Clinical trial NCT01786915: Safety and Pharmacokinetic (PK) Study of Oral Bendavia Administered for 7 Days
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2013-02-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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),
* 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,
* Subjects who currently smoke cigarettes, cigars, pipes or chew tobacco products or who have used any tobacco product in the 30 days prior to screening,
* Subjects who are either unwilling to agree to refrain from use or found to be using:

  * Alcohol, caffeine, xanthine-containing food or beverages, nicotine products and over-the-counter medications with the exception of Tylenol from 24 hours prior to dosing and throughout the confinement periods
  * Prescription medications from 14 days prior to and 7 days post treatment (excluding hormonal contraceptives)
  * Hormonal contraceptives without concomitant use of double-barrier contraceptives (condom, diaphragm with spermicide) for a period of 7 days prior to and 30 days post treatment
* Subjects having previous exposure to Bendavia

Primary outcomes:
measure: Mean peak plasma concentration (Cmax) of Bendavia (ng/ml) on Day 1 in each cohort.
timeFrame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
measure: Mean peak plasma concentration (Cmax) of Bendavia (ng/ml) on Day 7 in each cohort.
timeFrame: Immediately prior to dosing (Day 7, 0hr) to 24 hours post-dose
measure: Mean time to peak plasma concentration (Tmax) of Bendavia (hr) on Day 1 in each cohort.
timeFrame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
measure: Mean time to peak plasma concentration (Tmax) of Bendavia (hr) on Day 7 in each cohort.
timeFrame: Immediately prior to dosing (Day 7, 0hr) to 24 hours post-dose
measure: 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.
timeFrame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
measure: 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.
timeFrame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-dose
measure: Ratio of AUC0-24h calculated on Day 7 to AUC0-24h calculated on Day 1 [AUC0-24h (d7)/AUC0-24h (d1)].
timeFrame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-Day 7-dose
measure: Number of adverse events observed with and without Bendavia
timeFrame: From time of study drug administration to End of Study (Day 10)
Secondary outcomes:
measure: Mean change in concentration of urinary 8-isoprostane (pg/mg creatinine) from pre-dose through to study Day 10 for each cohort.
timeFrame: Prior to dosing (Day 1, 0hr) to Study Day 10
measure: Mean change in concentration of urinary 8-hydroxy-2-deoxyguanosine (ng/mg creatinine) from pre-dose through to study Day 10 for each cohort.
timeFrame: Prior to dosing (Day 1, 0hr) to Study Day 10
measure: 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.
timeFrame: Immediately prior to dosing (Day 1,0hr) to 24 hours post-D1-dose
measure: 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.
timeFrame: Immediately prior to dosing (Day 1,0hr) to 24 hours post-D1-dose
measure: 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.
timeFrame: Immediately prior to dosing (Day 7,0hr) to 24 hours post-D7-dose
measure: 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.
timeFrame: Immediately prior to dosing (Day 7,0hr) to 24 hours post-D7-dose
measure: Ratio of AUC0-24h for M1 calculated on Day 7 to AUC0-24h calculated on Day 1 [AUC0-24h (d7)/AUC0-24h (d1)].
timeFrame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-Day 7-dose
measure: Ratio of AUC0-24h for M2 calculated on Day 7 to AUC0-24h calculated on Day 1 [AUC0-24h (d7)/AUC0-24h (d1)].
timeFrame: Immediately prior to dosing (Day 1, 0hr) to 24 hours post-Day 7-dose
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami Inc
state: Florida
Study officials:
affiliation: Stealth BioTherapeutics Inc.
name: Richard Straube, MD
role: STUDY_DIRECTOR
affiliation: Climincal Pharmacology of Miami Inc
name: Kenneth C Lasseter, MD
role: PRINCIPAL_INVESTIGATOR
References: