BK Virus (Nephropathy)
Conditions
Keywords
Vistide®, Cidofovir, renal transplant, BK Virus Nephropathy
Brief summary
This study will look at the safety, tolerability and effectiveness of cidofovir in kidney transplant patients who have been diagnosed with BK virus nephropathy (BKVN), a viral condition that can cause patients to reject transplanted kidneys. Up to 48 adult (age 18 years and older) kidney or pancreas transplant recipients with newly diagnosed BKVN will receive 1 of 3 cidofovir dose levels or placebo (non medicated substance) to identify the maximum tolerated dose. Dosing will be administered intravenously (by a tube running into a blood vessel). In addition to the screening visit, volunteers will actively participate for approximately 8-10 weeks with a single follow up phone call at 4 months. Blood samples, urine samples, eye exams and physical exams are included in study procedures.
Detailed description
The primary objectives of this randomized, double-blind, placebo-controlled, dose-escalation study are to evaluate the safety and tolerability of 3 dose levels of cidofovir when administered to renal transplant recipients with BK virus nephropathy and to identify the maximum tolerated doses (MTD) among the 3 dose levels of cidofovir in renal transplant recipients with BK virus nephropathy. The secondary study objectives are to evaluate the antiviral effect of cidofovir at each of 3 dose levels; to evaluate the pharmacokinetics (PK) of cidofovir in renal transplant recipients with underlying renal impairment; to evaluate the pharmacodynamics (PD) of cidofovir in this setting; to evaluate allograft function at the completion of the study; and to assess allograft rejection at the completion of the study. Patients with BKVN (virus nephropathy) diagnosed by positive plasma polymerase chain reaction (PCR) or renal allograft biopsy will be randomized to receive study drug within 60 days of the date of the renal biopsy or plasma PCR assay that established the diagnosis of BKVN. The study consists of three dose cohorts (0.25 mg/kg, 0.5 mg/kg and 1.0 mg/kg); each cohort will consist of approximately 12 subjects randomized 2:1 to receive either cidofovir or placebo (0.9% normal saline) to define the MTD among the three specified doses of cidofovir. Once the MTD is established, approximately 12 additional patients will be enrolled at that dose. The MTD is defined as the dose in which no more than 2 of the 8 cidofovir treated subjects experience a dose limiting toxicity (DLT). The target enrollment is 48 subjects if all dose cohorts are fully enrolled. A 25% over-enrollment may be tolerated to allow for continued enrollment of subjects in the lower dose cohort if data are under concomitant review by the Data and Safety Monitoring Board (DSMB) or to replace non-evaluable study participants. Study participants who have been randomized and have received cidofovir/placebo (in any cohort) will be considered non-evaluable if they discontinue from the study or die for any reason except toxicities definitely related to study treatment, including DLTs. These subjects may be replaced. There will be a 5-week drug administration period (4 doses) followed by a 2 week end-of-study observation and evaluation period for each cohort. At about 3 months after last dose of study infusion, a member of the research staff will assess the study participant and counsel on pregnancy status via a phone call. The study will be overseen by a DSMB who will review the data after each dose cohort is completed. The primary endpoint of the study will assess the safety and tolerability of cidofovir in kidney transplant recipients this will be assessed by enumeration of adverse events (AEs) reported by the subjects and/or investigator, and changes observed in the physical examination (including vital signs) and laboratory evaluations during the drug administration and end-of-treatment observation and evaluation periods. The severity and relationship of AEs to receipt of study drug will be determined because the primary endpoint is focusing on the safety. The secondary endpoints are the effect of cidofovir on BK virus as determined by: percentage of subjects who achieve an undetectable BK virus urine and plasma PCR between baseline and end of treatment; rate of reduction in urine and plasma BK virus load by quantitative PCR between baseline and end of treatment; and time to reduction in BK virus urine and plasma PCR; the detailed PK of cidofovir will be evaluated in subjects at the MTD; the PD of cidofovir will be assessed by quantitating the change in BK virus deoxyribonucleic aci
Interventions
DRUGCidofovir
Cidofovir is a marketed product for treatment of Cytomegalovirus disease (retinitis) in human immunodeficiency virus (HIV) infected patients. It is packaged as a sterile, hypertonic aqueous solution for intravenous infusion only. Dosages: 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg.
