Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

25 août 2020 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

7

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: Baseline up to Cycle 5 Day 45
Baseline up to Cycle 5 Day 45
Number of Participants With TEAEs Related to Vital Signs
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

19 mars 2014

Achèvement primaire (Réel)

17 décembre 2014

Achèvement de l'étude (Réel)

9 février 2016

Dates d'inscription aux études

Première soumission

26 septembre 2013

Première soumission répondant aux critères de contrôle qualité

26 septembre 2013

Première publication (Estimation)

1 octobre 2013

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

26 août 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

25 août 2020

Dernière vérification

1 août 2020

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner