Immunosuppression in Solid Organ Transplant Clinical Trial
Official title:
Evaluation of Belatacept as First Line Immunosuppression in De Novo Liver Transplant Recipients
| Verified date | September 2012 |
| Source | Bristol-Myers Squibb |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this clinical research study is to evaluate the effects of belatacept, relative to tacrolimus, on the incidence of rejection, graft loss and death in subjects receiving a liver transplant
| Status | Terminated |
| Enrollment | 260 |
| Est. completion date | June 2011 |
| Est. primary completion date | March 2010 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 70 Years |
| Eligibility |
Inclusion Criteria: - First time recipient of deceased donor liver transplant - Age 18-70 - Hepatitis C virus (HCV) positive recipients - For Long-term extension study-Subjects who have completed one year of study treatment (through Week 52) Target Disease Exclusions: Donor Exclusions a) Living donors b) ABO-incompatible donor recipient pairs c) Donor age < 12 or > 65 years d) Non heart-beating donors e) Anticipated cold ischemia time > 14 hours f) Donor Disease i) Known Human immunodeficiency virus (HIV) infection ii) Hepatitis B virus (HBV) surface antigen-positive or polymerase chain reaction (PCR)-positive donor if HBV negative recipient iii) HCV antibody-positive or PCR positive donor if HCV negative recipient Recipient Exclusions g) Subjects with a history of hypercoagulable state h) Subjects with fulminant hepatic failure i) Subjects receiving a split or reduced liver j) Subjects who are Epstein-Barr virus (EBV) negative Medical History and Concurrent Diseases 1. Subjects who have received 2 or more consecutive weeks of dialysis 1 month prior to enrollment OR anticipated to have prolonged dialysis post-transplantation 2. Subjects with known intrinsic renal disease (e.g., a urine protein/ creatinine ratio > 150 mg/g or the presence of an abnormal number of red blood cells (RBCs) or granular casts in the urine) AND calculated GFR < 40 ml/min/1.73 m^2 body surface area (BSA) (abbreviated Modification of Diet in Renal Disease [MDRD]). Subjects must have a calculated GFR assessment within 1 month prior to enrollment. 3. Subjects with known HIV 4. Subjects with any prior or concurrent solid organ (e.g., heart, kidney, pancreas) or cell (e.g., islet, bone marrow) transplant or subjects deemed likely to have a second solid organ or cell transplant (e.g., islet, bone marrow) within the next 3 years. 5. Subjects with a history of cancer within the last 5 years Allergies and Adverse Drug Reactions a) Hypersensitivity to any medications that will be used in the protocol Prohibited Treatments and/or Therapies 1. Subjects receiving immunosuppressive agent(s) (e.g., methotrexate, abatacept, infliximab, etanercept, chemotherapy, etc.) within the past 6 months for other indications such as an autoimmune disease 2. Subjects who received maintenance corticosteroids at a dose of > 5 mg/day of prednisone (or equivalent) for at least 7 consecutive days within the prior year for an underlying chronic inflammatory or autoimmune disease 3. Subjects who have used any investigational drug within 30 days prior to the Day 1 visit 4. Subjects previously treated with belatacept |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Local Institution | Ciudad De Buenos Aires | Buenos Aires |
| Austria | Local Institution | Wien | |
| Brazil | Local Institution | Centro-Porto Alegre | Rio Grande Do Sul |
| Brazil | Local Institution | Curitiba | Parana |
| Brazil | Local Institution | Rio De Janeiro | |
| Canada | Local Institution | Edmonton | Alberta |
| Canada | Local Institution | Toronto | Ontario |
| France | Local Institution | Clichy Cedex | |
| France | Local Institution | Lyon | |
| France | Local Institution | Montpellier | |
| France | Local Institution | Paris | |
| France | Local Institution | Toulouse Cedex 9 | |
| France | Local Institution | Villejuif | |
| Germany | Local Institution | Berlin | |
| Germany | Local Institution | Hamburg | |
| Germany | Local Institution | Hannover | |
| Germany | Local Institution | Heidelberg | |
| Germany | Local Institution | Tuebingen | |
| Italy | Local Institution | Bergamo | |
| Italy | Local Institution | Padova | |
| Italy | Local Institution | Pisa | |
| Italy | Local Institution | Roma | |
| Spain | Local Institution | Barcelona | |
| United States | Emory University Hospital | Atlanta | Georgia |
| United States | Carolinas Medical Center | Charlotte | North Carolina |
| United States | Northwestern University Feinberg School Of Medicine | Chicago | Illinois |
| United States | Univ. Of Cin. Coll. Of Med. | Cincinnati | Ohio |
