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
  Purpose

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.


Condition Intervention Phase
Prophilaxis of Acute Rejection in Patients Receiving a Renal Allograft
Drug: 1
Drug: 2
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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)


Enrollment: 89
Study Start Date: May 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01056822

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

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01056822     History of Changes
Other Study ID Numbers: CERL080AES08, 2009-014562-26
Study First Received: January 25, 2010
Results First Received: April 10, 2014
Last Updated: December 2, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on August 02, 2015