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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01518985
First Posted: January 26, 2012
Last Update Posted: April 19, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Stealth BioTherapeutics Inc.
  Purpose
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.

Condition Intervention Phase
Healthy Volunteers Drug: Bendavia Drug: Sterile saline (0.9%) Other: Cigarette smoking Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Phase 1, Placebo-Controlled Trial to Evaluate the Impact of Intravenous (IV) Bendavia™ (MTP-131) on Endothelial Reactivity Dysfunction Induced by Cigarette Smoking

Resource links provided by NLM:


Further study details as provided by Stealth BioTherapeutics Inc.:

Primary Outcome Measures:
  • Analysis of variance (ANOVA) between group mean endothelial function (EndoPAT Index) following smoking a single cigarette with and without Bendavia [ Time Frame: Baseline, +30, +60, +90 minutes post-study-drug administration start ]

    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.



Secondary Outcome Measures:
  • Anova between group mean inflammatory laboratory marker (hs-CRP; mg/L) after smoking one cigarette with and without Bendavia [ Time Frame: Baseline to 24 hours post-study-drug administration ]
    hs-CRP will be evaluated prior to and after smoking of one unfiltered cigarette and prior to and after initiation of study drug. Group comparison of hs-CRP levels between placebo and active study drug within a subject will be performed.

  • ANOVA between group means of urinary 8-isoprostane (ng/mg of creatinine) after smoking one cigarette with and without Bendavia [ Time Frame: Baseline to 48 hours post-study-drug administration ]
    8-isoprostane will be measured prior to and after smoking of one unfiltered cigarette and prior to and after initiation of study drug. Group comparison of laboratory results between placebo and active study drug within a subject will be performed.

  • Number adverse events with and without Bendavia [ Time Frame: Baseline to Study Day 10 ]
    Adverse events will be tabulated by treatment group. No statistical analysis will be preformed.

  • Assessment of Bendavia exposure measured by area Under the Curve (AUC; ng*hr/mL) [ Time Frame: Baseline to 48 hours post-study-drug administration ]
    Bendavia levels will be measured and pharmacokinetic parameters reported.

  • ANOVA between group means of urinary 8-hydroxy-2'-deoxyguanosine (pg/mL) after smoking one cigarette with and without Bendavia [ Time Frame: Baseline to 48 hours post-study-drug administration ]
    8-hydroxy-2'-deoxyguanosine will be measured prior to and after smoking of one unfiltered cigarette and prior to and after initiation of study drug. Group comparison of laboratory results between placebo and active study drug within a subject will be performed.


Enrollment: 6
Study Start Date: January 2012
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
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%)
Sterile saline for infusion (0.9%) Intravenous infusion for 4 hours
Other: Cigarette smoking
One unfiltered cigarette will be smoked at approximately 30 minutes post-study-drug administration start.
Experimental: Bendavia
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
Bendavia for infusion Intravenous infusion (0.25mg/kg/hr) for 4 hours
Other: Cigarette smoking
One unfiltered cigarette will be smoked at approximately 30 minutes post-study-drug administration start.

  Eligibility

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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,
  • Employee or family member of the investigational site,
  • Subjects who are either unwilling to agree to refrain from use or found to be using Nicotine (or nicotine products) including cigarettes from 12 hours prior to start of each study drug infusion through to the completion of endothelial function testing, Alcohol, Caffeine, Xanthine-containing food or beverages and over-the-counter medications with the exception of Tylenol from 24 hours prior to dosing and throughout the confinement periods, Supplementary antioxidant vitamins from 7 days prior to dosing and throughout the confinement periods, Prescription medications from 14 days prior to and 7 days post treatment
  • Subjects having previous exposure to Bendavia.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01518985


Locations
United States, Florida
Clinical Pharmaology of Miami
Miami, Florida, United States, 33014-3616
Sponsors and Collaborators
Stealth BioTherapeutics Inc.
Investigators
Principal Investigator: Kenneth C Lasseter, MD Clinical Pharmacology of Miami
Study Director: Richard Straube, MD Stealth Peptides
  More Information

Responsible Party: Stealth BioTherapeutics Inc.
ClinicalTrials.gov Identifier: NCT01518985     History of Changes
Other Study ID Numbers: SPIRI-120
First Submitted: January 23, 2012
First Posted: January 26, 2012
Last Update Posted: April 19, 2012
Last Verified: April 2012