Study to Assess the Pharmacodynamic Effects of Unfractionated Heparin (UFH) in Healthy Volunteers With and Without Bendavia

NCT01513200 | Completed Phase 1

• 1 other identifier: SPIRI-155
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a phase 1 randomized, double-blind crossover trial enrolling approximately 12 healthy volunteers to assess whether intravenous (IV) UFH and IV Bendavia administered together have any significant impact on the pharmacodynamic effects of UFH and the pharmacokinetics of Bendavia.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Mean difference over 24 hours in aPTT (activated partial prothrombin time) in seconds when UFH is administered with and without Bendavia

  Difference in group (with/without Bendavia) means of aPPT values will be assessed for statistical significance (Analysis of Variance; ANOVA) at the following time points: Pre-UFH, Pre-Study-Drug infusion start and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours Post-Study-Drug infusion start.

  Pre-UFH to 24 hours post-study drug administration

Secondary Outcomes (3)

• Mean difference over 12 hours of anti-factor Xa (IU/mL) when UFH is administered with and without Bendavia

  Pre-UFH to 12 hours post-study drug administration

• Mean difference in Bendavia Area Under the Curve(0-infinity) (AUC) when Bendavia is administered with and without UFH (historical data will be used to provide bendavia without UFH)

  48 hours post-study-drug administration

• Difference in number of adverse events when UFH is administered with and without Bendavia

  Pre-dose through Day 10

Study Arms (2)

UFH + Placebo

PLACEBO COMPARATOR

UFH (60U/kg bolus followed by 12U/kg/hr for approx.11 hours) with saline (placebo) administered as infusion for the last 4 hours of UFH

Drug: Unfractionated heparin (UFH); Drug: Saline (0.9%, sterile, for infusion)

UFH + Bendavia

EXPERIMENTAL

UFH (60U/kg bolus followed by 12U/kg/hr for approx.11 hours) with Bendavia (0.25mg/kg/hr) administered as infusion for the last 4 hours of UFH

Drug: Unfractionated heparin (UFH); Drug: Bendavia

Interventions

Unfractionated heparin (UFH) DRUG

UFH solution for infusion Initially 60U/kg bolus followed by intravenous infusion (12U/kg/hr) for approximately 11 hours

UFH + Bendavia; UFH + Placebo

Bendavia DRUG

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

UFH + Bendavia

Saline (0.9%, sterile, for infusion) DRUG

Saline (placebo) Constant IV infusion for 4 hours

UFH + Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy adult males or females aged between 18 and 65 years of age with signed informed consent.
• Women who are not post-menopausal (without menstrual bleed for \>24 months) or surgically sterile must have a negative serum pregnancy test at screening and within 24 hours of treatment with understanding (through informed consent process) to not become pregnant over the duration of the study and must agree to employ an effective form of birth control for the duration of the study \[Acceptable forms of birth control are: double-barrier contraceptives (condom, diaphragm with spermicide) or intra-uterine device (IUD) 1 week prior to and at least 30 days post treatment even if hormonal contraceptives are used\]

You may not qualify if:

• Serum sodium level below the lower limit of the site's clinical laboratory normal range at both study period qualification visits,
• Platelet value below the lower limit of normal range at screening or admission,
• aPTT value outside the normal range at screening or admission,
• Creatinine clearance calculated by the Cockcroft and Gault method calculated to be \<90 mL/min for males and \<80 mL/min for females,
• Any addition laboratory abnormalities determined as clinically significant by the Principal Investigator at laboratory screening,
• Clinically significant abnormalities on physical examination,
• Body Mass Index (BMI) of less than 18 kg/m2 or greater than 32 kg/m2,
• Any disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) systems,
• History of seizures or history of epilepsy,
• History of serious (Principal Investigator judgment) mental illness,
• Receipt of investigational medicinal product within 30 days before planned date of unfractionated heparin and/or study drug administration,
• Positive serology for human immunodeficiency virus 1 or 2 (HIV1 or 2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV),
• Fever greater than 37.5°C at the time of planned dosing,
• Suspicion of 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 Pharmacology of Miami

Miami, Florida, 33014-3616, United States

Location

MeSH Terms

Interventions

Heparin; arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; Sodium Chloride

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

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 6, 2012
• First Posted: January 20, 2012
• Study Start: January 1, 2012
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 19, 2012

Record last verified: 2012-04

Locations

US (1)