DRUGPlacebo
The control for this study is sterile, 0.9% normal saline for intravenous use.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged greater than or equal to 18 years. * Kidney or kidney/pancreas transplant recipient. * New onset BK Virus Nephropathy (BKVN) diagnosed by a positive plasma polymerase chain reaction (PCR) assay for BK virus deoxyribonucleic acid (DNA) or by a renal biopsy demonstrating BK virus (by immunohistochemistry, electron microscopy and/or in situ hybridization) obtained as part of standard medical care within 60 days prior to receipt of first dose of study drug. * BK virus load in plasma greater than 10,000 copies/mL within prior 21 days. * Glomerular filtration rate greater than 30 mL/min using Levey calculations. * Absolute neutrophil count greater than 1000/microliter \[with granulocyte colony stimulating factor (GCSF) support as necessary\]. * Women must be post-menopausal, surgically sterile or willing to use adequate contraception (barrier method with spermicide, intrauterine device, oral contraceptives, implant or other licensed hormone method) from time of study enrollment through 1 month after the last dose of study treatment. Men must be surgically sterile or willing to use contraception (barrier method with spermicide) from time of study enrollment through 3 months after the last dose of study treatment.
Exclusion criteria
* Unable to provide valid informed consent. * History of intolerance to cidofovir or related compounds (i.e. other nucleotide derivatives \[adefovir or tenofovir\]). * Pregnant or breast feeding women. * Prior treatment with cidofovir within the last 2 weeks. * Receipt of another investigational drug with proven nephrotoxic drug interaction with cidofovir or known antipolyoma virus activity one month prior to study entry. * Contraindication to renal biopsy (e.g., anticoagulant medication, unwilling to undergo biopsy). * Currently receiving or anticipated to receive any of the following within 2 weeks of randomization: * Amphotericin preparation (intravenous) * Aminoglycosides (intravenous) * Platinum - based chemotherapeutic agents * NSAIDs - non steroidal anti-inflammatory drugs (aspirin given for cardioprotective treatment is acceptable up to 650 mg per oral daily) * Foscarnet * Pentamidine (intravenous) * Probenecid * Leflunomide * Hypotony or uveitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Experiencing at Least One Laboratory Abnormality | Baseline through day 49 | The following lab values assessed during the 49 days of subject involvement were the following: hemoglobin, hematocrit, platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), serum creatinine, calcium, phosphorous, serum albumin, glucose, uric acid, magnesium, total protein, total bilirubin, alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphate. The outcome measure is the number of subjects experiencing at least 1 grade 1 (mild) or higher event. |
| Safety and Tolerability of Cidofovir Assessed by Enumeration of Adverse Events Per Subject | Baseline through day 49 | The measure is the number of adverse events (ie: events that are change from baseline)experienced by subjects. The median or average number of events and the range of events across all subjects is reported. |
| Number of Adverse Events by Grade of Event | Baseline through day 49. | Adverse events are reported as grades: Toxicity Grade I: a mild event (an event that requires minimal or no treatment and does not interfere with the subject's daily activities. Toxicity Grade II: a moderate event (an event that results in a low level of inconvenience or concern with the therapeutic measures and may cause some interference with functioning. Toxicity Grade III: a severe event (an event that interrupts a subject's usual daily activity and may require systemic drug therapy or other treatment and may be incapacitating. Toxicity Grade IV: Life threatening (any adverse drug experience that places the patient or subject at immediate risk of death from the reaction as it occurred) |
| Number of Related Adverse Events | Baseline through day 49. | The investigator's assessment of an AE's relationship to study drug is part of the documentation process. All adverse events had their relationship to study product assessed using the following terms: associated (related)or not associated (not related). To help assess, the following guidelines were used. * Associated - There was a known temporal relationship and/or, if re-challenge was done, the event abates with de-challenge and reappears with re-challenge and/or the event was known to occur in association study product or with a product in a similar class of study products * Not Associated -the AE was completely independent of study product administration; and/or evidence existed that the event was definitely related to another etiology. |
