Safety and Pharmacokinetic (PK) Study of Oral Bendavia Administered for 7 Days

NCT01786915 | Completed Phase 1

• 1 other identifier: SPIO-102
• 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 repeat oral capsules (one capsule each day for seven days) of Bendavia at one of two dose levels. The effects of Bendavia on the volunteers will also be assessed.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (8)

• Mean peak plasma concentration (Cmax) of Bendavia (ng/ml) on Day 1 in each cohort.

  Blood drawn at pre-dose (immediately prior to study drug ingestion) and post-dose at +0.5, +1, +1.5, +2, +2.5, +3, +3.5, +4, +5, +6, +8, +12, +18 hours and pre-Day2-dose (approximately 24 hours post-Day1-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 (Day 1, 0hr) to 24 hours post-dose

• Mean peak plasma concentration (Cmax) of Bendavia (ng/ml) on Day 7 in each cohort.

  Blood drawn at Day 7 pre-dose (immediately prior to study drug ingestion) and post-dose at +0.5, +1, +1.5, +2, +2.5, +3, +3.5, +4, +5, +6, +8, +12, +18 and +24 hours 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 (Day 7, 0hr) to 24 hours post-dose

• Mean time to peak plasma concentration (Tmax) of Bendavia (hr) on Day 1 in each cohort.

  Blood drawn at Day 1 pre-dose (immediately prior to study drug ingestion) and post-dose at +0.5, +1, +1.5, +2, +2.5, +3, +3.5, +4, +5, +6, +8, +12, +18 hours and pre-Day2-dose (approximately 24 hours post-Day1-dose) will be assessed for Bendavia plasma concentrations. Mean Tmax is defined as the mean of the time of maximum concentration reported for each subject by cohort.

  Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose

• Mean time to peak plasma concentration (Tmax) of Bendavia (hr) on Day 7 in each cohort.

  Blood drawn at Day 7 pre-dose (immediately prior to study drug ingestion) and post-dose at +0.5, +1, +1.5, +2, +2.5, +3, +3.5, +4, +5, +6, +8, +12, +18 and +24 hours will be assessed for Bendavia plasma concentrations. Mean Tmax is defined as the mean of the time of maximum concentration reported for each subject by cohort.

  Immediately prior to dosing (Day 7, 0hr) to 24 hours post-dose

• Mean Area Under the Curve (AUC) from 0-24 hours on Day 1 for Bendavia (hr.ng/ml) in the time from dosing to 24 hours post-dose in each cohort.

  Blood drawn at Day 1 pre-dose (immediately prior to study drug ingestion) and post-dose at +0.5, +1, +1.5, +2, +2.5, +3, +3.5, +4, +5, +6, +8, +12 and +18 hours and pre-D2-dose (approximately 24 hours post-D1-dose) will be assessed for Bendavia plasma concentrations. AUC (0-24hr) will be calculated using validated pharmacokinetic analysis software and mean AUC for Bendavia is defined as the mean of AUC (0-24hr) reported for each subject by cohort

  Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose

• Mean Area Under the Curve (AUC) from 0-24 hours on Day 7 for Bendavia (hr.ng/ml) in the time from dosing to 24 hours post-dose in each cohort.

  Blood drawn at Day 7 pre-dose (immediately prior to study drug ingestion) and post-dose at +0.5, +1, +1.5, +2, +2.5, +3, +3.5, +4, +5, +6, +8, +12, +18 and +24 hours post-D7-dose will be assessed for Bendavia plasma concentrations. AUC (0-24hr) will be calculated using validated pharmacokinetic analysis software and mean AUC for Bendavia is defined as the mean of AUC (0-24hr) reported for each subject by cohort.

  Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose

• Ratio of AUC0-24h calculated on Day 7 to AUC0-24h calculated on Day 1 [AUC0-24h (d7)/AUC0-24h (d1)].

  Mean AUC (0-24hr) calculated at Day 7 as the ratio of Mean AUC (0-24hr) calculated at Day 1 will be calculated for each Bendavia-treated cohort.

  Immediately prior to dosing (Day 1, 0hr) to 24 hours post-Day 7-dose

• Number of adverse events observed with and without Bendavia

  Adverse events will be tabulated by treatment group. No statistical analysis will be performed.

  From time of study drug administration to End of Study (Day 10)

Secondary Outcomes (8)

• Mean change in concentration of urinary 8-isoprostane (pg/mg creatinine) from pre-dose through to study Day 10 for each cohort.

  Prior to dosing (Day 1, 0hr) to Study Day 10

• Mean change in concentration of urinary 8-hydroxy-2-deoxyguanosine (ng/mg creatinine) from pre-dose through to study Day 10 for each cohort.

  Prior to dosing (Day 1, 0hr) to Study Day 10

• Mean Area Under the Curve (AUC0-24hr) on Day 1 for Bendavia metabolite M1 (hr.ng/ml) in the time from dosing to 24 hours post-D1-dose in each cohort.

  Immediately prior to dosing (Day 1,0hr) to 24 hours post-D1-dose

• Mean Area Under the Curve (AUC0-24hr) on Day 1 for Bendavia metabolite M2 (hr.ng/ml) in the time from dosing to 24 hours post-D1-dose in each cohort.

  Immediately prior to dosing (Day 1,0hr) to 24 hours post-D1-dose

• Mean Area Under the Curve on Day 7 (AUC0-24hr) for Bendavia metabolite M1 (hr.ng/ml) in the time from dosing to 24 hours post-D7-dose in each cohort.

  Immediately prior to dosing (Day 7,0hr) to 24 hours post-D7-dose

Study Arms (3)

Bendavia 10mg

EXPERIMENTAL

Bendavia capsule, 10mg, once daily for 7 days

Drug: Bendavia 10mg; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo (matching), once daily for 7 days

Drug: Placebo

Bendavia 50mg

EXPERIMENTAL

Bendavia capsule, 50mg, once daily for 7 days

Drug: Bendavia 50mg; Drug: Placebo

Interventions

Bendavia 10mg DRUG

Also known as: MTP-131

Bendavia 10mg

Bendavia 50mg DRUG

Also known as: MTP-131

Bendavia 50mg

Placebo DRUG

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 interuterine 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 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 kg or greater than 80 kg or 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 HIV 1, HIV 2, HBsAg, or hepatitis C virus (HCV),
• 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 an employee of the investigational site,

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (1)

Clinical Pharmacology of Miami Inc

Miami, Florida, 33014, United States

Location

MeSH Terms

Interventions

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

Study Officials

• Richard Straube, MD

  Stealth BioTherapeutics Inc.

  STUDY DIRECTOR

• Kenneth C Lasseter, MD

  Climincal Pharmacology of Miami Inc

  PRINCIPAL INVESTIGATOR

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: February 6, 2013
• First Posted: February 8, 2013
• Study Start: February 1, 2013
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 2, 2014

Record last verified: 2014-03

Locations

US (1)