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Phase 3b Study to Evaluate Advagraf in Combination With Mycophenolate Mofetil and Basiliximab in Liver Transplantation (DIAMOND)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01011205
First received: November 10, 2009
Last updated: January 16, 2013
Last verified: January 2013
History of Changes
  Purpose

Comparison of 3 dosing regimens of Advagraf to determine if there is a dosing regimen which may have the potential to cause fewer kidney problems.


Condition Intervention Phase
Liver Transplantation
 Drug: Advagraf
Drug: Mycophenolate Mofetil
Drug: Basiliximab
Drug: Corticosteroids
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Three Arm, Randomized, Open Label Clinical Study to Compare Renal Function in Liver Transplant Recipients Receiving an Immunosuppressive Regimen of Advagraf (Immediately or Delayed Post-transplant) and MMF With or Without a Monoclonal Anti-IL2R Antibody (Basiliximab)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Glomerular filtration rate (GFR) at 24 Weeks after transplantation estimated using the MDRD4 formula [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of and time to first incidence of the composite event: graft loss (defined as re-transplantation or death) or biopsy confirmed acute rejection (BCAR) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • GFR at 24 Weeks after transplantation measured by Iothalamate clearance [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • GFR at 24 Weeks after transplantation estimated using a Cystatin C based formula [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Creatinine clearance at 24 Weeks after transplantation estimated using the Cockcroft and Gault formula [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of and time to first incidence of acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of and time to first incidence of corticosteroid-resistant acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Overall frequency of acute rejection episodes [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of and time to first incidence of biopsy confirmed acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of and time to first incidence of biopsy confirmed corticosteroid-resistant acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Overall frequency of biopsy confirmed acute rejection episodes [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Severity of biopsy confirmed acute rejection episodes [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 901
Study Start Date: October 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dosing Regimen 1
Advagraf + MMF + Corticosteroids (Bolus)
 Drug: Advagraf
Capsule
Other Names:
  • FK506E
  • MR4
  • tacrolimus modified release
Drug: Mycophenolate Mofetil
Solution for infusion
Other Name: MMF
Drug: Corticosteroids
IV bolus
Other Name: Methylprednisolone or equivalent
Experimental: Dosing Regimen 2
Advagraf + MMF + Basiliximab + Corticosteroids (Bolus)
 Drug: Advagraf
Capsule
Other Names:
  • FK506E
  • MR4
  • tacrolimus modified release
Drug: Mycophenolate Mofetil
Solution for infusion
Other Name: MMF
Drug: Basiliximab
IV infusion
Other Name: Simulect
Drug: Corticosteroids
IV bolus
Other Name: Methylprednisolone or equivalent
Experimental: Dosing Regimen 3
Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus)
 Drug: Advagraf
Capsule
Other Names:
  • FK506E
  • MR4
  • tacrolimus modified release
Drug: Mycophenolate Mofetil
Solution for infusion
Other Name: MMF
Drug: Basiliximab
IV infusion
Other Name: Simulect
Drug: Corticosteroids
IV bolus
Other Name: Methylprednisolone or equivalent

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Undergoing orthotopic liver or split liver allograft transplantation
  • Female subject of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain effective birth control during the study

Exclusion Criteria:

  • Receiving a multi-organ transplant or having previous received an organ transplant (including liver re-transplantation)
  • Receiving an auxiliary graft or in whom a bio-artificial liver (cell system) has been used
  • Receiving ABO incompatible graft or a graft from a non heart beating donor
  • Ongoing dosing with systemic corticosteroids
  • Subjects with systemic infection requiring treatment except viral hepatitis

  • Diagnosis of new-onset malignancy prior to transplantation, with the exception of basocellular or squamous cell carcinoma of the skin which had been treated successfully. However, subjects with primary liver carcinoma can be included if they meet the following criteria:

    • < 3 nodes
    • no node larger than 5 cm
    • no metastases
    • no vascular tumoral invasion
  • Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer
  • Subject or donor known to be HIV positive
  • Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, basiliximab or mycophenolate mofetil or any of the product excipients
  • Pregnant woman or breast-feeding mother
  • Currently participating in another clinical trial, and/or has taken an investigational drug within 28 days prior to enrollment
  • Unlikely to comply with the Visits scheduled in the protocol
  • Any unstable medical condition that could interfere with the study objectives in the opinion of the Investigator
  • Receiving prohibited concomitant therapy, or received prohibited concomitant therapy within 28 days prior to enrollment
  • Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the Investigator, may complicate communication with the Investigator
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01011205

  Show 72 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Chair: Use Central Contact Astellas Pharma Global Development - EU
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01011205     History of Changes
Other Study ID Numbers: PMR-EC-1106, 2008-002231-32
Study First Received: November 10, 2009
Last Updated: January 16, 2013
Health Authority: Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Belarus: Ministry of Health
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Germany: Ministry of Health
Spain: Ministry of Health
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Hungary: National Institute of Pharmacy
Italy: National Institute of Health
Mexico: Secretaria de Salud
Norway: Norwegian Medicines Agency
Poland: Ministry of Health
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Sweden: The National Board of Health and Welfare
Switzerland: Federal Office of Public Health

Keywords provided by Astellas Pharma Inc:
Advagraf
Liver
Transplant
Immunosuppression

Additional relevant MeSH terms:
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Mycophenolate mofetil
Basiliximab
Antibodies, Monoclonal
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
 Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 16, 2013