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

Phase 1

Completed

• Conditions: Arrhythmia

• Registration Number: NCT00543946
• Lead Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer

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.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2007-10-11
• Study First Submitted QC: 2007-10-11
• Study First Posted: 2007-10-15
• Primary Completion: 2008-03
• Study Completion: 2008-03
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-25
• Last Update Posted: 2018-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 56

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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.	6 months

Secondary Outcome Measures

Name	Time	Method
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.	6 months