| Changes Observed in the Physical Examination : Respiratory Rate (Per Minute) | Baseline through day 49. | Respiratory rate is the number of breaths per minute. |
| Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Baseline through day 49. | Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels. Blood pressure usually refers to the arterial pressure of the systemic circulation. During each heartbeat, blood pressure varies between a maximum (systolic) and a minimum (diastolic) pressure. The measure is the difference between the baseline systolic and baseline diastolic value with the day 49 systolic and day 49 diastolic value. |
| Changes Observed in the Physical Examination: Body Temperature (Fahrenheit) | Baseline through day 49. | The temperature is a measure of body temperature in fahrenheit (F). The measure is a change between baseline temperature and day 49 temperature. |
| Changes Observed in the Physical Examination: Heart Rate (Per Minute) | Baseline through day 49. | The heart rate is the number of heart beats per minute. The outcome measure is the change from baseline heart rate to day 49 heart rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Day 35. | The outcome measure is the percent of subjects that achieved non-detectable BK virus in the urine and plasma polymerase chain reaction (PCR) at day 35 after staring study drug. Undetectable is a PCR viral load of less than 200. |
| Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Baseline, and each visit: day 7, 21, 35 and 49. | The percent change in viral load from baseline to day 7, day 21 and day 49 as measured in the urine and measured in the blood. A drop is identified by use of '-', an increase in viral load has no sign in front of the number. |
| Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Baseline through day 49. | — |
| Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Baseline through day 49. | — |
| Allograft Function at the Completion of the Study | Day 49. | Glomerular filtration rate (GFR) is a test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the tiny filters in the kidneys, called glomeruli, each minute. The normal health GFR is about 90 - 120 mL/min/1.73 m2. Older people will have lower normal GFR levels, because GFR decreases with age. Abnormal Results are expected to be below 60 mL/min/1.73 m2 for 3 or more months are a sign of chronic kidney disease. A GFR result below 15 mL/min/1.73 m2 may be a sign of kidney failure. |
| Allograft Rejection. | Day 49. | Allograft rejection is the number of subjects that rejected their kidney by the end of the study. |
| The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline Through Day 35 | Baseline through day 35 | PK parameter change from baseline to day 35 for Cmax. |
| The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline and Day 35 | Baseline through day 35 | PK parameter change from baseline to day 35 for AUC4 and AUC12 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort I - Cidofovir One dose (0.25 mg/kg/week-days 0, 7, 21, 35, 49) | 9 |
| Cohort I - Placebo One dose (0.25 mg/kg/week-days 0, 7, 21, 35, 49) | 5 |
| Cohort II - Cidofovir One dose (0.5 mg/kg/week-days 0, 7, 21, 35, 49) | 5 |
| Cohort II - Placebo One dose (0.5 mg/kg/week-days 0, 7, 21, 35, 49) | 3 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort I - Cidofovir | Cohort I - Placebo | Cohort II - Cidofovir | Cohort II - Placebo |
|---|---|---|---|---|---|
| Age, Customized 30-39 years old | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized < 30 years old | 3 participants | 1 participants | 2 participants | 0 participants | 0 participants |
| Age, Customized 40-49 years old | 4 participants | 1 participants | 2 participants | 0 participants | 1 participants |
| Age, Customized 50-59 years old | 6 participants | 3 participants | 1 participants | 2 participants | 0 participants |
| Age, Customized 60-69 years old | 7 participants | 4 participants | 0 participants | 2 participants | 1 participants |
| Age, Customized >= 70 years old | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 22 participants | 9 participants | 5 participants | 5 participants | 3 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 18 Participants | 6 Participants | 4 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 9 | 4 / 5 | 3 / 5 | 2 / 3 |
| serious Total, serious adverse events | 0 / 9 | 1 / 5 | 0 / 5 | 1 / 3 |
Outcome results
Primary
Changes Observed in the Physical Examination: Blood Pressure (mm/hg)
Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels. Blood pressure usually refers to the arterial pressure of the systemic circulation. During each heartbeat, blood pressure varies between a maximum (systolic) and a minimum (diastolic) pressure. The measure is the difference between the baseline systolic and baseline diastolic value with the day 49 systolic and day 49 diastolic value.
