A Study to Determine the Excretion Balance, Pharmacokinetics, Metabolism and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Participants With Solid Tumors (Malignancies)

Hoffmann-La Roche8 enrolled

Overview

The purpose of this single-center, open-label, non-randomized study is to assess the excretion balance, pharmacokinetics, metabolism and absolute oral bioavailability of \[14C\]-labeled idasanutlin administered orally and \[13C\]-labeled idasanutlin administered intravenously in a single cohort of eligible participants. Participants will be screened for participation in this study within 21 days of receiving the first dose of study drug on Day 1. Treatment period will continue up to Day 28 after which participants will enter 28 day follow-up or the optional treatment extension of idasanutlin, depending on safety parameters and as per opinion of the Investigator.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, at the discretion of the Investigator * Histologically or cytologically confirmed advanced malignancy, except leukemia and lymphoma * Measureable or evaluable disease by Response evaluation criteria in solid tumors (RECIST) version 1.1, with no more than a single active malignancy in the previous 3 to 5 years prior to the administration of study drug * Life expectancy of at least 12 weeks * Participants taking opioid analgesics for pain should be on a stable pain and palliative care bowel regimen for one month prior to the first dose of study medication * Adequate bone marrow, hepatic, and renal function * Agreement to remain abstinent or use contraceptive methods specified in the study Exclusion Criteria: * History of any form of leukemia, except for Stage 0 - 1 chronic lymphocytic leukemia, not requiring treatment in addition to their underlying malignancy * Have received hormonal therapy within the two weeks prior to the first dose of study drug * Have pre-existing gastrointestinal disorders that may interfere with proper absorption of the drug * History of seizure disorders or unstable Central Nervous System metastases (participants with stable CNS metastases allowed) * Have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study * Receive certain per protocol prohibited medications while on study. These medications must be discontinued 7 days prior to start of study drug * Have bone marrow disorders, electrolyte imbalance, infrequent bowel movements (less than once per 48 hours), coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia * Positive for human immunodeficiency virus currently receiving combination anti-retroviral therapy * Regular work with ionizing radiation or radioactive material or treated with radiotherapy within 3 weeks prior to the first dose of study drug * Refuse to potentially receive blood products and/or have a hypersensitivity to blood products

Outcomes

Primary Outcomes

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Unlabeled Idasanutlin

Time frame: 0 Hour (hr) predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Maximum Observed Plasma Concentration (Cmax) of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Area Under the Plasma Concentration Time-Curve From Time Zero to Extrapolated Infinite Time (AUC [0-inf]) of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUC[0-last]) of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Plasma Elimination Half-Life (t1/2) of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Plasma Apparent Elimination Rate Constant of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Apparent Oral Clearance (CL/F) of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Renal Clearance (CLr) of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Apparent Volume of Distribution (Vz/F) of Unlabeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Cumulative Amount Excreted in Urine of Unlabeled Idasanutlin

Time frame: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose

Cumulative Amount Excreted in Feces of Unlabeled Idasanutlin

Tmax of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Cmax of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

AUC (0-inf) of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

AUC(0-last) of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Plasma t1/2 of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Plasma Apparent Elimination Rate Constant of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

CL/F of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

CLr of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Vz/F of Idasanutlin Metabolite

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Cumulative Amount Excreted in Urine of Idasanutlin Metabolite

Cumulative Amount Excreted in Feces of Idasanutlin Metabolite

Tmax of [13C]-Labeled Idasanutlin

Time frame: 0 hr predose, 5hr 55 minutes (min), 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

Cmax of [13C]-Labeled Idasanutlin

Time frame: 0 hr predose, 5hr 55 min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

AUC(0-inf) of [13C]-Labeled Idasanutlin

Time frame: 0 hr predose, 5hr 55 min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

AUC(0-last) of [13C]-Labeled Idasanutlin

Time frame: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

Plasma t1/2 of [13C]-Labeled Idasanutlin

Time frame: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

Absolute Oral Bioavailability of [13C]-Labeled Idasanutlin

Time frame: Oral administration: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose; IV administration: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

Whole Blood and Plasma Cmax of [14C]-Labeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Whole Blood and Plasma AUC(0-inf) of [14C]-Labeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Whole Blood and Plasma AUC(0-last) of [14C]-Labeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Whole Blood and Plasma Apparent Elimination Rate Constant of [14C]-Labeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Cumulative Amount of Radioactivity Excreted in Urine as Percentage of Dosed Radioactivity of [14C]-Labeled Idasanutlin

Cumulative Amount of Radioactivity Excreted in Feces as Percentage of Dosed Radioactivity of [14C]-Labeled Idasanutlin

CL/F of [13C]-Labeled Idasanutlin

Time frame: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

Vz/F of [13C]-Labeled Idasanutlin

Time frame: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose

Whole Blood and Plasma Tmax of [14C]-Labeled Idasanutlin

Time frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose

Cumulative Amount of Radioactivity Excreted in Feces on Toilet Tissue as Percentage of Dosed Radioactivity of [14C]-Labeled Idasanutlin

Secondary Outcomes

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Baseline through 28 days after the last dose of study drug (maximum up to approximately 76 days)

Palatability Assessment Questionnaire Score for Aqueous Dispersion of Idasanutlin

Time frame: 0 hr (pre-Day 11-dose), 0.5 hr, 1 hr, 1.5 hr, 2 hr, and 3 hr post-Day 11-dose

Aftertaste Survey Questionnaire Score for Aqueous Dispersion of Idasanutlin

Time frame: 0 hr (pre-Day 11-dose), 0.5 hr, 1 hr, 1.5 hr, 2 hr, and 3 hr post-Day 11-dose

A Study to Determine the Excretion Balance, Pharmacokinetics, Metabolism and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Participants With Solid Tumors (Malignancies)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes