A Double-Blind Study in Healthy Volunteers to Assess the Effect of E7080 on the QTc Interval

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01525394
First received: January 31, 2012
Last updated: May 20, 2013
Last verified: April 2012
  Purpose

This is a double-blind (vis-à-vis E7080), randomized, placebo-controlled, three-treatment, three-way crossover study in healthy subjects. There are two phases in this study: Pre-Randomization and Randomization. The Pre-Randomization Phase consists of Screening and Baseline Period 1. The Randomization Phase consists of five periods: Treatment Period 1, Baseline Period 2, Treatment Period 2, Baseline Period 3, and Treatment Period 3. Completion of study termination procedures will be performed at Visit 11.


Condition Intervention Phase
Refractory Solid Tumors
Lymphomas
Drug: E7080
Drug: Moxifloxacin 400 mg
Drug: Placebos (matched to 4 mg and 10 mg E7080 capsules).
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Official Title: A Double-Blind Study in Healthy Volunteers to Assess the Effect of E7080 on the QTc Interval

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • To evaluate the potential for QT/QTc prolongation by 32 mg E7080 using a placebo control and moxifloxacin as the positive control. [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the safety of E7080 in healthy subjects. [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Enrollment: 52
Study Start Date: December 2010
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E7080 Capsules Drug: E7080
32 mg will be administered orally as three 4 mg and two 10 mg capsules as a single dose.
Active Comparator: Moxifloxacin tablets Drug: Moxifloxacin 400 mg
Moxifloxacin 400 mg will be administered orally as one 400 mg tablet.
Placebo Comparator: Placebos Drug: Placebos (matched to 4 mg and 10 mg E7080 capsules).
The Placebo dose will consist of three 4 mg and two 10 mg placebo capsules.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be included in this study:

  1. Normal, healthy male and female subjects ≥ 18 years of age at the time of informed consent.
  2. All females must have a negative serum human chorionic gonadotropin (hCG) pregnancy test result at Screening and Baseline. Females of child-bearing potential must agree to use a medically acceptable method of contraception (e.g., abstinence, an intrauterine device (IUD), a double-barrier method such as condom + spermicide or condom + diaphragm with spermicide, a contraceptive implant, an oral contraceptive or have a vasectomized partner) throughout the entire study period and for 30 days after study drug discontinuation. The only subjects who will be exempt from this requirement are postmenopausal women (defined as greater than age 50 and at least 12 months of amenorrhea) or subjects who have been sterilized surgically or who are otherwise proven sterile (e.g., bilateral tubal ligation with surgery at least 6 months prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 2 months prior to dosing). All women who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 12 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
  3. Male patients who are not abstinent or have undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use a highly affective method of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously).
  4. Partners of male and female subjects must use an effective method of contraception (e.g., barrier method, IUD), commencing prior to or at initiation of study drug and continuing for the duration of the study and for 30 days after study drug discontinuation. All females who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 12 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
  5. Voluntarily provide written informed consent prior to any study procedures.
  6. Are willing and able to comply with all aspects of the protocol for the duration of the study.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participation in the study:

  1. Subjects with any clinically significant abnormality, including a QTc interval of > 450 msec, on 12-lead ECG at the time of the Screening Period, Baseline Periods, or 30 minutes before administration of study drug.
  2. A history of myocardial infarction, syncope or cardiac arrhythmias.
  3. A history of uncontrolled hypertension, defined as a systolic pressure of >140 mm Hg and diastolic pressure of > 90 mm Hg.
  4. A history of unstable heart disease or additional risk factors for Torsades de Pointes (TdP) including heart failure, hypokalemia, or a family history of congenital long QT syndrome or unexplained cardiac arrest.
  5. Subjects with a history of gastrointestinal surgery (hepatectomy, nephrotomy, digestive organ resection, etc.) that may affect PK profiles of E7080.
  6. Known intolerance to the study drug or moxifloxacin (Avelox) (or any of the excipients).
  7. A positive result from human immunodeficiency virus (HIV), hepatitis A antibody (HAVAb), hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb) tests at Screening.
  8. A known or suspected history of drug or alcohol misuse within 6 months prior to Screening, or who have a positive urine drug test or breath alcohol test at Screening.
  9. Subjects who participated in another clinical trial of an investigational drug or device within 4 weeks prior to dosing.
  10. Subjects who received blood products within 4 weeks, or donated blood within 8 weeks, or donated plasma within one week of dosing.
  11. Subjects who have engaged in heavy exercise within 2 weeks prior to check-in (e.g., marathon runners, weight lifters, etc.).
  12. Females who are pregnant or breastfeeding.
  13. Subjects who are unwilling or unable to abide by the requirements of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525394

Locations
United States, Washington
Charles River
Tacoma, Washington, United States, 98418
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Robert Shumaker Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01525394     History of Changes
Other Study ID Numbers: E7080-A001-002
Study First Received: January 31, 2012
Last Updated: May 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
lymphomas
Refractory solid tumors

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014