Time frame: Baseline through day 49.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I - Cidofovir | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Systolic Blood Pressure | 10 mm Hg |
| Cohort I - Cidofovir | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Diastolic Blood Pressure | 1 mm Hg |
| Cohort I - Placebo | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Diastolic Blood Pressure | 6 mm Hg |
| Cohort I - Placebo | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Systolic Blood Pressure | -4 mm Hg |
| Cohort II - Cidofovir | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Systolic Blood Pressure | -3 mm Hg |
| Cohort II - Cidofovir | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Diastolic Blood Pressure | 10 mm Hg |
| Cohort II - Placebo | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Systolic Blood Pressure | 3 mm Hg |
| Cohort II - Placebo | Changes Observed in the Physical Examination: Blood Pressure (mm/hg) | Diastolic Blood Pressure | -4 mm Hg |
Primary
Changes Observed in the Physical Examination: Body Temperature (Fahrenheit)
The temperature is a measure of body temperature in fahrenheit (F). The measure is a change between baseline temperature and day 49 temperature.
Time frame: Baseline through day 49.
Population: Subject's last visit minus baseline visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort I - Cidofovir | Changes Observed in the Physical Examination: Body Temperature (Fahrenheit) | 0.18 Temperature (F) |
| Cohort I - Placebo | Changes Observed in the Physical Examination: Body Temperature (Fahrenheit) | 0.72 Temperature (F) |
| Cohort II - Cidofovir | Changes Observed in the Physical Examination: Body Temperature (Fahrenheit) | -0.42 Temperature (F) |
| Cohort II - Placebo | Changes Observed in the Physical Examination: Body Temperature (Fahrenheit) | 0.3 Temperature (F) |
Primary
Changes Observed in the Physical Examination: Heart Rate (Per Minute)
The heart rate is the number of heart beats per minute. The outcome measure is the change from baseline heart rate to day 49 heart rate.
Time frame: Baseline through day 49.
Population: Subject's whose heart rate was measured at baseline and day 49 visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort I - Cidofovir | Changes Observed in the Physical Examination: Heart Rate (Per Minute) | -3 Change in Beats per Minute |
| Cohort I - Placebo | Changes Observed in the Physical Examination: Heart Rate (Per Minute) | 3 Change in Beats per Minute |
| Cohort II - Cidofovir | Changes Observed in the Physical Examination: Heart Rate (Per Minute) | 4 Change in Beats per Minute |
| Cohort II - Placebo | Changes Observed in the Physical Examination: Heart Rate (Per Minute) | -4 Change in Beats per Minute |
Primary
Changes Observed in the Physical Examination : Respiratory Rate (Per Minute)
Respiratory rate is the number of breaths per minute.
Time frame: Baseline through day 49.
Population: subjects whose respiratory rate was measured at baseline visit and at day 49 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort I - Cidofovir | Changes Observed in the Physical Examination : Respiratory Rate (Per Minute) | 0 Change in Breaths per Minute |
| Cohort I - Placebo | Changes Observed in the Physical Examination : Respiratory Rate (Per Minute) | 0 Change in Breaths per Minute |
| Cohort II - Cidofovir | Changes Observed in the Physical Examination : Respiratory Rate (Per Minute) | 0 Change in Breaths per Minute |
| Cohort II - Placebo | Changes Observed in the Physical Examination : Respiratory Rate (Per Minute) | -2 Change in Breaths per Minute |
Primary
Number of Adverse Events by Grade of Event
Adverse events are reported as grades: Toxicity Grade I: a mild event (an event that requires minimal or no treatment and does not interfere with the subject's daily activities. Toxicity Grade II: a moderate event (an event that results in a low level of inconvenience or concern with the therapeutic measures and may cause some interference with functioning. Toxicity Grade III: a severe event (an event that interrupts a subject's usual daily activity and may require systemic drug therapy or other treatment and may be incapacitating. Toxicity Grade IV: Life threatening (any adverse drug experience that places the patient or subject at immediate risk of death from the reaction as it occurred)
Time frame: Baseline through day 49.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - Cidofovir | Number of Adverse Events by Grade of Event | Grade 2 | 2 Events |
| Cohort I - Cidofovir | Number of Adverse Events by Grade of Event | Grade 1 | 26 Events |
| Cohort I - Cidofovir | Number of Adverse Events by Grade of Event | Grade 4 | 0 Events |
| Cohort I - Cidofovir | Number of Adverse Events by Grade of Event | Grad3 3 | 0 Events |
| Cohort I - Placebo | Number of Adverse Events by Grade of Event | Grade 1 | 4 Events |
| Cohort I - Placebo | Number of Adverse Events by Grade of Event | Grade 2 | 6 Events |
| Cohort I - Placebo | Number of Adverse Events by Grade of Event | Grad3 3 | 2 Events |
| Cohort I - Placebo | Number of Adverse Events by Grade of Event | Grade 4 | 0 Events |
| Cohort II - Cidofovir | Number of Adverse Events by Grade of Event | Grad3 3 | 0 Events |
| Cohort II - Cidofovir | Number of Adverse Events by Grade of Event | Grade 1 | 10 Events |
| Cohort II - Cidofovir | Number of Adverse Events by Grade of Event | Grade 4 | 0 Events |
| Cohort II - Cidofovir | Number of Adverse Events by Grade of Event | Grade 2 | 1 Events |
| Cohort II - Placebo | Number of Adverse Events by Grade of Event | Grad3 3 | 0 Events |
| Cohort II - Placebo | Number of Adverse Events by Grade of Event | Grade 1 | 2 Events |
| Cohort II - Placebo | Number of Adverse Events by Grade of Event | Grade 2 | 2 Events |
| Cohort II - Placebo | Number of Adverse Events by Grade of Event | Grade 4 | 0 Events |
Primary
Number of Related Adverse Events
The investigator's assessment of an AE's relationship to study drug is part of the documentation process. All adverse events had their relationship to study product assessed using the following terms: associated (related)or not associated (not related). To help assess, the following guidelines were used. * Associated - There was a known temporal relationship and/or, if re-challenge was done, the event abates with de-challenge and reappears with re-challenge and/or the event was known to occur in association study product or with a product in a similar class of study products * Not Associated -the AE was completely independent of study product administration; and/or evidence existed that the event was definitely related to another etiology.
Time frame: Baseline through day 49.
Population: Number of Related Events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I - Cidofovir | Number of Related Adverse Events | 6 Events |
