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)

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.

Study Overview

• Status: Completed
• Conditions: Prophilaxis of Acute Rejection in Patients Receiving a Renal Allograft
• Intervention / Treatment: Drug: 1; Drug: 2

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Andalucia
    • Granada, Andalucia, Spain, 18014
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Castilla la Mancha
    • Toledo, Castilla la Mancha, Spain, 45004
      • Novartis Investigative Site
  • Castilla y Leon
    • Valladolid, Castilla y Leon, Spain, 47011
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08025
      • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08003
      • Novartis Investigative Site
    • Barcelona, Cataluña, Spain, 08036
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46017
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07014
      • Novartis Investigative Site
  • Las Palmas de Gran Canaria
    • La Laguna, Las Palmas de Gran Canaria, Spain, 38320
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31080
      • Novartis Investigative Site
  • Pais Vasco
    • Barakaldo, Pais Vasco, Spain, 48903
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Mycophenolate mofetil	Drug: 1; Continue with same dose of MMF as patient was taking before randomisation
Experimental: 2; Miycophenolate sodium	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Achieving at Least Two Mycophenolic Acid (MPA) Dose Steps Higher and Reducing Tacrolimus Dose at the End of the Study	at 12 months from baseline
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	at 12 months from baseline
Participants With Reduction in Tacrolimus or Tacrolimus Extended Release Levels at the End of the Study (Final Visit) Compared to Baseline Dose.	at 12 months from baseline
Mean Mycophenolic Acid (MPA) Doses at the End of the Study (Final Visit) Compared to Baseline Dose.	at 12 months from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)		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)
Glomerular Filtration Rate (GFR) Using Abbreviated MDRD	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	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)
Gastrointestinal Symptom Rating Scale (GSRS) Item Score	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)	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)
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score	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)	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)
Health-related Quality of Life (HRQoL): Impact of Gastrointestinal Symptoms on Quality Of Life (SIGIT)-QoL Questionnaire. Total Score.	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	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)
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	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)	at 12 months from baseline
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	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)	at 12 months from baseline
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	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)	at 12 months from baseline
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	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)	at 12 months from baseline
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	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)	at 12 months from baseline
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	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)	at 12 months from baseline
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	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	at 12 months from baseline
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	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	at 12 months from baseline
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	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	at 12 months from baseline
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	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	at 12 months from baseline
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	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	at 12 months from baseline
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	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	at 12 months from baseline
Duration of Exposure to the Study Medicinal Product, Mycophenolate Sodium Descriptive Statistics. Safety Population Per Treatment Group	Exposure to study drug (MPS). Data presented only for safety population on the study treatment arm (not applicable for MMF arm)	at 12 months from baseline
Dose of the Study Medicinal Product Mycophenolate Sodium (MPS)	Safety population per visit and per treatment group	at 12 months from baseline
Dose of the Study Medicinal Product Mycophenolate Mofetil (MMF)	Safety population per visit and per treatment group (missings not included)	at 12 months from baseline

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: January 25, 2010
• First Submitted That Met QC Criteria: January 25, 2010
• First Posted (Estimate): January 26, 2010

Study Record Updates

• Last Update Posted (Estimate): December 3, 2014
• Last Update Submitted That Met QC Criteria: December 2, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: CERL080AES08; 2009-014562-26