Phase 1 Randomized, Double-Blind, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Repeat Administration (7 Days) of Ascending Oral Doses of Bendavia in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Bendavia 10mg
- Conditions
- Healthy Volunteers
- Sponsor
- Stealth BioTherapeutics Inc.
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Number of adverse events observed with and without Bendavia
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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),
Arms & Interventions
Bendavia 10mg
Bendavia capsule, 10mg, once daily for 7 days
Intervention: Bendavia 10mg
Bendavia 10mg
Bendavia capsule, 10mg, once daily for 7 days
Intervention: Placebo
Placebo
Placebo (matching), once daily for 7 days
Intervention: Placebo
Bendavia 50mg
Bendavia capsule, 50mg, once daily for 7 days
Intervention: Bendavia 50mg
Bendavia 50mg
Bendavia capsule, 50mg, once daily for 7 days
Intervention: Placebo
Outcomes
Primary Outcomes
Number of adverse events observed with and without Bendavia
Time Frame: From time of study drug administration to End of Study (Day 10)
Adverse events will be tabulated by treatment group. No statistical analysis will be performed.
Mean peak plasma concentration (Cmax) of Bendavia (ng/ml) on Day 1 in each cohort.
Time Frame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
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.
Mean peak plasma concentration (Cmax) of Bendavia (ng/ml) on Day 7 in each cohort.
Time Frame: Immediately prior to dosing (Day 7, 0hr) to 24 hours post-dose
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.
Mean time to peak plasma concentration (Tmax) of Bendavia (hr) on Day 1 in each cohort.
Time Frame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
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.
Mean time to peak plasma concentration (Tmax) of Bendavia (hr) on Day 7 in each cohort.
Time Frame: Immediately prior to dosing (Day 7, 0hr) to 24 hours post-dose
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.
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.
Time Frame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
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
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.
Time Frame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
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.
Ratio of AUC0-24h calculated on Day 7 to AUC0-24h calculated on Day 1 [AUC0-24h (d7)/AUC0-24h (d1)].
Time Frame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-Day 7-dose
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.
Secondary Outcomes
- 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)
- Mean Area Under the Curve on Day 7 (AUC0-24hr) for Bendavia metabolite M2 (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)
- Ratio of AUC0-24h for M1 calculated on Day 7 to AUC0-24h calculated on Day 1 [AUC0-24h (d7)/AUC0-24h (d1)].(Immediately prior to dosing (Day 1, 0hr) to 24 hours post-Day 7-dose)
- Ratio of AUC0-24h for M2 calculated on Day 7 to AUC0-24h calculated on Day 1 [AUC0-24h (d7)/AUC0-24h (d1)].(Immediately prior to dosing (Day 1, 0hr) to 24 hours post-Day 7-dose)