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

NCT01844869 | Completed Phase 1

• 2 other identifiers: C41443/1103 Study2012-004003-12
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematologic Malignancies; Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (1)

• 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)

Study Arms (1)

omacetaxine mepesuccinate

EXPERIMENTAL

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

Interventions

omacetaxine mepesuccinate DRUG

Also known as: omacetaxine

omacetaxine mepesuccinate

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Teva Investigational Site 38045

Amsterdam, Netherlands

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Homoharringtonine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Design

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

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 1, 2013
• Study Start: July 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: January 1, 2015
• Last Updated: January 30, 2015

Record last verified: 2015-01

Locations

NL (1)