The Impact of Intravenous Bendavia™ on Endothelial Reactivity Dysfunction in Cigarette Smoking

NCT01518985 | Completed Phase 1

• 1 other identifier: SPIRI-120
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a phase 1 randomized, double-blind, 2-period, 2-sequence crossover trial enrolling 6 healthy volunteers to assess the impact of IV-administered Bendavia on the endothelial dysfunction induced by a single cigarette.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Analysis of variance (ANOVA) between group mean endothelial function (EndoPAT Index) following smoking a single cigarette with and without Bendavia

  Endothelial function will be determined using EndoPAT 2000 (Itamar Medical Ltd) prior to and after smoking of one unfiltered cigarette and prior to and after initiation of study drug. Group comparison of endothelial function (EndoPAT Index) between placebo and active study drug within a subject will be performed. EndoPAT quantifies the endothelium-mediated changes in vascular tone. A post-occlusion to pre-occlusion ratio is calculated providing the EndoPAT index.

  Baseline, +30, +60, +90 minutes post-study-drug administration start

Secondary Outcomes (5)

• Anova between group mean inflammatory laboratory marker (hs-CRP; mg/L) after smoking one cigarette with and without Bendavia

  Baseline to 24 hours post-study-drug administration

• ANOVA between group means of urinary 8-isoprostane (ng/mg of creatinine) after smoking one cigarette with and without Bendavia

  Baseline to 48 hours post-study-drug administration

• Number adverse events with and without Bendavia

  Baseline to Study Day 10

• Assessment of Bendavia exposure measured by area Under the Curve (AUC; ng*hr/mL)

  Baseline to 48 hours post-study-drug administration

• ANOVA between group means of urinary 8-hydroxy-2'-deoxyguanosine (pg/mL) after smoking one cigarette with and without Bendavia

  Baseline to 48 hours post-study-drug administration

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Intravenous infusion of saline (0.9%) for 4 hours with smoking of one unfiltered cigarette at 30 minutes post-study-drug administration start

Drug: Sterile saline (0.9%); Other: Cigarette smoking

Bendavia

EXPERIMENTAL

Intravenous infusion of Bendavia (0.25mg/kg/hr) for 4 hours with smoking of one unfiltered cigarette at 30 minutes post-study-drug administration start

Drug: Bendavia; Other: Cigarette smoking

Interventions

Bendavia DRUG

Bendavia for infusion Intravenous infusion (0.25mg/kg/hr) for 4 hours

Bendavia

Sterile saline (0.9%) DRUG

Sterile saline for infusion (0.9%) Intravenous infusion for 4 hours

Placebo

Cigarette smoking OTHER

One unfiltered cigarette will be smoked at approximately 30 minutes post-study-drug administration start.

Bendavia; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Healthy adult male smokers between 18 and 65 years of age with signed informed consent

You may not qualify if:

• Serum sodium level below the lower limit of sites' clinical laboratory normal range at screening, D-1 and 6
• Cholesterol level ≥ 240 mg/dL
• Hypertension (blood pressure SBP \> 140, DBP \> 90 mmHg)
• Body mass index \< 18 or \> 32 kg/m2,
• Creatinine clearance calculated by the Cockcroft and Gault method calculated to be \< 90 mL/min,
• Additional laboratory abnormalities determined as clinically significant by the Principal Investigator at laboratory screening
• Clinically significant abnormalities on physical examination,
• History or evidence of renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) system dysfunction,
• History of seizures or history of epilepsy,
• History of serious (Principal Investigator judgment) mental illness,
• Receipt of investigational medicinal product within 30 days prior to the planned date of study drug administration,
• Positive serology for human immunodeficiency virus type 1 or 2, or hepatitis B surface antigen,
• Fever \> 37.5°C at the time of planned dosing,
• Suspicion, or recent history, of alcohol or substance abuse,
• Donated blood or blood products within the past 30 days,

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (1)

Clinical Pharmaology of Miami

Miami, Florida, 33014-3616, United States

Location

MeSH Terms

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide

Study Officials

• Kenneth C Lasseter, MD

  Clinical Pharmacology of Miami

  PRINCIPAL INVESTIGATOR

• Richard Straube, MD

  Stealth Peptides

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2012
• First Posted: January 26, 2012
• Study Start: January 1, 2012
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: April 19, 2012

Record last verified: 2012-04

Locations

US (1)