Clinical trial NCT01518985: The Impact of Intravenous Bendavia™ on Endothelial Reactivity Dysfunction in Cigarette Smoking
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-26
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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.

Primary outcomes:
measure: Analysis of variance (ANOVA) between group mean endothelial function (EndoPAT Index) following smoking a single cigarette with and without Bendavia
timeFrame: Baseline, +30, +60, +90 minutes post-study-drug administration start
Secondary outcomes:
measure: Anova between group mean inflammatory laboratory marker (hs-CRP; mg/L) after smoking one cigarette with and without Bendavia
timeFrame: Baseline to 24 hours post-study-drug administration
measure: ANOVA between group means of urinary 8-isoprostane (ng/mg of creatinine) after smoking one cigarette with and without Bendavia
timeFrame: Baseline to 48 hours post-study-drug administration
measure: Number adverse events with and without Bendavia
timeFrame: Baseline to Study Day 10
measure: Assessment of Bendavia exposure measured by area Under the Curve (AUC; ng*hr/mL)
timeFrame: Baseline to 48 hours post-study-drug administration
measure: ANOVA between group means of urinary 8-hydroxy-2'-deoxyguanosine (pg/mL) after smoking one cigarette with and without Bendavia
timeFrame: Baseline to 48 hours post-study-drug administration
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmaology of Miami
state: Florida
Study officials:
affiliation: Clinical Pharmacology of Miami
name: Kenneth C Lasseter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stealth Peptides
name: Richard Straube, MD
role: STUDY_DIRECTOR
References: