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

NCT04312282 | Terminated Phase 1 FDA Drug

• 1 other identifier: ODO-TE-S101
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Advanced Solid Tumors

Keywords

tesetaxel; itraconazole; rifampin; food effect; QTc interval; food-drug interaction; drug-drug interaction; PK; tesetaxel metabolites; advanced solid tumor

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (3)

• 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

Study Arms (4)

Cohort 1, Sequence 1A: Fed then fasted

EXPERIMENTAL

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

Cohort 1, Sequence 1B: Fasted then fed

EXPERIMENTAL

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

Cohort 2: Tesetaxel plus itraconazole

EXPERIMENTAL

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; Drug: Itraconazole

Cohort 3: Tesetaxel plus rifampin

EXPERIMENTAL

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; Drug: Rifampin

Interventions

Tesetaxel DRUG

Tesetaxel orally on Day 1 of a 21-day cycle

Cohort 1, Sequence 1A: Fed then fasted

Itraconazole DRUG

Itraconazole orally once daily from Day -3 to Day 14 of a 21-day cycle

Cohort 2: Tesetaxel plus itraconazole

Rifampin DRUG

Rifampin orally once daily from Day -6 to Day 14 of a 21-day cycle

Cohort 3: Tesetaxel plus rifampin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Odonate Therapeutics, Inc.: lead

Study Sites (3)

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75320, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

tesetaxel; Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Joseph O'Connell, M.D.

  Odonate Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: March 18, 2020
• Study Start: March 6, 2020
• Primary Completion: September 30, 2020
• Study Completion: June 15, 2021
• Last Updated: July 28, 2021

Record last verified: 2021-07

Locations

US (3)