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Single Ascending Dose of GAP-134 as a 24-hour IV Infusion in Healthy Japanese Males

Primary Purpose

Arrhythmia

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

GAP-134

About this trial

This is an interventional prevention trial for Arrhythmia

Eligibility Criteria

20 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria

Healthy Japanese men age 20-45.
BMI within 17.6 to 26.4 kg/m2 and body weight greater than or equal to 45 kg.
Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Must be able to abstain from smoking within 48 hours before study day 1 until the end of the inpatient confinement period.

Exclusion Criteria

Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease.
Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the test article (e.g., resection of liver, kidney, gallbladder, or gastrointestinal tract).
Acute disease state.
Any history of clinically important cardiac arrhythmias. Family history of long QT syndrome, Torsades de Pointes or unexpected cardiac death.
Any clinically important deviation from normal limits in physical examination, vital signs, 12-lead electrocardiograms (ECGs), or clinical laboratory test results. Creatinine levels must be less than or equal to the upper limit of normal at screening.
Demonstration of a positive orthostatic test at screening. The definition of a positive test is a greater than or equal to 20 mm Hg decrease in systolic blood pressure, greater than or equal to 10 mm Hg decrease in diastolic blood pressure, or a greater than or equal to 30 bpm increase in pulse rate, after standing for 3 minutes.
Positive serologic findings for human immunodeficiency virus (HIV) antigen and antibodies, hepatitis B surface antigen (HbsAg), and/or hepatitis C virus (HCV) antibodies.
Positive findings of urine drug screen.
History of any clinically important drug allergy or adverse drug reaction (e.g., relapsing dermatitis, drug hypersensitivity, drug allergy, hypersensitivity to ingredient in the test articles or angioedemas)
Use of any investigational drug within 90 days before study day 1 or prescription drug within 30 days before study day 1.
Consumption of any caffeine-containing products.
Consumption of grapefruit or grapefruit-containing products within 72 hours before study day 1 until the end of the inpatient confinement period.
Use of any over-the-counter drugs, including herbal supplements (except for the occasional use of vitamins less than or equal to 100% of the recommended daily allowance), within 14 days before study day 1.

Sites / Locations

Outcomes

Primary Outcome Measures

The primary objective is to assess the safety and tolerability of ascending, single IV doses of GAP-134 as 24-hour continuous infusions and as a single bolus injection in healthy Japanese male subjects.

Secondary Outcome Measures

The secondary objective is to provide the initial PK profiles of ascending single IV doses (24 hour and 1-minute) of GAP-134 taken under fasting conditions in healthy Japanese male subjects.

Full Information

NCT ID

NCT00543946

First Posted

October 11, 2007

Last Updated

September 25, 2018

Sponsor

Wyeth is now a wholly owned subsidiary of Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00543946

Brief Title

Single Ascending Dose of GAP-134 as a 24-hour IV Infusion in Healthy Japanese Males

Official Title

Ascending Single Dose Study of The Safety, Tolerability, Pharmacokinetics, of GAP-134 Administered Intravenously as a 24-Hour Infusion to Healthy Japanese Male Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

October 2007 (undefined)

Primary Completion Date

March 2008 (Actual)

Study Completion Date

March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

5. Study Description

Brief Summary

This is a study of GAP-134, an antiarrhythmic di-peptide. This study will provide an initial assessment of the safety, tolerability, and pharmacokinetics (PK) of GAP-134 after administration of ascending single intravenous (IV) doses to healthy Japanese male subjects.

Detailed Description

Atrial Fibrillation (AF) is the most commonly occurring sustained arrhythmia in clinical practice. AF is a serious disorder associated with an increased risk of stroke, morbidity and mortality, and the number of patients is estimated to double within the next 4 decades. The currently available antiarrhythmic drugs have limited efficacy and are associated with serious side effects of which potentially lethal ventricular proarrhythmias are one of the major concerns. Thus, there is a large unmet clinical need for efficacious and safe antiarrhythmic drugs for the treatment of AF. The classical orientation of antiarrhythmic therapy has been to modulate cardiac ion channels (sodium, potassium or calcium) or the autonomic nervous system. However, numerous experimental and clinical studies have suggested that cardiac conduction slowing and impaired gap junction intercellular communication (GJIC) are important in the pathogenesis of cardiac arrhythmias, including AF. General conduction slowing or the presence of small islands of intra-atrial conduction block resulting from a decreased gap junction conductance, altered gap junction expression and heterogeneous spatial distribution of gap junctions may provide turning points for the multiple waves, and thereby promote re-entry of impulses. In recognition of this, several authors have proposed gap junction modulation as a potential new target in the treatment of AF. GAP-134 is an antiarrhythmic dipeptide that has demonstrated in vitro and in vivo efficacy in mouse and dog models of arrhythmia. GAP-134 has no apparent proarrhythmic activity or hemodynamic compromise and does not show any significant binding in a panel of >60 different receptors and ion channels. If determined to be safe and effective the indication sought for GAP-134 will be the prevention of post operative atrial fibrillation.

6. Conditions and Keywords

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

Arrhythmia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

56 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

GAP-134

Intervention Description

24-Hour IV infusion, SAD

Primary Outcome Measure Information:

Title

Time Frame

6 months

Secondary Outcome Measure Information:

Title

The secondary objective is to provide the initial PK profiles of ascending single IV doses (24 hour and 1-minute) of GAP-134 taken under fasting conditions in healthy Japanese male subjects.

Time Frame

6 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Healthy Japanese men age 20-45. BMI within 17.6 to 26.4 kg/m2 and body weight greater than or equal to 45 kg. Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Must be able to abstain from smoking within 48 hours before study day 1 until the end of the inpatient confinement period. Exclusion Criteria Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the test article (e.g., resection of liver, kidney, gallbladder, or gastrointestinal tract). Acute disease state. Any history of clinically important cardiac arrhythmias. Family history of long QT syndrome, Torsades de Pointes or unexpected cardiac death. Any clinically important deviation from normal limits in physical examination, vital signs, 12-lead electrocardiograms (ECGs), or clinical laboratory test results. Creatinine levels must be less than or equal to the upper limit of normal at screening. Demonstration of a positive orthostatic test at screening. The definition of a positive test is a greater than or equal to 20 mm Hg decrease in systolic blood pressure, greater than or equal to 10 mm Hg decrease in diastolic blood pressure, or a greater than or equal to 30 bpm increase in pulse rate, after standing for 3 minutes. Positive serologic findings for human immunodeficiency virus (HIV) antigen and antibodies, hepatitis B surface antigen (HbsAg), and/or hepatitis C virus (HCV) antibodies. Positive findings of urine drug screen. History of any clinically important drug allergy or adverse drug reaction (e.g., relapsing dermatitis, drug hypersensitivity, drug allergy, hypersensitivity to ingredient in the test articles or angioedemas) Use of any investigational drug within 90 days before study day 1 or prescription drug within 30 days before study day 1. Consumption of any caffeine-containing products. Consumption of grapefruit or grapefruit-containing products within 72 hours before study day 1 until the end of the inpatient confinement period. Use of any over-the-counter drugs, including herbal supplements (except for the occasional use of vitamins less than or equal to 100% of the recommended daily allowance), within 14 days before study day 1.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Wyeth is now a wholly owned subsidiary of Pfizer

Official's Role

Study Director

Facility Information:

City

Shinagawa-Ku

State/Province

Tokyo

ZIP/Postal Code

141-0001

Country

Japan

12. IPD Sharing Statement

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Single Ascending Dose of GAP-134 as a 24-hour IV Infusion in Healthy Japanese Males

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