The Effect of Tesetaxel on the QTc Interval and the Effect of Food, Itraconazole, and Rifampin on Tesetaxel Pharmacokinetics in Patients With Advanced Solid Tumors

An Open-Label Study of the Effect of Tesetaxel on the QTc Interval and the Effect of Food, Itraconazole, and Rifampin on Tesetaxel Pharmacokinetics in Patients With Advanced Solid Tumors

This is a 3-cohort, multicenter, Phase 1 study of the effect of tesetaxel, an investigational, orally administered taxane, on the corrected QT (QTc) interval and the potential effect of food, a cytochrome P450 (CYP) 3A inhibitor (itraconazole), and a CYP3A inducer (rifampin) on tesetaxel pharmacokinetics (PK) in adult patients with advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Tesetaxel; Drug: Itraconazole; Drug: Rifampin

Detailed Description

Cohort 1:

Cohort 1 is a 2-period, 2-sequence, crossover study designed to assess the effect of food on the PK of tesetaxel and tesetaxel metabolites. Patients were randomized in a 1:2 ratio to receive tesetaxel on Day 1 of two 21-day cycles under fed and fasting conditions in one of two opposing sequences (Sequence 1A and Sequence 1B).

Cohort 2:

Cohort 2 is a 2-period, single-sequence, crossover study designed to assess the potential PK drug-drug interaction (DDI) of a strong CYP3A inhibitor (itraconazole) on tesetaxel and tesetaxel metabolites. Patients receive tesetaxel during Cycle 1 followed by a reduced dose of tesetaxel plus itraconazole during Cycle 2.

Cohort 3:

Cohort 3 is a 2-period, single-sequence, crossover study designed to assess the potential PK DDI of a strong CYP3A inducer (rifampin) on tesetaxel and tesetaxel metabolites. Patients receive tesetaxel during Cycle 1 followed by tesetaxel plus rifampin during Cycle 2.

Patients in all cohorts also participate in a study designed to assess the effect of tesetaxel and tesetaxel metabolites on cardiac repolarization as measured by the change from baseline in the QTc interval over the first cycle of treatment. Patients who are tolerating and benefitting from treatment with tesetaxel have the opportunity to continue onto an optional treatment extension.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Start Midwest
  • Texas
    • Dallas, Texas, United States, 75320
      • Mary Crowley Cancer Research
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female or male patients at least 18 years of age
• Histologically or cytologically confirmed solid tumor
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Adequate cardiac conduction by ECG
• Adequate bone marrow, hepatic, and renal function

Exclusion Criteria:

• Presence of risk factors for QTc prolongation
• Presence of neuropathy Grade > 1
• Anticancer treatment ≤ 14 days prior to randomization
• Major surgery ≤ 28 days prior to randomization

• Less than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of:

  • A moderate or strong inhibitor or inducer of CYP3A
  • A CYP3A substrate with a narrow therapeutic range or that is contraindicated with either itraconazole or rifampin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1, Sequence 1A: Fed then fasted; Cycle 1: Tesetaxel on Day 1 of a 21-day cycle under fed conditions Cycle 2: Tesetaxel on Day 1 of a 21-day cycle under fasted conditions	Drug: Tesetaxel; Tesetaxel orally on Day 1 of a 21-day cycle
Experimental: Cohort 1, Sequence 1B: Fasted then fed; Cycle 1: Tesetaxel on Day 1 of a 21-day cycle under fasted conditions Cycle 2: Tesetaxel on Day 1 of a 21-day cycle under fed conditions	Drug: Tesetaxel; Tesetaxel orally on Day 1 of a 21-day cycle
Experimental: Cohort 2: Tesetaxel plus itraconazole; Cycle 1: Tesetaxel on Day 1 of a 21-day cycle Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and itraconazole on Day -3 through Day 14 of a 21-day cycle	Drug: Tesetaxel; Tesetaxel orally on Day 1 of a 21-day cycle; Drug: Itraconazole; Itraconazole orally once daily from Day -3 to Day 14 of a 21-day cycle
Experimental: Cohort 3: Tesetaxel plus rifampin; Cycle 1: Tesetaxel on Day 1 of a 21-day cycle Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and rifampin on Day -6 through Day 14 of a 21-day cycle	Drug: Tesetaxel; Tesetaxel orally on Day 1 of a 21-day cycle; Drug: Rifampin; Rifampin orally once daily from Day -6 to Day 14 of a 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All Cohorts: The change from baseline in Fridericia's corrected QT (ΔQTcF) interval	Approximately 3 weeks
Cohort 1, Sequences 1A and 1B: Maximum observed plasma concentration (Cmax) for tesetaxel under fed and fasted conditions	Approximately 6 weeks
Cohort 1, Sequences 1A and 1B: Area under the plasma concentration-time curve from 0 to the last measurable plasma concentration (AUC0-t) for tesetaxel under fed and fasted conditions	Approximately 6 weeks
Cohort 2: Cmax for tesetaxel in the presence and absence of itraconazole	Approximately 6 weeks
Cohort 2: AUC from 0 to 336 hours (AUC0-336h) for tesetaxel in the presence and absence of itraconazole	Approximately 6 weeks
Cohort 3: Cmax for tesetaxel in the presence and absence of rifampin	Approximately 6 weeks
Cohort 3: AUC0-336h for tesetaxel in the presence and absence of rifampin	Approximately 6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
All Cohorts: Cmax for tesetaxel metabolites	Approximately 6 weeks
All Cohorts: AUC for tesetaxel metabolites	Approximately 6 weeks
All Cohorts: Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)	Baseline through 30 days after last administration of Study treatment

Collaborators and Investigators

• Sponsor: Odonate Therapeutics, Inc.
• Investigators: Study Director: Joseph O'Connell, M.D., Odonate Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2020
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): June 15, 2021

Study Registration Dates

• First Submitted: March 13, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: PK; food effect; advanced solid tumor; drug-drug interaction; rifampin; itraconazole; tesetaxel; QTc interval; food-drug interaction; tesetaxel metabolites
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole
• Other Study ID Numbers: ODO-TE-S101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No