| United States | Baylor University Medical Center | Dallas | Texas |
| United States | Henry Ford Hospital | Detriot | Michigan |
| United States | Mayo Clinic Transplant Department | Jacksonville | Florida |
| United States | Usc University Hospital | Los Angeles | California |
| United States | Froedtert Memorial Lutheran Hospital | Milwaukee | Wisconsin |
| United States | University Of Minnesota | Minneapolis | Minnesota |
| United States | Tulane Center For Abdominal Transplant | New Orleans | Louisiana |
| United States | Nyu School Of Medicine | New York | New York |
| United States | Integris-Baptist Medical Ctr. | Oklahoma City | Oklahoma |
| United States | Hospital Of The University Of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Mayo Clinic Hospital | Phoenix | Arizona |
| United States | University Of California San Francisco Medical Center | San Francisco | California |
| United States | Washington University School Of Medicine | St. Louis | Missouri |
| United States | Lifelink Healthcare Institute | Tampa | Florida |
| United States | Westchester Medical Center | Valhalla | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Bristol-Myers Squibb |
United States, Argentina, Austria, Brazil, Canada, France, Germany, Italy, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplant | Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading schema. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% (confidence interval) CI within each group, normal approximation is used if N>=5, otherwise exact method is used. | At 6 months posttransplant | |
| Primary | Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data) | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. | Day 1 (randomization) to Week 104 + within 56 Days after the last infusion/dose, Deaths were monitored up to database lock (20-June-2011) | |
| Primary | Number of Participants Who Had AEs of Special Interest During the LTE | AE of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial). | Day 1 (randomization) through database lock (20-June-2011) | |
| Primary | Number of Participants With Marked Hematology Abnormalities During the LTE | Low platelet count: <50*10^9 c/µl; Low leukocytes: <2.0*10^3 c/µl; Low lymphocytes (absolute): <0.5*10^3 c/µl; Low neutrophils (absolute): <1.0*10^3 c/µl. | Every 4 weeks from Week 53 to Week 104. | |
| Primary | Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE | ULN= upper limit of normal; Normal ranges are provided by the Central Laboratory and may vary according to sex and age. High alanine aminotransferase (ALT): >5.0*ULN U/L; High aspartate aminotransferase (AST): >5.0*ULN U/L; High direct bilirubin: >3.0*ULN mg/dL; High g-glutamyl transferase (GGT): >5.0*ULN U/L; High total bilirubin: >3.0*ULN mg/dL; High creatinine: > 3.0*ULN mg/dL | Every 4 weeks from Week 53 to Week 104. | |
| Primary | Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE | Low Serum Potassium: <3.0 meq/L; High serum potassium:>6.0 mEq/L; Low serum magnesium:<0.8 mEq/L; Low serum sodium: <130 mEq/L; High serum sodium: >155 mEq/L; Low inorganic phosphorus: <2.0 mg/dL; High uric acid: >10 mg/dL | Every 4 weeks from Week 53 to Week 104. | |
| Secondary | Percentage of Participants Surviving With Functional Graft: 12-month Treatment Phase | For 95% CI within each group, normal approximation was used if N>=5. Otherwise exact method was used. | At 6 and 12 months | |
| Secondary | Percentage of Participants Surviving With Functional Graft by End of Study (Includes LTE Data) | For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. | Day 1 (randomization) through database lock (20-June-2011) | |
| Secondary | Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by 12 Months | Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% CI within each group, normal approximation is used if N>=5. Otherwise exact method is used. For 95% CI of difference, adjustment is made for randomization strata if N >= 5 in each treatment arm. | At 12 months posttransplant | |
| Secondary | Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by End of Study (Includes LTE Data) | Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a central histopathologist using Banff criteria. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. | Day 1 (randomization) through database lock (20-June-2011) | |
| Secondary | Number of Participants Having Acute Rejections: 12-month Treatment Phase | Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted. | 3 , 6, and 12 months | |
| Secondary | Number of Participants Having Acute Rejections During the LTE | Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted. | Day 1 (randomization) through database lock (20-June-2011) | |
