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

Primary Purpose

Hematologic Malignancies, Solid Tumors

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

omacetaxine mepesuccinate

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring omacetaxine, omacetaxine mepesuccinate, pharmacokinetics, hematologic malignancies, advanced solid tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Teva Investigational Site 38045

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

omacetaxine mepesuccinate

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum observed plasma drug concentrations (Cmax)

Time to Reach Maximum Observed Plasma Drug Concentration (Tmax)

Area under the plasma concentration by time curve (AUC) from time 0 to infinity (AUC0-∞)

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)

Terminal rate constant (λz) and associated half-life (t½)

Percentage extrapolation calculated as (AUC0-∞-AUC0-t)/(AUC0-∞)x100

Apparent plasma clearance (CL/F)

Apparent volume of distribution (Vz/F)

Secondary Outcome Measures

Summary of participants with adverse events

Full Information

NCT ID

NCT01844869

First Posted

April 29, 2013

Last Updated

January 29, 2015

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01844869

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

December 2014 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancies, Solid Tumors

Keywords

omacetaxine, omacetaxine mepesuccinate, pharmacokinetics, hematologic malignancies, advanced solid tumors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

omacetaxine mepesuccinate

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

omacetaxine mepesuccinate

Other Intervention Name(s)

omacetaxine

Primary Outcome Measure Information:

Title

Maximum observed plasma drug concentrations (Cmax)

Time Frame