- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01292226
A Study of the Correlation Between Pharmacokinetic and Pharmacodynamic Parameters of CellCept (Mycophenolate Mofetil).
8. april 2016 oppdatert av: Hoffmann-La Roche
Relationships Between Pharmacokinetic and Pharmacodynamic Strategies for Assessment of the Risks for Acute Rejection and Side Effects of Mycophenolate Mofetil
This study will evaluate the correlation between the pharmacokinetic and pharmacodynamic parameters of CellCept in patients undergoing primary kidney transplantation, in order to assess the impact on clinical outcome and the risks of acute rejection.
All patients will receive oral CellCept, 1g twice daily, and pharmacokinetic and pharmacodynamic parameters will be measured at weeks 2, 4, 12 and 24.
The anticipated time on study treatment is 24 weeks.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
45
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Bari, Italia, 70124
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Brescia, Italia, 25123
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Coppito, Italia, 67100
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Napoli, Italia, 80131
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Roma, Italia, 00168
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Torino, Italia, 10126
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Verona, Italia, 37126
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 65 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Adult patients, 18 to 65 years of age
- Patients undergoing primary kidney transplantation
Exclusion Criteria:
- Recipients of multiple organ transplants
- Prior therapy with CellCept
- Presence or history of malignancies, except for successfully treated basal or squamous cell carcinoma of the skin
- Active peptic ulcer or active serious digestive system disease that may affect the absorption of CellCept
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Mycophenolate Mofetil Monotherapy
Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks.
Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
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1 g PO BID for 24 weeks
Andre navn:
According to manufacturer recommendation
According to manufacturer recommendation
According to manufacturer recommendation
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Percentage of Participants With Acute Rejection
Tidsramme: Day 1, Weeks 2, 4, 12, 24, and 28
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Diagnosis of acute rejection was suspected in any participant with an increase in serum creatinine greater than or equal to (≥) 25 percent (%).
All suspected acute rejections were confirmed by biopsy.
The start date of acute rejection was identified as the date of biopsy.
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Day 1, Weeks 2, 4, 12, 24, and 28
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Time to Rejection
Tidsramme: Day 1, Weeks 2, 4, 12, 24, and 28
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The mean time, in days, from the date of enrollment to date of biopsy confirming acute rejection.
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Day 1, Weeks 2, 4, 12, 24, and 28
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Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR)
Tidsramme: Day 1, Weeks 2, 4, 12, 24, and 28
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BPAR was defined according to 1997 Banff Criteria as a biopsy Banff grade of IA, IB, IIA, IIB, or III.
Grade IA was defined as significant interstitial infiltration with greater than (>)25% of parenchyma affected, and foci of moderate tubulitis with >4 mononuclear cells per tubular cross section or group of 10 tubular cells.
Grade IB was defined as significant interstitial infiltration with >25% parenchyma affected, and foci of severe tubulitis with >10% mononuclear cells per tubular cross section or group of 10 tubular cells.
Grade IIA was defined as mild to moderate intimal arteritis.
Grade IIB was defined as severe intimal arteritis comprising >25% of the luminal area.
Grade III was defined as transmural arteritis and/or arterial fibrinoid changes and necrosis of medial smooth muscle cells.
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Day 1, Weeks 2, 4, 12, 24, and 28
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Percentage of Participants With Graft Loss
Tidsramme: Day 1, Weeks 2, 4, 12, 24, and 28
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An allograft was presumed to be lost if a participant started dialysis and was not able to subsequently be removed from dialysis.
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Day 1, Weeks 2, 4, 12, 24, and 28
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Percentage of Participants Surviving
Tidsramme: Day 1, Weeks 2, 4, 12, 24, and 28
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Day 1, Weeks 2, 4, 12, 24, and 28
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Total Mycophenolate Acid (MPA) by Visit and Timepoint
Tidsramme: Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up Visit), and any unscheduled visits
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Drug quantification of total MPA (micrograms per milliliter [mcg/mL]) in the plasma was measured at time (T) = 0 minutes (min), 40 mins, and 120 mins.