| Secondary | Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months | Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. TRT= treatment | 3, 6 and 12 months posttransplant | |
| Secondary | Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE | Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. DBL=database lock, TRT=treatment | Day 1 (randomization) through database lock (20-June-2011) | |
| Secondary | Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months | Acute Rejections (AR) were clinically suspected and biopsy proven by central pathologist. The Banff grading is a classification of renal allograft pathology and AR. Grade I: AR requiring moderate (>25%) to severe mononuclear cell interstitial infiltrate and moderate tubulitis; Grade II: AR requiring severe tubulitis and/or intimal arteritis; Grade III: AR requiring transmural arteritis. Only the episode with highest Banff grade for each participant was counted. | 3, 6 and 12 months posttransplant | |
| Secondary | Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months | Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted. | 3, 6 and 12 months posttransplant | |
| Secondary | Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE | Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted. | Day 1 (randomization) through End of study (database lock of 20-June-2011) | |
| Secondary | Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months | The time from transplantation to the first AR episode in each treatment arm was summarized using Kaplan-Meier curves. Acute Rejections were clinically suspected and biopsy proven by central pathologist. | 3, 6, 9 and 12 months posttransplant | |
| Secondary | Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase | GFR was assessed using a true measure of glomerular filtration via iothalamate clearance test. The month 2 time point was selected as the "baseline" time point with respect to measured GFR due to logistical difficulty in obtaining measured GFR at the time of liver transplant and post-transplant renal function largely stabilizing by 2 months. All Measured GFR > 200 were truncated at 200. | Baseline (2 month), 12 months posttransplant | |
| Secondary | Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase | GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m^2) = 170*(Scr)^-0.999*(Age)^-0.176*(0.762 if female)*(1.180 if African American)*(BUN)^-0.170*(Alb)^+0.318. ). BL= baseline, mL= milliliters; min= minute; m^2= meters squared. | Baseline [BL] (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant | |
| Secondary | Mean Change From Baseline in Calculated GFR During the LTE | GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m^2) = 170*(Scr)^-0.999*(Age)^-0.176*(0.762 if female)*(1.180 if African American)*(BUN)^-0.170*(Alb)^+0.318. ). BL= baseline, mL= milliliters; min= minute; m^2= meters squared. | Baseline (pretransplant time point), 1, 2, 3, 6,12, 18, 24, 30, 36 months posttransplant | |
| Secondary | Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12 | Measurement of SCr is commonly used as an indicator of renal function. High creatinine blood level is an indicator of deficient filtering by the kidney. SCr was determined at baseline and various post-baseline time points. | Baseline (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant | |
| Secondary | Mean Change in Baseline Values of Cystatin C at 2 and 12 Months | Cystatin C is a protein encoded by the CST3 gene, which is mainly used as a biomarker of kidney function. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise. | Baseline (pretransplant), 2, and 12 months posttransplant | |
| Secondary | Belatacept Pharmacokinetic (PK) Parameter: Maximum Serum Concentration | Maximum Plasma Concentration (Cmax) is the maximum observed serum drug concentration. | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. | |
| Secondary | Belatacept Pharmacokinetic (PK) Parameter: Time to Achieve the Maximum Plasma Concentration | Maximum Plasma Concentration (Tmax) is the time taken to reach the maximum observed plasma concentration. | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. | |
| Secondary | Belatacept PK Parameter: Area Under the Serum Concentration-time Curve to the End of the Dosing Period (AUCtau) | Area under the plasma concentration-time curve for each dosing interval is determined using the linear trapezoidal rule. The AUC(TAU) of belatacept from the MI regimens and LI regimens were calculated over 2 and 4 weeks respectively. | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. | |
