A Phase 1 Study Examining the Pharmacokinetics and Tolerability of a Single Oral Dose of Bendavia (MTP-131)

NCT01754818 | Completed Phase 1 DMC

• 1 other identifier: SPIO-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the study medication blood levels after administration of a single oral capsule of Bendavia at one of three dose levels. The effects of Bendavia on the volunteers will also be assessed.

Conditions

Healthy

Keywords

Pharmacokinetics; volunteers

Outcome Measures

Primary Outcomes (6)

• Mean peak plasma concentration (Cmax) of Bendavia (ng/ml) in each cohort.

  Blood drawn at pre-dose (immediately prior to study drug ingestion), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose will be assessed for Bendavia plasma concentrations. Mean Cmax is defined as the mean of maximum concentration reported for each subject by cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

• Mean Area Under the Curve (AUC) for Bendavia (hr.ng/ml) in the time from dosing to final plasma sample in each cohort.

  Blood drawn at pre-dose (immediately prior to study drug ingestion), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose will be assessed for Bendavia plasma concentrations. AUC (0-last) will be calculated using validated pharmacokinetic analysis software and mean AUC for Bendavia is defined as the mean of AUC (0-last) reported for each subject by cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

• Mean Time post-dose of the peak plasma concentration (Tmax) of Bendavia (hours) in each cohort.

  Blood drawn at pre-dose (immediately prior to study drug ingestion), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose will be assessed for Bendavia plasma concentrations. Mean Tmax is defined as the mean of time to reach maximum plasma concentration reported for each subject by cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

• Mean apparent clearance (CL/F) of Bendavia (ml/hr/kg) in each cohort.

  Blood drawn at pre-dose (immediately prior to study drug ingestion), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose will be assessed for Bendavia plasma concentrations. CL/F will be calculated using validated pharmacokinetic analysis software and mean CL/F for Bendavia is defined as the mean of CL/F reported for each subject by cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

• Mean Volume of Distribution (Vd/F) of Bendavia (ml/kg) in each cohort.

  Blood drawn at pre-dose (immediately prior to study drug ingestion), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose will be assessed for Bendavia plasma concentrations. Vd/F will be calculated using validated pharmacokinetic analysis software and mean Vd/F for Bendavia is defined as the mean of Vd/F reported for each subject by cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

• Mean Half Life(t1/2) of Bendavia (hours) in each cohort.

  Blood drawn at pre-dose (immediately prior to study drug ingestion), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose will be assessed for Bendavia plasma concentrations. t1/2 will be calculated using validated pharmacokinetic analysis software and mean t1/2 for Bendavia is defined as the mean of t1/2 reported for each subject by cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

Secondary Outcomes (6)

• Mean Area Under the Curve (AUC) for Bendavia metabolite M1 (hr.ng/ml) in the time from dosing to final plasma sample in each cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

• Mean Area Under the Curve (AUC) for Bendavia metabolite M2 (hr.ng/ml) in the time from dosing to final plasma sample in each cohort.

  Immediately prior to dosing (0hr) to 48 hours post-dose

• Mean change in concentration of urinary 8-isoprostane (pg/mg creatinine) from pre-dose through to 48 hours post-dose for each cohort.

  Prior to dosing (0hr) to 48 hours post-dose

• Mean change in concentration of urinary 8-hydroxy-2-deoxyguanosine (ng/mg creatinine) from pre-dose through to 48 hours post-dose for each cohort.

  Prior to dosing (0hr) to 48 hours post-dose

• Number of adverse events observed with and without Bendavia

  From time of study drug administration to End of Study (Day 3)

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo, oral capsule, no active study drug, single dose

Drug: Placebo

Bendavia 10mg

EXPERIMENTAL

Bendavia, oral capsule, 10mg, single dose

Drug: Bendavia 10mg; Drug: Placebo

Bendavia 50mg

EXPERIMENTAL

Bendavia, oral capsule, 50mg, single dose

Drug: Bendavia 50mg; Drug: Placebo

Bendavia 100mg

EXPERIMENTAL

Bendavia, oral capsule, 100mg, single dose

Drug: Bendavia 100mg; Drug: Placebo

Interventions

Bendavia 10mg DRUG

Bendavia 10mg

Bendavia 50mg DRUG

Bendavia 50mg

Bendavia 100mg DRUG

Bendavia 100mg

Placebo DRUG

Bendavia 100mg; Bendavia 10mg; Bendavia 50mg; 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 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 the study qualification visit,
• Clinically significant laboratory abnormalities as determined by the Principal Investigator at laboratory screening
• Creatinine clearance calculated by the Cockcroft and Gault method calculated to be \<90 mL/min for males and \<80 mL/min for females
• Clinically significant abnormalities on physical examination,
• Body weight less than 60 or greater than 80 kg and a body mass index 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,
• Participant in any research involving investigational product within 30 days before planned date of drug administration,
• Positive serology for human immunodeficiency virus type 1 or 2, hepatitis B surface antigen, or hepatitis C,
• Fever greater than 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,
• Women who are pregnant or breastfeeding,
• Employee or family member of the investigational site,

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (1)

Clinical Pharmacology of Miami

Miami, Florida, 33014, 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 BioTherapeutics Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: December 21, 2012
• Study Start: November 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: February 1, 2013
• Last Updated: February 6, 2013

Record last verified: 2013-02

Locations

US (1)