| Cohort I - Placebo | Number of Related Adverse Events | 6 Events |
| Cohort II - Cidofovir | Number of Related Adverse Events | 1 Events |
| Cohort II - Placebo | Number of Related Adverse Events | 1 Events |
Primary
Number of Subjects Experiencing at Least One Laboratory Abnormality
The following lab values assessed during the 49 days of subject involvement were the following: hemoglobin, hematocrit, platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), serum creatinine, calcium, phosphorous, serum albumin, glucose, uric acid, magnesium, total protein, total bilirubin, alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphate. The outcome measure is the number of subjects experiencing at least 1 grade 1 (mild) or higher event.
Time frame: Baseline through day 49
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Phosphorous | 5 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Potassium | 1 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Protein | 4 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Glucose | 7 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Calcium | 5 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Creatinine | 8 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Bilirubin | 2 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Chloride | 4 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | BUN | 9 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Sodium | 3 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | ALT (SGPT) | 3 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hematocrit | 6 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Albumin | 4 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hemoglobin | 6 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | AST (SGOT) | 2 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Uric Acid | 1 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Bicarbonate | 5 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Platelets | 3 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Alkaline Phosphate | 4 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Magnesium | 5 Participants |
| Cohort I - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | WBC | 3 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Calcium | 0 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | WBC | 3 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hemoglobin | 5 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Chloride | 5 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Creatinine | 5 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Glucose | 2 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Uric Acid | 2 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Bicarbonate | 3 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Potassium | 1 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Magnesium | 2 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Protein | 3 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Phosphorous | 2 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Sodium | 2 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Bilirubin | 0 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | BUN | 5 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | ALT (SGPT) | 0 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Platelets | 2 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | AST (SGOT) | 3 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Albumin | 1 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Alkaline Phosphate | 0 Participants |
| Cohort I - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hematocrit | 5 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Creatinine | 4 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Uric Acid | 0 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Phosphorous | 1 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Calcium | 2 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Albumin | 1 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Glucose | 3 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Magnesium | 2 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Protein | 0 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Bilirubin | 0 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | ALT (SGPT) | 0 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | AST (SGOT) | 0 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Alkaline Phosphate | 2 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | WBC | 1 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | BUN | 4 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hemoglobin | 4 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hematocrit | 2 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Platelets | 3 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Sodium | 0 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Potassium | 1 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Chloride | 3 Participants |
| Cohort II - Cidofovir | Number of Subjects Experiencing at Least One Laboratory Abnormality | Bicarbonate | 2 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | WBC | 0 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Alkaline Phosphate | 0 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Phosphorous | 0 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hematocrit | 3 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | AST (SGOT) | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | ALT (SGPT) | 0 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Glucose | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Platelets | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Bilirubin | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Total Protein | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Calcium | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Sodium | 2 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Magnesium | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Uric Acid | 0 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Creatinine | 3 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | BUN | 2 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Bicarbonate | 2 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Chloride | 1 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Potassium | 0 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Serum Albumin | 2 Participants |
| Cohort II - Placebo | Number of Subjects Experiencing at Least One Laboratory Abnormality | Hemoglobin | 2 Participants |
Primary
Safety and Tolerability of Cidofovir Assessed by Enumeration of Adverse Events Per Subject
The measure is the number of adverse events (ie: events that are change from baseline)experienced by subjects. The median or average number of events and the range of events across all subjects is reported.
