A Study to Define the ECG Effects of Lixivaptan Compared to Placebo and Moxifloxacin in Healthy Adult Men and Women: A Thorough ECG Study

A Double Blind, Randomized, Repeat-Dose, Parallel Group Study to Define the ECG Effects of Lixivaptan Using a Clinical and a Supratherapeutic Dose, Compared to Placebo and Moxifloxacin (a Positive Control), in Healthy Adult Men and Women: A Thorough ECG Study

This is a Phase 1, double-blind, randomized, repeat-dose, single -dite, 4-arm parallel group study to define the ECG effect of lixivaptan using a therapeutic and supratherapeutic dose compared to placebo and moxifloxacin (a positive control in healthy adult men and women.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: placebo; Drug: lixivaptan; Drug: moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 298
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Research Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy males or females, between 18 and 45 years of age, inclusive
2. Body mass index (BMI; see 279HAPPENDIX B) within 18 to 32 kg/m2, inclusive
3. Absence of significant disease as determined by medical history, physical examination, laboratory evaluations, 12-lead ECG, and vital signs (conducted at Screening or on admission to the clinic)
4. Normal 12-lead ECG with no clinically significant abnormalities of rate, rhythm, or conduction (i.e., normal PR interval of 0.12-0.2 sec, normal QRS duration of 0.06-0.1 sec, and a QTc Bazett <440 ms for males or <470 ms for females)
5. Clinical laboratory evaluations (including a serum chemistry panel [fasted at least 8 hours], CBC, and UA) within the reference range for the test laboratory. Laboratory findings outside the normal reference range may be repeated once; The subject may be enrolled if laboratory findings outside the normal reference range are deemed not clinically significant by the investigator
6. Negative test for selected drugs of abuse (280HAPPENDIX A) at Screening and at Check-in
7. Women must be postmenopausal (more than 12 months since last period, verified by FSH and estradiol measurements); surgically sterile (hysterectomy or tubal ligation at least 6 months prior to enrollment); or be using an intrauterine device (including hormone-impregnated devices), or double barrier (i.e. diaphragm plus spermicide) non-hormonal contraceptive therapy for the duration of the study; and must have a negative serum pregnancy test at Screening and Check-in
8. Able to communicate effectively with study personnel
9. Be adequately informed of the nature and risks of the study and able to comprehend and sign an Informed Consent Form (ICF) prior to any study related procedures.

Exclusion Criteria:

1. Known hypersensitivity or allergy to lixivaptan (VPA-985), other vasopressin antagonists, moxifloxacin, or any other fluoroquinolones;
2. Women who are pregnant or breast feeding
3. A first degree relative with Long QT Syndrome or a family history of unexplained sudden death
4. Any history, disease or condition (medical or surgical) which, in the opinion of the investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, urological, neurological, psychiatric, or central nervous system; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of study drug, or would place the subject at increased risk
5. History of unexplained syncope
6. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
7. History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically significant
8. Screening systolic blood pressure <90 mmHg or >140 mmHg, and/or diastolic blood pressure >90 mmHg
9. Screening heart rate >90 beats per minute
10. Positive screen for hepatitis B (HBsAg), hepatitis C (anti-HCV), or HIV (anti-HIV)
11. Participation in any other investigational study within 30 days prior to Check-in
12. Any history of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction within 6 months prior to Check-in
13. A history of difficulty with donating blood
14. Donation of ≥ 500 mL blood or blood products within 45 days prior to enrollment
15. Receipt of blood products within 2 months prior to Check-in
16. Use of any of the medications in 281HTable 3 within the given timeframe prior to Check-in:

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: A; Placebo by mouth	Drug: placebo; capsules
Experimental: B; lixivaptan	Drug: lixivaptan; capsules
Active Comparator: C; moxifloxacin	Drug: moxifloxacin; tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Timed-matched, placebo-corrected, changed from Baseline in QTc	7days

Collaborators and Investigators

• Sponsor: CardioKine Inc.
• Collaborators: Biogen; Cardiokine Biopharma, LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: May 8, 2008
• First Submitted That Met QC Criteria: May 9, 2008
• First Posted (Estimate): May 12, 2008

Study Record Updates

• Last Update Posted (Estimate): June 21, 2011
• Last Update Submitted That Met QC Criteria: June 20, 2011
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: To determine whether lixivaptan administration at supratherapeutic or therapeutic doses results in the prolongation of the QTc interval.
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: CK-LX1403