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Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up Visit), and any unscheduled visits
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Free MPA (mcg/mL) by Visit
Tidsramme: Weeks 2, 4, 12, 24, safety follow-up (Week 28), and any unscheduled visits
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Drug quantification of free MPA in the plasma was measured at T = 0, 40, and 120 mins.
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Weeks 2, 4, 12, 24, safety follow-up (Week 28), and any unscheduled visits
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MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit
Tidsramme: Predose and 40 minutes and 2 hours postdose at Weeks 2, 4, 12, and 24, and at the Safety follow-up (Week 28)
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The AUC0-12 of MPA was estimated on the validated limited sampling strategy, AUC (milligrams multiplied by height over liter [mg.h/L]) = 7.182 + 4.607 multiplied by (*) concentration at 0 minutes (C0)+ 0.998 * the concentration at 40 minutes (C0.67) + 2.149 * the concentration at 120 minutes (C2).
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Predose and 40 minutes and 2 hours postdose at Weeks 2, 4, 12, and 24, and at the Safety follow-up (Week 28)
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Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint
Tidsramme: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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IMPDH activity in peripheral blood mononuclear cells (PBMCs) was measured at 2 timepoints per visit, 0 and 120 minutes and presented in enzyme units.
The unit of measure of enzyme activity is "U".
One U is defined as the amount of the enzyme that produces a certain amount of enzymatic activity that is, the amount that catalyzes the conversion of 1 micro mole of substrate per minute under pre-specified conditions (temperature, pH).
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BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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IMPDH Expression I by Visit and Timepoint
Tidsramme: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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IMPDH I gene expression was measured by real time polymerase chain reaction (QRT-PCR) based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of messenger ribonucleic acid (mRNA) copies per cell (copies/cell).
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BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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IMPDH Expression II by Visit and Timepoint
Tidsramme: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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IMPDH II gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.
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BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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Interleukin 8 (IL-8) Expression by Visit and Timepoint
Tidsramme: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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IL-8 gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.
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BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint
Tidsramme: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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TNF gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.
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BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
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Percentage of Participants With Infection
Tidsramme: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
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Infections were graded according to the World Health Organization (WHO) worst grade observed.
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BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
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Percentage of Participants With Gastrointestinal Toxicities
Tidsramme: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-up Visit)
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Gastrointestinal adverse events (AEs) according to WHO worst grade observed.
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BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-up Visit)
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Percentage of Participants With Hematologic Toxicity
Tidsramme: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
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Hematological toxicities graded according to WHO worst grade observed (Grade 1=mild, Grade 2=moderate).
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BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
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Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH I Expression and Free Fraction
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH II Expression and Free Fraction
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Infection
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Hematologic Toxicity
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Gastrointestinal Toxicity
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity
Tidsramme: BL and Weeks 2, 4, 12, and 24
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The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
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BL and Weeks 2, 4, 12, and 24
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. desember 2006
Primær fullføring (Faktiske)
1. september 2008
Studiet fullført (Faktiske)
1. september 2008
Datoer for studieregistrering
Først innsendt
3. februar 2011
Først innsendt som oppfylte QC-kriteriene
8. februar 2011
Først lagt ut (Anslag)
9. februar 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
12. mai 2016
Siste oppdatering sendt inn som oppfylte QC-kriteriene
8. april 2016
Sist bekreftet
1. april 2016
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Enzymhemmere
- Antirevmatiske midler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Dermatologiske midler
- Antibakterielle midler
- Antibiotika, antineoplastisk
- Antifungale midler
- Antituberkulære midler
- Antibiotika, Antituberkulær
- Calcineurin-hemmere
- Antistoffer
- Mykofenolsyre
- Syklosporin
- Syklosporiner
Andre studie-ID-numre
- ML19835
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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