Time frame: Baseline through day 49
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort I - Cidofovir | Safety and Tolerability of Cidofovir Assessed by Enumeration of Adverse Events Per Subject | 3 Event |
| Cohort I - Placebo | Safety and Tolerability of Cidofovir Assessed by Enumeration of Adverse Events Per Subject | 4 Event |
| Cohort II - Cidofovir | Safety and Tolerability of Cidofovir Assessed by Enumeration of Adverse Events Per Subject | 3 Event |
| Cohort II - Placebo | Safety and Tolerability of Cidofovir Assessed by Enumeration of Adverse Events Per Subject | 7 Event |
Secondary
Allograft Function at the Completion of the Study
Glomerular filtration rate (GFR) is a test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the tiny filters in the kidneys, called glomeruli, each minute. The normal health GFR is about 90 - 120 mL/min/1.73 m2. Older people will have lower normal GFR levels, because GFR decreases with age. Abnormal Results are expected to be below 60 mL/min/1.73 m2 for 3 or more months are a sign of chronic kidney disease. A GFR result below 15 mL/min/1.73 m2 may be a sign of kidney failure.
Time frame: Day 49.
Population: subjects that had GFR at each visit last visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort I - Cidofovir | Allograft Function at the Completion of the Study | 42.7 mL/min/1.73 m2 |
| Cohort I - Placebo | Allograft Function at the Completion of the Study | 40.3 mL/min/1.73 m2 |
| Cohort II - Cidofovir | Allograft Function at the Completion of the Study | 45.1 mL/min/1.73 m2 |
| Cohort II - Placebo | Allograft Function at the Completion of the Study | 63.2 mL/min/1.73 m2 |
Secondary
Allograft Rejection.
Allograft rejection is the number of subjects that rejected their kidney by the end of the study.
Time frame: Day 49.
Population: Number of rejections
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I - Cidofovir | Allograft Rejection. | 0 Participants |
| Cohort I - Placebo | Allograft Rejection. | 0 Participants |
| Cohort II - Cidofovir | Allograft Rejection. | 0 Participants |
| Cohort II - Placebo | Allograft Rejection. | 0 Participants |
Secondary
Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine
Time frame: Baseline through day 49.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I - Cidofovir | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Urine | 14.5 Days |
| Cohort I - Cidofovir | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Plasma | 21.5 Days |
| Cohort I - Placebo | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Plasma | 7.5 Days |
| Cohort I - Placebo | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Urine | 35 Days |
| Cohort II - Cidofovir | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Urine | 29 Days |
| Cohort II - Cidofovir | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Plasma | 22 Days |
| Cohort II - Placebo | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Urine | 20 Days |
| Cohort II - Placebo | Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine | Plasma | 20.5 Days |
Secondary
Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit
The percent change in viral load from baseline to day 7, day 21 and day 49 as measured in the urine and measured in the blood. A drop is identified by use of '-', an increase in viral load has no sign in front of the number.
