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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

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ClinicalTrials.gov Identifier: NCT04312282
Recruitment Status : Active, not recruiting
First Posted : March 18, 2020
Last Update Posted : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
Odonate Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: Tesetaxel Drug: Itraconazole Drug: Rifampin Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 93 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 6, 2020
Actual Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. All Cohorts: The change from baseline in Fridericia's corrected QT (ΔQTcF) interval [ Time Frame: Approximately 3 weeks ]
  2. Cohort 1, Sequences 1A and 1B: Maximum observed plasma concentration (Cmax) for tesetaxel under fed and fasted conditions [ Time Frame: Approximately 6 weeks ]
  3. 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 [ Time Frame: Approximately 6 weeks ]
  4. Cohort 2: Cmax for tesetaxel in the presence and absence of itraconazole [ Time Frame: Approximately 6 weeks ]
  5. Cohort 2: AUC from 0 to 336 hours (AUC0-336h) for tesetaxel in the presence and absence of itraconazole [ Time Frame: Approximately 6 weeks ]
  6. Cohort 3: Cmax for tesetaxel in the presence and absence of rifampin [ Time Frame: Approximately 6 weeks ]
  7. Cohort 3: AUC0-336h for tesetaxel in the presence and absence of rifampin [ Time Frame: Approximately 6 weeks ]

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


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04312282


Locations
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United States, Michigan
START Midwest
Grand Rapids, Michigan, United States, 49546
United States, Texas
Mary Crowley Cancer Research
Dallas, Texas, United States, 75320
NEXT Oncology
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Odonate Therapeutics, Inc.
Investigators
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Study Director: Joseph O'Connell, M.D. Odonate Therapeutics, Inc.
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Responsible Party: Odonate Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04312282    
Other Study ID Numbers: ODO-TE-S101
First Posted: March 18, 2020    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Odonate Therapeutics, Inc.:
tesetaxel
itraconazole
rifampin
food effect
QTc interval
food-drug interaction
drug-drug interaction
PK
tesetaxel metabolites
advanced solid tumor
Additional relevant MeSH terms:
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Neoplasms
Itraconazole
Rifampin
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers