A Study to Determine Pharmacokinetics of Children Receiving Modigraf (Tacrolimus Granules) Following Solid Organ Transplantation (OPTION)

A Multicentre, Open-label, Pharmacokinetic Study of Modigraf® (Tacrolimus Granules) in de Novo Paediatric Allograft Recipients

The purpose of this study is to find out how much of Modigraf is absorbed and used in the body and how fast it leaves the body (Pharmacokinetics). The results will then help to decide how much Modigraf in future can be given safely to children and young people following transplantation.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Kidney Transplantation; Heart Transplantation
• Intervention / Treatment: Drug: Tacrolimus granules

Detailed Description

The primary objective of this study is to determine the pharmacokinetics (PK) of tacrolimus following oral administration of Modigraf, after the first oral dose and at steady state in paediatric subjects undergoing de novo allograft transplantation.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Site 40
• France
  • Bron Cedex, France, 69677
    • Site: 60
• Germany
  • Hannover, Germany, 30625
    • Site 31
  • Heidelberg, Germany, 69120
    • Site 30
• Poland
  • Warsaw, Poland, 04-730
    • Site 50
• Spain
  • Madrid, Spain, 28007
    • Site 22
  • Madrid, Spain, 28046
    • Site 20
  • Madrid, Spain, 28046
    • Site 21
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Site 10
  • Manchester, United Kingdom, M13 9WL
    • Site 13

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The subject is the recipient of a solid organ (liver, kidney or heart) transplant. Multiorgan transplants are acceptable as long as one of the organs transplanted is liver, kidney or heart

Exclusion Criteria:

• The subject has previously received another organ transplant (including liver, kidney or heart re-transplantation)
• Subject has a high immunological risk, defined as a Panel Reactive Antibody (PRA) score >50% in the previous 6 months (only applicable for renal transplant recipients)
• Cold ischemia time of the donor kidney greater than 30 hours (only applicable for renal transplant recipients)
• Subject receives an AB0 incompatible donor organ
• Subject has significant renal impairment, defined as having serum creatinine ≥230 μmol/l (≥2.6 mg/dl) pre-transplantation (not applicable for renal transplant recipients)
• Subject has significant liver disease, defined as having elevated Alanine Aminotransferase (ALT) and/or Asparate Aminotransferase (AST) and/or Total Bilirubin levels 3 times the upper value of the normal range during the 28 days prior to transplantation (not applicable for liver transplant recipients)
• Subject with pulmonary vascular resistance greater than 4 Wood units which is unresponsive to treatment
• Subjects with malignancies or a history of malignancy within the last 5 years
• Subject has a significant, uncontrolled systemic infection and/or severe diarrhea, vomiting, active upper gastrointestinal disorder that may affect the absorption of tacrolimus or has an active peptic ulcer
• Subject requires systemic immunosuppressive medication for any indication other than transplantation
• Recipient or donor known to be HIV, HCV or HBV positive
• Known allergy or intolerance to steroids, macrolide antibiotics, basiliximab or tacrolimus
• Subject is currently participating in another clinical trial and/or has been taking an investigational drug in the 3 months prior to transplantation
• Subject is unlikely to comply with the visits scheduled in the protocol
• Subjects taking or requiring to be treated with medication or substances prohibited by this protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tacrolimus granules; oral	Drug: Tacrolimus granules; oral; Other Names: Modigraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine AUCtau (area under the plasma concentration-time curve for a dosing interval)	on Day 1 and Day 7 (+/- 7 days)
Determine Cmax (maximum concentration)	on Day 1 and Day 7 (+/- 7 days)
Determine tmax (time to attain Cmax)	on Day 1 and Day 7 (+/- 7 days)
Determine Ctrough (plasma concentration at the end of a dosing interval)	on Day 1 and Day 7 (+/- 7 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Rejection episodes	14 days
Patient survival	14 days
Graft survival	14 days
Assessment of safety through the evaluation of Adverse Events, laboratory parameters and vital signs	14 days

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe Ltd.
• Investigators: Study Chair: Senior Study Manager, Astellas Pharma Europe Ltd.

Publications and helpful links

General Publications

• Webb NJA, Baumann U, Camino M, Frauca E, Undre N; OPTION Study Group. Pharmacokinetics of tacrolimus granules in pediatric de novo liver, kidney, and heart transplantation: The OPTION study. Pediatr Transplant. 2019 Feb;23(1):e13328. doi: 10.1111/petr.13328. Epub 2019 Jan 21.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2011
• Primary Completion (Actual): February 3, 2015
• Study Completion (Actual): February 3, 2015

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimated): June 10, 2011

Study Record Updates

• Last Update Posted (Actual): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Heart Transplantation; Kidney Transplantation; Liver Transplantation
• Additional Relevant MeSH Terms: Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: F506-CL-0403; 2009-012258-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR