (14.3%)
    Dyspnoea 3/31 (9.7%) 0/21 (0%)
    Rhinorrhoea 1/31 (3.2%) 2/21 (9.5%)
    Skin and subcutaneous tissue disorders
    Acne 2/31 (6.5%) 3/21 (14.3%)
    Rash 1/31 (3.2%) 3/21 (14.3%)
    Pruritus 2/31 (6.5%) 1/21 (4.8%)
    Alopecia 2/31 (6.5%) 0/21 (0%)
    Surgical and medical procedures
    Wound drainage 0/31 (0%) 2/21 (9.5%)
    Vascular disorders
    Hypertension 3/31 (9.7%) 3/21 (14.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01663740
    Other Study ID Numbers:
    • WV25651
    First Posted:
    Aug 13, 2012
    Last Update Posted:
    Aug 31, 2018
    Last Verified:
    Jul 1, 2018