Time frame: Baseline, and each visit: day 7, 21, 35 and 49.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Plasma | 35.9 Percent Change |
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Urine | 27.6 Percent Change |
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Plasma | 21.6 Percent Change |
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Plasma | 56.5 Percent Change |
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Urine | 9.1 Percent Change |
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Urine | 42.4 Percent Change |
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Plasma | 44.8 Percent Change |
| Cohort I - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Urine | 18.3 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Plasma | 95.0 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Plasma | 61.9 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Urine | 19.1 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Plasma | 75.6 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Urine | 26.2 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Plasma | 91.3 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Urine | 29.9 Percent Change |
| Cohort I - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Urine | 86.1 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Plasma | 58.4 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Plasma | 76.7 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Urine | -3.1 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Plasma | 76.2 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Urine | -0.7 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Urine | 25.5 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Plasma | 21.2 Percent Change |
| Cohort II - Cidofovir | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Urine | 8.1 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Urine | 11.1 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 21 Plasma | 53.9 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Urine | 1.6 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Urine | 8.3 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Urine | 12.9 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 49 Plasma | 65.1 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 35 Plasma | 83.3 Percent Change |
| Cohort II - Placebo | Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit | Day 7 Plasma | 7.9 Percent Change |
Secondary
Subjects Achieving 50% Reduction Viral Load in Plasma and Urine
Time frame: Baseline through day 49.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - Cidofovir | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subjects at 50% Reduction in Plasma | 6 Participants |
| Cohort I - Cidofovir | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subject at 50% Reduction in Urine | 4 Participants |
| Cohort I - Placebo | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subject at 50% Reduction in Urine | 3 Participants |
| Cohort I - Placebo | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subjects at 50% Reduction in Plasma | 4 Participants |
| Cohort II - Cidofovir | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subjects at 50% Reduction in Plasma | 5 Participants |
| Cohort II - Cidofovir | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subject at 50% Reduction in Urine | 2 Participants |
| Cohort II - Placebo | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subjects at 50% Reduction in Plasma | 2 Participants |
| Cohort II - Placebo | Subjects Achieving 50% Reduction Viral Load in Plasma and Urine | Number of Subject at 50% Reduction in Urine | 1 Participants |
Secondary
The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR
The outcome measure is the percent of subjects that achieved non-detectable BK virus in the urine and plasma polymerase chain reaction (PCR) at day 35 after staring study drug. Undetectable is a PCR viral load of less than 200.
Time frame: Day 35.
Population: Percentage of subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - Cidofovir | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Urine | 0 percentage of subjects |
| Cohort I - Cidofovir | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Plasma | 0 percentage of subjects |
| Cohort I - Placebo | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Urine | 0 percentage of subjects |
| Cohort I - Placebo | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Plasma | 20 percentage of subjects |
| Cohort II - Cidofovir | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Plasma | 0 percentage of subjects |
| Cohort II - Cidofovir | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Urine | 0 percentage of subjects |
| Cohort II - Placebo | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Plasma | 0 percentage of subjects |
| Cohort II - Placebo | The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR | Urine | 0 percentage of subjects |
Secondary
The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline and Day 35
PK parameter change from baseline to day 35 for AUC4 and AUC12
Time frame: Baseline through day 35
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I - Cidofovir | The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline and Day 35 | AUC4 | 0.5 hr*mg/L |
| Cohort I - Cidofovir | The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline and Day 35 | AUC12 | 0.3 hr*mg/L |
| Cohort I - Placebo | The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline and Day 35 | AUC4 | -0.1 hr*mg/L |
| Cohort I - Placebo | The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline and Day 35 | AUC12 | 0.1 hr*mg/L |
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in plasma vs the PK AUC4 parameterp-value: 0.87Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in urine vs the PK AUC4 parameterp-value: 0.46Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in plasma vs the PK AUC4 parameterp-value: 0.49Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in urine vs the PK AUC4 parameterp-value: 0.05Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in plasma vs the PK AUC12 parameterp-value: 0.78Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in urine vs the PK AUC12 parameterp-value: 0.18Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in plasma vs the PK AUC12 parameterp-value: 0.75Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in urine vs the PK AUC12 parameterp-value: 0.75Spearman Correlation
Secondary
The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline Through Day 35
PK parameter change from baseline to day 35 for Cmax.
Time frame: Baseline through day 35
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort I - Cidofovir | The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline Through Day 35 | 190.4 ng/mL |
| Cohort I - Placebo | The Pharmacodynamics of Cidofovir Will be Assessed by Correlating the Percent Change in BK Virus DNA in Urine and Plasma With Pharmacokinetic Changes Between Baseline Through Day 35 | -233.9 ng/mL |
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in plasma vs the PK Cmax parameterp-value: 0.57Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in urine vs the PK Cmax parameterp-value: 0.53Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in plasma vs the PK Cmax parameterp-value: 0.62Spearman Correlation
Comparison: Spearman correlation co-efficient utilized to determine viral load changes in urine vs the PK Cmax parameterp-value: 0.1Spearman Correlation