Skip to main content
OpenTrials
Completed

NCT Number: NCT02828930

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)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, H-1134, Hungary

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Idasanutlin

Drug

Idasanutlin 300 mg tablet orally on Day 1; 400 mg tablet orally on Day 11 and Day 19. Participants, who are eligible to enter in optional treatment extension phase, will continue treatment with idasanutlin 200 mg tablet orally once daily for 5 days of 28-day cycle.

Other names: RO5503781

Placebo

Drug

Placebo matching to idasanutlin aqueous dispersion will be administered orally on Day 11.

[13C]-radiolabeled Idasanutlin

Drug

[13C]-radiolabeled idasanutlin 100 mcg will be administered as IV infusion over 15-minute on Day 1.

[14C]-radiolabeled Idasanutlin

Drug

[14C]-radiolabeled idasanutlin 100 mg capsule (2, 50 mg capsules containing approximately 100 microcurie of radioactivity) will be administered orally on Day 1.

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Renal Clearance (CLr) of Unlabeled Idasanutlin

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

  9. 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

  10. 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

  11. 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

  12. Tmax of Idasanutlin Metabolite

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

  13. Cmax of Idasanutlin Metabolite

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

  14. AUC (0-inf) of Idasanutlin Metabolite

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

  15. AUC(0-last) of Idasanutlin Metabolite

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

  16. Plasma t1/2 of Idasanutlin Metabolite

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

  17. 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

  18. CL/F of Idasanutlin Metabolite

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

  19. CLr of Idasanutlin Metabolite

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

  20. Vz/F of Idasanutlin Metabolite

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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

Secondary outcomes

  1. 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)

  2. 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

  3. 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

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Jul 12, 2016
Registry last updated
Dec 18, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.