Phase I study in health volunteers to assess the safety, tolerability and pharmacokinetics of escalating single doses and multiple doses of SP-8203
This is a Phase I, single-center, randomized, double-blind, placebo-controlled study of the safety, tolerability, and PK of escalating single doses and multiple doses of SP 8203 in healthy adult male and female subjects.
In the SAD Part, the first cohort of 8 subjects will be randomly assigned to receive a single IV dose of either SP-8203 (n=6) or placebo (n=2). Following medical review of safety, PK, and biomarker data, subsequent cohorts of 8 new subjects will receive higher single doses of SP-8203 (6 subjects) or placebo (2 subjects). Dose escalation will continue until a single MTD of SP-8203 is identified. If a single-dose MTD is not defined within the projected dose range (see Section 4.1.3), additional cohorts of 8 subjects may be added to receive higher doses to achieve the objectives of the study. Alternate doses may be administered following medical review of the results of each cohort.
In the MAD Part of the study the first cohort of 8 subjects will receive a single dose of SP 8203 every day and 1 subject will receive a single dose of placebo every day for 7 consecutive days. Doses will be administered at the same time (± 15 minutes) every day. Following medical review of all safety and biomarker data, subsequent cohorts of 7 drug-naive subjects will receive higher single doses of SP-8203 (6 subjects) or placebo (2 subject) every day for 7 consecutive days (see Section 4.1.3). Study drug dose-escalation will continue until a multiple-dose MTD regimen of SP-8203 is identified. If a multiple-dose MTD is not defined within this range, additional cohorts of 8 subjects may be added to achieve the objectives of the study. Alternate doses and/or dosing regimens may be administered following medical review of the safety, biomarker, and PK results of the SAD Part, and prior cohorts in the MAD Part of the study.
The MTD will be defined as the highest dose that does not lead to unacceptable toxicity in one or more subjects based on the frequency, nature, and severity of AEs or other safety parameter abnormalities. The Investigator, Sponsor, and Medical Monitor will jointly assess the general safety and tolerability of each dose based on available data prior to escalating to the next higher dose. Successive higher doses will be administered only if previous doses are adequately tolerated. Intermediate doses may be tested, or a dose level may be repeated, as appropriate, depending on the safety profile observed.
Each subject will complete Screening, Baseline, Treatment, and Follow-Up Phases. The Screening Phase will be conducted on an outpatient basis within 30 days, but no sooner than 3 days, prior to the start of the Baseline Phase. The Baseline Phase will consist of admission to the CRU and final qualification assessments.
In the SAD Part, the Treatment Phase will consist of dosing (after which subjects will be considered enrolled in the study), postdose safety assessments, and blood and urine collection for the next 48 hours. Subjects will be discharged approximately 48 hours after study drug administration, provided all available assessments are clinically acceptable to the Investigator, and will return for follow-up assessments 2-4 days later. In the MAD Part, The Treatment Phase will last for 9 days following the first dose. Subjects will be dosed each morning for 7 consecutive days. Safety assessments will be made, and blood and urine will be collected prior to, and at prescribed intervals postdose, over the next 9 consecutive days. Subjects will be discharged approximately 48 hours following the last dose, and will return for follow-up assessments 2-4 days later.
Safety will be evaluated by physical examination, by evaluation of vital signs, 12 lead ECG, Holter monitoring, clinical laboratory blood and urine test results, and AE assessments. Blood samples for determining plasma concentrations of SP 8203 and its metabolites, assessments of Mn-SOD mRNA, and FRAP biomarkers will be obtained immediately prior to dosing and at prescribed intervals during the Treatment Phase. Urine samples will be collected predose and pooled urine samples will be collected postdose for determination of SP 8203 renal clearance and metabolites.
- Placebo Drug
ARM 1: Kind: Experimental Label: Placebo Description: Matching Placebo
- SP-8203 Drug
Other Names: SP-8203 is produced by Shin Poong Pharmaceutical company Intervention Desc: SP-8203 injection at single ascending doses of 10 mg, 20 mg, 40 mg, 80 mg, 160 mg and 240 mg (optional) SP-8203 injection at multiple ascending doses for 7 days at least 2 dose levels below the MTD in the single ascending portion of the trial ARM 1: Kind: Experimental Label: SP-8203 Description: Active arm
- Allocation: Randomized
- Masking: Double Blind (Subject, Investigator)
- Purpose: Treatment
- Endpoint: Safety Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||Efficacy||SAD - Days 1-5; MAD - Days 1-9||No|
|Primary||Safety||SAD - Days 1-5 and Mad - Days 1-9||Yes|
|Primary||Pharmacokinetics||SAD - Days 1-5 and MAD - Days 1-9||No|