| Secondary | Belatacept PK Parameter: Minimum Plasma Concentration | Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration. | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. | |
| Secondary | Belatacept PK Parameter: Terminal Half-life | Terminal Half-life (T 1/2) is the time a drug takes for the concentration levels to fall to 50% of their value. | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. | |
| Secondary | Belatacept PK Parameter: Total Body Clearance | Total body clearance is the rate and extent at which the drug is eliminated from the body. The clearance of a drug is used to understand the processes involved in drug elimination, distribution and metabolism. CLT was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state. | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. | |
| Secondary | Belatacept PK Parameter: Volume of Distribution | Volume of distribution (Vss) is the volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration. . Vss was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state. | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. | |
| Secondary | Belatacept PK Parameter: Amount Excreted in Ascites Fluid Over Days 1 to 14 | Amount Excreted in Ascites (Ae,asc) was estimated from the ascites drug concentrations and volumes within a dosing interval. | Days 1 to 14 | |
| Secondary | Belatacept PK Parameter: Clearance From Ascites Fluid | Clearance from ascites fluid was determined by amount excreted in ascites fluid (Ae, asc)[0-T] / AUC[0-T], where 0-T is the same duration relative to a belatacept infusion. | Days 1 to 14 | |
| Secondary | Belatacept Trough Concentration Before Each Infusion During the LTE | Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration. | Samples were collected predose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105, 532, 728. | |
| Secondary | Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) by 12 Months | HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score >= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score >= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N>=5 in both arms, otherwise exact method was used. | 6 and 12 months posttransplant | |
| Secondary | Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) During the LTE | HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score >= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score >= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N>=5 in both arms, otherwise exact method was used. | 12 months posttransplant, end of study (database lock, 20-June-2011) | |
| Secondary | Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase | Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels > 2.4 * 10^6 U/mL and > 4.7 * 10^6 U/mL were descriptively summarized by treatment group. BL=baseline | Baseline (pretransplant), 6 and 12 months (mo) posttransplant | |
| Secondary | Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE | Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels > 2.4 x 10^6 U/mL and > 4.7 x 10^6 U/mL were descriptively summarized by treatment group. BL = baseline | BL (pretransplant), 12, 18, 24, 30 months (mo) posttransplant | |
| Secondary | Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase | Percentage of participants who develop dyslipidemia, defined as hypertriglyceridemia (triglycerides [TGs] = 500 mg/dL [5.65 mmol/L]), hypercholesterolemia (Low density lipoprotein [LDL] = 100 mg/dL [2.59 mmol/L]), or elevated non-high density lipoprotein (non- high density lipoprotein [HDL] = 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs = 200 mg/dL [2.26 mmol/L]). | 6 and 12 months posttransplant | |
| Secondary | Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase | Percentage of participants at any given time (at Month 6 and Month 12) who met the definition of dyslipidemia.Dyslipidemia is defined as hypertriglyceridemia (TGs = 500 mg/dL [5.65 mmol/L]), hypercholesterolemia (LDL = 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL = 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs = 200 mg/dL [2.26 mmol/L]). | 6 and 12 months posttransplant | |
| Secondary | Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase | Baseline (pretransplant), 1, 6, 12 months posttransplant | ||
| Secondary | Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase | Baseline (pretransplant), 1, 6, 12 months posttransplant | ||
| Secondary | Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase | Baseline (pretransplant), 1, 6, 12 months posttransplant | ||
| Secondary | Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase | Baseline (pretransplant), 1, 6, 12 months posttransplant | ||
| Secondary | Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase | Baseline (pretransplant), 1, 6, 12 months posttransplant | ||
| Secondary | Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase | Baseline (pretransplant), 1, 3, 6, 9, 12 months posttransplant | ||
| Secondary | Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase | Participants were considered to have hypertension if they had Diastolic Blood Pressure (SBP) = 80 mmHg. | BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant | |
| Secondary | Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase | BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant | ||
| Secondary | Percentage of Participants Who Developed Hypertension in 12-month Treatment Phase | Percentage of participants who develop hypertension after randomization and transplantation. Transient post-operative increases in BP were not to be counted as new onset hypertension. Hypertension was to be assessed only at or after the Week 4 visit. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP = 130 mm Hg or DBP = 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension. | 6 and 12 months posttransplant | |
| Secondary | Percentage of Participants Who Have Hypertension at Any Given Time During the 12-month Treatment Phase | Percentage of participants at any given time who meet the definition of hypertension. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP = 130 mm Hg or DBP = 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension. | 6 and 12 months posttransplant | |
| Secondary | Number of Participants Who Received Anti-hypertensive Therapy at Month 12 | 12 months posttransplant | ||
| Secondary | Percentage of Participants With New Onset Diabetes Mellitus (NODM): 12-month Treatment Phase | A participant who did not have diabetes prior to randomization was determined to have NODM if(i) the participant received an antidiabetic medication for a duration of at least 30 days or(ii) at least two fasting plasma glucose (FPG) tests indicate that FPG is>=126 mg/dL (7.0 mmol/L). For 95% CI within each group, normal approximation is used if N>=5. For 95% CI of difference, adjustment is made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. | 6 and 12 months posttransplant | |
| Secondary | Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase | The HbA1c test is important in diabetes as a long-term measure of control over blood glucose, where the glucose bound to hemoglobin during the past 3-4 months is measured. A baseline diabetes participant was one who had a medical history of diabetes or being under anti-diabetic medication at the time of the transplantation. BL = baseline, DM = Diabetes mellitus. | 6, 12 months (mth) posttransplant | |
| Secondary | Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event | Day 1 (randomization) to 12 m + 8 week follow-up or = 56 days after discontinuation of study medication | |
| Secondary | Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase | AE of of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial), serious infections | Day 1 (randomization) to 12 months or = 56 days after discontinuation of study medication | |
| Secondary | Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase | Low hemoglobin: <8 g/dL; Low platelet count: <50*10^9 C/L; Low leukocytes: <2.0 *10^3 c/µL; Low lymphocytes (absolute): <0.5*10^3 c/µL; Low neutrophils (absolute): <1.0*10^3 Cc/µL. | Baseline (pretransplant), 2, 4, 8, 12 weeks, and every 4 weeks for week 16 to 52 | |
| Secondary | Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase | ULN= upper limit of normal; Normal ranges are provided by the central laboratory and may vary according to sex and age. High alkaline phosphatase (ALP): >5.0*ULN U/L; High alanine aminotransferase (ALT): >5.0*ULN U/L; High aspartate aminotransferase (AST): >5.0*ULN U/L; High direct bilirubin: >3.0 * ULN mg/dL; High g-glutamyl transferase (GGT): >5.0*ULN U/L; High total bilirubin: >3.0*ULN mg/dL; High creatinine: > 3.0*ULN mg/dL | Baseline (pretransplant), 4, 12, 24, 52 weeks | |
| Secondary | Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase | Low total calcium: <7 mg/dL; High total calcium: >12.5 mg/dL ; Low bicarbonate: <11 mEq/L; Low serum potassium: <3.0 mEq/L; High serum potassium:>6.0 mEq/L; High serum magnesium: >2.46 mEq/L; Low serum magnesium:<0.8 mEq/L; Low serum sodium: <130 mEq/L; High serum sodium: >155 mEq/L; Low inorganic phosphorus: <2.0 mg/dL; Low albumin: <2 g/dL; High uric acid: >10 mg/dL | Baseline (pretransplant), Weeks 4, 12, 24, and 52 | |
| Secondary | Number of Participants Who Had Abnormalities in Electrocardiograms: 12-month Treatment Phase | Baseline (pretransplant), Week 52 | ||
| Secondary | Change in Protein to Creatinine Ratio From Month 3 to Month 12. | Month 3 and 12 |