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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo, oral capsule, no active study drug, single dose |
|
| Bendavia 10mg | Experimental | Bendavia, oral capsule, 10mg, single dose |
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| Bendavia 50mg | Experimental | Bendavia, oral capsule, 50mg, single dose |
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| Bendavia 100mg | Experimental | Bendavia, oral capsule, 100mg, single dose |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bendavia 10mg | Drug |
| ||
| Bendavia 50mg |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 metabolite M1 plasma concentrations. AUC (0-last) will be calculated using validated pharmacokinetic analysis software and mean AUC for Bendavia metabolite M1 is defined as the mean of AUC (0-last) reported for each subject by cohort. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kenneth C Lasseter, MD | Clinical Pharmacology of Miami | Principal Investigator |
| Richard Straube, MD | Stealth BioTherapeutics Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami | Miami | Florida | 33014 | United States |
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| ID | Term |
|---|---|
| C506540 | arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide |
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|
| Bendavia 100mg | Drug |
|
| Placebo | Drug |
|
| 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 |
| 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. | 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 metabolite M2 plasma concentrations. AUC (0-last) will be calculated using validated pharmacokinetic analysis software and mean AUC for Bendavia metabolite M2 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 change in concentration of urinary 8-isoprostane (pg/mg creatinine) from pre-dose through to 48 hours post-dose for each cohort. | Spot urine samples will be collected at pre-dose, 12, 24 and 48 hours post-dose for assay of 8-isoprostane (8-EPIPGF2a) and creatinine. Change from baseline value at each time point assessed will be calculated for each subject. Mean change from baseline is defined as the mean of the change in 8-EPIPGF2a/creatinine for each subject by 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. | Spot urine samples will be collected at pre-dose, 12, 24 and 48 hours post-dose for assay of 8- hydroxy-2-deoxyguanosine (8-OHDG) and creatinine. Change from baseline value at each time point assessed will be calculated for each subject. Mean change from baseline is defined as the mean of the change in 8-OHDG/creatinine for each subject by cohort. | Prior to dosing (0hr) to 48 hours post-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 3) |
| Mean change from baseline in High Sensitivity C-Reactive Protein (hs-CRP; ng/L) through 48 hours post-dose. | hs-CRP will be evaluated prior to (Baseline) and after (12, 24 and 48 hours) study drug administration. Change from baseline value at each time point assessed will be calculated for each subject. Mean change from baseline is defined as the mean of the change in hs-CRP for each subject by cohort. | Pre-dose to 48 hours post-dose |