An Open-Label Study to Investigate the Pharmacokinetics of Omacetaxine Mepesuccinate

An Open-Label Study to Investigate the Pharmacokinetics (Absorption, Distribution, Metabolism, and Excretion) of Omacetaxine Mepesuccinate Following Subcutaneous Administration of [14C]Omacetaxine Mepesuccinate in Patients With Relapsed and/or Refractory Hematologic Malignancies or Advanced Solid Tumors

The purpose of this study is to determine the pharmacokinetic and safety profiles of omacetaxine and its metabolites in patients with relapsed and/or refractory hematologic malignancies or advanced solid tumors following subcutaneous (sc) administration.

Study Overview

• Status: Completed
• Conditions: Solid Tumors; Hematologic Malignancies
• Intervention / Treatment: Drug: omacetaxine mepesuccinate

Detailed Description

This is a Phase 1, single-center, open-label, nonrandomized study to determine the pharmacokinetics (absorption, distribution, metabolism, and excretion) of omacetaxine and its metabolites following a sc dosage of 1.25 mg/m2 in adult patients with relapsed and/or refractory hematologic malignancies or advanced solid tumors. The study consists of a screening period of up to 28 days, followed by a 7-day pharmacokinetic assessment period (period A) that includes administration of a single radiolabeled dose of omacetaxine, an open-label treatment period of up to six 28-day cycles (period B), and a final assessment to occur approximately 28±7 days after the end of the last treatment cycle. Period B will begin after collection of the 72-hour pharmacokinetic sample during period A.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Teva Investigational Site 38045

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:

• Written informed consent is obtained.
• The patient is at least 18 years of age at the time of informed consent.
• The patient has a histologically or cytologically confirmed diagnosis of any of the following:
• Relapsed or refractory leukemia, including Philadelphia chromosome-positive (Ph+), chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), acute myelogenous leukemia (AML), or myelodysplastic syndrome (MDS).
• Advanced solid tumors (ie, breast, lung, head/neck, colorectal, melanoma, and sarcoma). The malignancy must be considered unresponsive to accepted available therapies.
• The patient has an estimated life expectancy of at least 3 months.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Other criteria apply.

Exclusion Criteria:

• The patient has had chemotherapy, radiotherapy, radioimmunotherapy, or immunotherapy within 28 days prior to the first dose of study drug or has not recovered from adverse events due to any agents administered previously. For patients who received therapy with mitomycin C, the interval is 42 days.
• The patient is receiving any other treatment for hematologic/nonhematologic malignancy.
• The patient has had previous treatment with omacetaxine.
• The patient has been treated with any hematopoietic growth factors within 14 days of study entry (patients on chronic erythropoiesis stimulating agents are allowed).
• The patient has New York Heart Association (NYHA) Class 3 or 4 heart disease, active ischemia, or any uncontrolled, unstable cardiac condition for which treatment for the condition is indicated but is not controlled despite adequate therapy, including angina pectoris, cardiac arrhythmia, hypertension, or congestive heart failure.
• The patient has experienced a myocardial infarction within the previous 12 weeks.
• The patient has a solid tumor with symptomatic central nervous system (CNS) metastases.
• The patient has an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment.
• Other criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: omacetaxine mepesuccinate; Period A: 7-day pharmacokinetic assessment period in which all patients will be administered a single subcutaneous radiolabeled dose of 1.25-mg/m2 omacetaxine. Period B: omacetaxine will be administered as an sc injection at a dosage of 1.25 mg/m2 twice daily for 7 days (patients with solid tumors) or 14 days (patients with hematologic malignancies) of every 28-day cycle for up to 6 cycles.

Drug: omacetaxine mepesuccinate; Other Names: omacetaxine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma drug concentrations (Cmax)		0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose
Time to Reach Maximum Observed Plasma Drug Concentration (Tmax)		0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose
Area under the plasma concentration by time curve (AUC) from time 0 to infinity (AUC0-∞)		0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose
Area under the Curve from Time Zero to the Time of the Last Measurable Drug Concentration (AUC0-t)	AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)	0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose
Terminal rate constant (λz) and associated half-life (t½)		0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose
Percentage extrapolation calculated as (AUC0-∞-AUC0-t)/(AUC0-∞)x100		0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose
Apparent plasma clearance (CL/F)		0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose
Apparent volume of distribution (Vz/F)		0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Summary of participants with adverse events	From Day 1 through the end of the follow-up period (28±7 days after 6 month treatment cycle)

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: April 29, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (Estimate): May 1, 2013

Study Record Updates

• Last Update Posted (Estimate): January 30, 2015
• Last Update Submitted That Met QC Criteria: January 29, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: pharmacokinetics; advanced solid tumors; hematologic malignancies; omacetaxine; omacetaxine mepesuccinate
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Protein Synthesis Inhibitors; Homoharringtonine
• Other Study ID Numbers: C41443/1103 Study; 2012-004003-12 (EudraCT Number)