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Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate Sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate Mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study. (MAXIMIZA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01056822
First received: January 25, 2010
Last updated: December 2, 2014
Last verified: December 2014

January 25, 2010
December 2, 2014
May 2010
April 2013   (final data collection date for primary outcome measure)
  • Number of Participants Achieving at Least Two Mycophenolic Acid (MPA) Dose Steps Higher and Reducing Tacrolimus Dose at the End of the Study [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: No ]
  • Number of Participants That Achieved One Dose Step Higher With Mycophenolic Acid (MPA) or Mycophenolate Mofetil (MMF), According to the Treatment Group Assigned at the End of the Study (Final Visit) Compared to Baseline Dose [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: No ]
  • Participants With Reduction in Tacrolimus or Tacrolimus Extended Release Levels at the End of the Study (Final Visit) Compared to Baseline Dose. [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: No ]
  • Mean Mycophenolic Acid (MPA) Doses at the End of the Study (Final Visit) Compared to Baseline Dose. [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: No ]
to demonstrate that Myfortic® allows higher dose optimization than MMF measured as the percentage of patients who reach at least two dosage step greater than at baseline. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01056822 on ClinicalTrials.gov Archive Site
  • Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl) [ Time Frame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15) ] [ Designated as safety issue: No ]
  • Glomerular Filtration Rate (GFR) Using Abbreviated MDRD [ Time Frame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15) ] [ Designated as safety issue: No ]
    Calculated GFR (MDRD formula): GFR [mL/min/1.73m2] = 186.3*(C-1.154)*(A-0.203)*G*R where C is the serum concentration of creatinine [mg/dL], A is age [years], G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1
  • Gastrointestinal Symptom Rating Scale (GSRS) Item Score [ Time Frame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15) ] [ Designated as safety issue: Yes ]
    The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score [ Time Frame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15) ] [ Designated as safety issue: Yes ]
    The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Health-related Quality of Life (HRQoL): Impact of Gastrointestinal Symptoms on Quality Of Life (SIGIT)-QoL Questionnaire. Total Score. [ Time Frame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15) ] [ Designated as safety issue: Yes ]
    The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
  • Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
  • Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
  • Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
  • Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
  • Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
  • Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
  • Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
  • Duration of Exposure to the Study Medicinal Product, Mycophenolate Sodium Descriptive Statistics. Safety Population Per Treatment Group [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: No ]
    Exposure to study drug (MPS). Data presented only for safety population on the study treatment arm (not applicable for MMF arm)
  • Dose of the Study Medicinal Product Mycophenolate Sodium (MPS) [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Safety population per visit and per treatment group
  • Dose of the Study Medicinal Product Mycophenolate Mofetil (MMF) [ Time Frame: at 12 months from baseline ] [ Designated as safety issue: Yes ]
    Safety population per visit and per treatment group (missings not included)
  • To compare efficacy between the two groups of treatment by means of biopsy prove acute rejection (BPAR), graft loss, death and lost to follow up [ Time Frame: 1st month, 3rd month, 5th month, 7th month and 12th month ] [ Designated as safety issue: Yes ]
  • To compare the quality of life between both immunosuppressive regimens by SIGIT-QoL scale. [ Time Frame: 3th month, 7th month and 12th month ] [ Designated as safety issue: No ]
  • To compare the safety between both immunosuppressive regimens by adverse events report, vital signs and laboratory analysis results. [ Time Frame: 1st month, 3rd month, 5th month, 7th month and 12th month ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate Sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate Mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study.
Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate Sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate Mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study.
Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prophilaxis of Acute Rejection in Patients Receiving a Renal Allograft
  • Drug: 1
    Continue with same dose of MMF as patient was taking before randomisation
  • Drug: 2
    Increase MPS by 180mg every 12h based on investigator's judgement up to a maximum of 720 mg of MPS every 12 hours
  • Active Comparator: 1
    Mycophenolate mofetil
    Intervention: Drug: 1
  • Experimental: 2
    Miycophenolate sodium
    Intervention: Drug: 2
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
89
April 2013
April 2013   (final data collection date for primary outcome measure)

Inclusion criteria

  1. Renal transplant recipients ≥ 1 year and ≤ 5 years prior1 to inclusion in the study.
  2. Patients who were receiving an immunosuppressive regimen including MMF ≤1000 mg/day and ≥ 250 mg/day 4 and Prograf®1 or Advagraf®6 (levels ≥7 ng/ml).
  3. Patients who had been receiving the current maintenance immunosuppressive regimen with stable doses of MMF for at least the past 3 months.2
  4. Patients included must have had Prograf® or Advagraf® levels ≥ 7ng/ml4 for at least one month prior to inclusion in the trial.2
  5. Patients with low immunological risk, in the investigator's opinion.
  6. Patients with an estimated glomerular filtration rate based on the MDRD formula of > 30 ml/min x 1.73 m2.1
  7. Patients over 18 years of age.1
  8. Patients who were able to understand the study information and give written informed consent.
  9. Patients who were able to meet all study requirements, including completing questionnaires and attending study visits.

Exclusion criteria

  1. Patients with GI symptoms known or assumed not to be caused by mycophenolic acid (MPA) treatment (e.g. oral bisphosphonate-induced infectious diarrhoea).
  2. Patients with chronic inflammatory bowel disease.
  3. Diabetic patients.
  4. Acute rejection < 1 month prior to inclusion in the study.
  5. Patients with leukopenia (< 3500 cells/mm3) or thrombocytopenia (< 100,000 cells/mm3).
  6. Women of childbearing potential who were planning to become pregnant, were pregnant and/or breastfeeding, or who did not wish to use effective contraception [hormonal contraceptives (implantation, patches, oral) and double-barrier methods (any double combination of: IUD, male or female condoms with spermicidal gel, diaphragm, contraceptive sponge, cervical cap)].
  7. Presence of psychiatric illness (such as schizophrenia, major depression) that, in the investigator's opinion, could interfere with study requirements.
  8. Patients who were undergoing surgery for an acute condition or who were hospitalised.
  9. Any other medical condition that, in the investigator's opinion based on blood counts or chart review, could interfere with completion of the study, including but not limited to visual problems or cognitive impairment.
  10. Patients who were receiving or had received any investigational medicinal product during the 30 days prior to inclusion in the study.
Both
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01056822
CERL080AES08, 2009-014562-26
Yes
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP