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Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

25 de agosto de 2020 atualizado por: Millennium Pharmaceuticals, Inc.

A Phase 1 Study of [ 14 C]-Ixazomib to Assess Mass Balance, Pharmacokinetics, and Metabolism in Patients With Advanced Solid Tumors or Lymphoma

This is a phase 1, 2-part, open-label study in 4 to 6 pharmacokinetic-evaluable participants with advanced solid tumors or lymphoma.

Visão geral do estudo

Status

Concluído

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

7

Estágio

  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

  • 18 years or older
  • Histologic or cytologic diagnosis of advanced or metastatic solid tumor or lymphoma for which no standard, curative, or life-prolonging therapies exist or are effective
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  • Female participants who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time during the entire study through 90 days after the last dose of study drug OR agree to practice true abstinence
  • Male participants who agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug OR agree to practice true abstinence
  • Voluntary written consent
  • Suitable venous access for the conduct of blood sampling
  • Recovered from the reversible effects of prior anticancer therapy

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Female participants who are lactating or breastfeeding or have a positive serum pregnancy test
  • Serious medical or psychiatric illness that could interfere with the study
  • Treatment with any investigational products or radiotherapy within 21 days before the first dose of study drug
  • Peripheral neuropathy greater than (>) Grade 2
  • Systemic treatment with strong and moderate inhibitors of CYP1A2, strong and moderate inhibitors of CYP3A, or clinically significant CYP3A inducers or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study drug
  • Symptomatic brain metastasis. Participants with brain metastases: must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks after completion of the definitive therapy; and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
  • Ongoing treatment with corticosteroids
  • Major surgery within the 14 days preceding the first dose of study drug
  • Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug
  • Life-threatening illness unrelated to cancer
  • Known hepatitis B surface antigen -positive, or known or suspected active hepatitis C infection or human immunodeficiency virus (HIV) positive
  • Diagnosed or treated for another malignancy within 2 years before the first dose, OR previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Any cardiovascular condition specified in the study protocol
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of IXAZOMIB
  • History of urinary and/or fecal incontinence
  • Inability to comply with study procedures or visit schedule including the requirement for inpatient confinement

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: IXAZOMIB

Part A: Participants will receive a single dose of 4.1-milligram (mg) [14C]-IXAZOMIB oral solution containing approximately 500-nCurie (nCi) of total radioactivity on Day 1 and remain at the clinic for 8 days. On Days 14 and 21, participants may be administered a single 4.0-mg capsule of IXAZOMIB. Participants will return to the clinic in the evening before Days 14, 21, 28, and 35 for a 24-hour overnight clinic visit.

Part B: Eligible participants from Part A may continue into Part B once they have completed their Day 35 assessments in Part A. Participants may receive IXAZOMIB capsules administered orally at a dose of 4.0-mg once weekly on Days 1, 8, and 15 of 28-day cycles. Participants will continue in this study until disease progression or unacceptable toxicity.

Part A: Ixazomib 4.1 mg containing approximately 500-nCi [14C]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21.

Part B: Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve.
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose
Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose
Time to reach the maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax of ixazomib after administration, obtained directly from the plasma concentration-time curve.
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose
Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to 312 hrs) post-dose
AUC(0-312) is a measure of the area under the plasma concentration time-curve from time zero to 312 hrs post-dose for ixazomib.
Day 1 of Part A pre-dose and at multiple timepoints (up to 312 hrs) post-dose
Part A: Cmax: Maximum Observed Plasma Concentration of TRA
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Maximum observed plasma concentration (Cmax) of TRA is the peak plasma concentration of TRA, obtained directly from the plasma TRA concentration-time curve.
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Part A: Tmax: Time to Reach the Cmax for TRA
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Time to reach the maximum observed plasma concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the plasma TRA concentration-time curve.
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose
AUC(0-816) is a measure of the area under the plasma concentration time-curve from time zero to 816 hrs post-dose for TRA.
Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose
Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Maximum observed whole blood concentration (Cmax) of a TRA is the peak whole blood concentration of TRA, obtained directly from the whole blood TRA concentration-time curve.
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Time to reach the maximum observed whole blood concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the whole blood TRA concentration-time curve.
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose
AUC(0-816) is a measure of the area under the whole blood concentration time-curve from time zero to 816 hrs post-dose for TRA.
Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose
Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine
Prazo: Day 1 of Part A from 0 to pre-dose and at multiple timepoints (up to 168 hrs) post-dose
Percentage of the ixazomib dose excreted unchanged in the urine from 0 to 168 hrs post-dose.
Day 1 of Part A from 0 to pre-dose and at multiple timepoints (up to 168 hrs) post-dose
Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Percentage of the TRA dose excreted in feces from Day 1 to Day 35 of Part A
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine
Prazo: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Percentage of the TRA dose excreted in urine from Day 1 to Day 35 of Part A.
Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
Part A: Renal Clearance of Ixazomib
Prazo: Day 1 pre-dose and at multiple timepoints (up to Day 14) post-dose
Renal clearance is the volume of plasma from which ixazomib is completely removed by the kidney in a given amount of time, calculated as the amount of ixazomib excreted in the urine divided by the area under the plasma ixazomib concentration-time curve.
Day 1 pre-dose and at multiple timepoints (up to Day 14) post-dose

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma
Prazo: Day 1 pre-dose and at multiple time points (up to 816 hrs) post-dose
The plasma samples were pooled for participants over 816 hrs post-dose, and data was analysed using the Hamilton method time-proportional pooling, and therefore the data is reported as "percent of total radioactivity in plasma" with measure type as "number" and measure dispersion as "Not applicable, NA".
Day 1 pre-dose and at multiple time points (up to 816 hrs) post-dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine
Prazo: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose
The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled urine. The data is therefore reported as "percentage of dose" with measure type as "number" and measure dispersion as "NA".
Day 1 pre-dose and at multiple time points (up to Day 35) post-dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces
Prazo: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose
The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled feces. The data is therefore reported as "percentage of dose" with measure type as "number" and measure dispersion as "NA".
Day 1 pre-dose and at multiple time points (up to Day 35) post-dose
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Prazo: Baseline up to Cycle 5 Day 45
Baseline up to Cycle 5 Day 45
Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values
Prazo: Baseline up to Cycle 5 Day 45
Baseline up to Cycle 5 Day 45
Number of Participants With TEAEs Related to Vital Signs
Prazo: Baseline up to Cycle 5 Day 25
Vital signs included oral body temperature, heart rate, and blood pressure.
Baseline up to Cycle 5 Day 25

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Publicações e links úteis

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Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

19 de março de 2014

Conclusão Primária (Real)

17 de dezembro de 2014

Conclusão do estudo (Real)

9 de fevereiro de 2016

Datas de inscrição no estudo

Enviado pela primeira vez

26 de setembro de 2013

Enviado pela primeira vez que atendeu aos critérios de CQ

26 de setembro de 2013

Primeira postagem (Estimativa)

1 de outubro de 2013

Atualizações de registro de estudo

Última Atualização Postada (Real)

26 de agosto de 2020

Última atualização enviada que atendeu aos critérios de controle de qualidade

25 de agosto de 2020

Última verificação

1 de agosto de 2020

Mais Informações

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Ensaios clínicos em IXAZOMIB

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