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)

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2018
• Main ID: NCT02828930
• Date of registration: 07/07/2016
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: 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)
• Scientific title: A Single-Center, Open-Label Study Investigating 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 Patients With Solid Tumors
• Date of first enrolment: September 8, 2016
• Target sample size: 8
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02828930
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Hungary

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Solid Tumors

Intervention(s)

Drug: [14C]-radiolabeled Idasanutlin

Drug: Placebo

Drug: Idasanutlin

Drug: [13C]-radiolabeled Idasanutlin

Primary Outcome(s)

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]

Cmax 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]

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]

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]

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

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]

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]

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]

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]

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]

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]

Cumulative Amount Excreted in Feces of Idasanutlin Metabolite [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]

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]

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]

AUC (0-inf) of Idasanutlin Metabolite [Time Frame: 0 hr predose, 1, 3, 6, 7, 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]

CL/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 [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]

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]

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]

CLr of Idasanutlin Metabolite [Time Frame: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose]

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

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]

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]

Renal Clearance (CLr) of Unlabeled Idasanutlin [Time Frame: 0 hr predose, 1, 3, 6, 7, 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]

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]

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]

Cumulative Amount Excreted in Feces 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]

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]

Tmax of Idasanutlin Metabolite [Time Frame: 0 hr predose, 1, 3, 6, 7, 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 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]

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]

Secondary Outcome(s)

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]

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]

Secondary ID(s)

RG7388

2015-002532-40

NP29910

Source(s) of Monetary Support

Please refer to primary and secondary sponsors