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Safety, Tolerability and Pharmacokinetics of SP-8203

Primary Purpose

Ischemic Stroke

Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
SP-8203
Placebo
Sponsored by
Shin Poong Pharmaceutical Co. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring acute ischemic stroke, ischemic stroke, stroke

Eligibility Criteria

20 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Male or female ages of 20 and 45 years, inclusive.
  2. Females must be non-pregnant, non-lactating, and practicing an acceptable method of birth control, or be surgically sterile or post-menopausal.
  3. Males must be agree to practice an medically acceptable method of birth control and will not donate sperm during the study.
  4. Subject's body mass index (BMI) is ≥ 18 and ≤ 32, inclusive.
  5. Subject does not smoke and has not smoked or used nicotine-containing products for at least 6 continuous months prior to the first dose.
  6. Subject has adequate venous access for repeated venipuncture.
  7. Subject has hemoglobin >/= 11.5 g/dL.
  8. Subject agrees to abstain from taking any dietary supplements or non-prescription drugs (except for multivitamins or as otherwise authorized by the Investigator and Medical Monitor) for 14 days prior to CRU admission through discharge.
  9. Subject agrees to abstain from consuming alcohol-containing beverages for 3 days prior to CRU admission through discharge.
  10. Subject agrees to abstain from consuming caffeine- or chocolate-containing products from CRU admission through discharge.
  11. Subject is in general good health based on medical history and clinically acceptable results on the following assessments: physical examination, vital signs, 12 lead ECG, clinical chemistry, hematology/coagulation, and urinalysis.
  12. Seated systolic blood pressure must be >90 mmHg and >140 mmHg and seated diastolic blood pressure must be >50 mmHg and >90 mmHg at Screening and Baseline.
  13. Subject voluntarily provides written informed consent.

Exclusion Criteria:

  1. Subject has a history or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
  2. History of anaphylaxis, a documented hypersensitivity reaction, or a clinically important idiosyncratic reaction to any drug.
  3. Predisposing condition that could interfere with the distribution, metabolism, or excretion of drugs or any condition that may confound the PK analyses.
  4. Positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C virus.
  5. Have chronic Qt prolongation syndrome (i.e. Qt > 450 ms for males and >470 ms for females) in repeated EKG measurements.
  6. Drugs or substances known to inhibit or induce cytochrome 2D6 (CYP) enzymes within 28 days prior to the first dose and throughout the study.
  7. Recent (2-year) history or evidence of alcoholism or drug abuse.
  8. Positive for alcohol or drugs of abuse at the Screening Visit or upon admission to the CRU.
  9. Special diet during the 28 days prior to the first dose (eg, Atkins, South Beach, or any other high protein / high fat diets).
  10. Subject reports difficulty fasting or consuming standardized meals.
  11. Subject has donated blood or plasma (eg. Plasmapheresis) within 28 days prior to the first dose of study medication.
  12. Participated in another clinical trial within 90 days prior to dosing.
  13. History of malignancy within the past 5 years, with the exception of successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix.
  14. Investigator's decision to exclude for other reason.

Sites / Locations

  • Asan Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SP-8203

Placebo

Arm Description

Active arm

Matching Placebo

Outcomes

Primary Outcome Measures

The incidence rate of adverse events, and adverse drug reaction in single ascending doses (SAD)
The safety of SP-8203 will be evaluated by monitoring treatment-emergent adverse events (AE), changes in 12 lead electrocardiograms (ECG), clinical laboratory tests, vital signs, and physical examinations, as well as clinically important changes in heart rate.
The incidence rate of adverse events, and adverse drug reaction in multiple ascending doses (MAD)
The safety of SP-8203 will be evaluated by monitoring treatment-emergent adverse events (AE), changes in 12 lead electrocardiograms (ECG), clinical laboratory tests, vital signs, and physical examinations, as well as clinically important changes in heart rate.
Pharmacokinetics in single ascending doses (SAD)
Plasma concentrations of SP-8203 will be measured by a validated liquid chromatography-tandem mass spectrometry assay procedure and PK parameters will be determined. Urine will be collected predose and at specified intervals postdose for the determination of SP-8203 renal clearance.
Pharmacokinetics in multiple ascending doses (MAD)
Plasma concentrations of SP-8203 will be measured by a validated liquid chromatography-tandem mass spectrometry assay procedure and PK parameters will be determined. Urine will be collected predose and at specified intervals postdose for the determination of SP-8203 renal clearance.

Secondary Outcome Measures

Full Information

First Posted
December 21, 2012
Last Updated
July 20, 2020
Sponsor
Shin Poong Pharmaceutical Co. Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT01757795
Brief Title
Safety, Tolerability and Pharmacokinetics of SP-8203
Official Title
A Phase I Single-Center, Randomized, Double-Blind, Placebo-Controlled Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses and Multiple Doses of SP-8203
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
December 23, 2013 (Actual)
Primary Completion Date
March 11, 2015 (Actual)
Study Completion Date
March 11, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shin Poong Pharmaceutical Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Phase I study in health volunteers to assess the safety, tolerability and pharmacokinetics of escalating single doses and multiple doses of SP-8203
Detailed Description
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, 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
acute ischemic stroke, ischemic stroke, stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SP-8203
Arm Type
Experimental
Arm Description
Active arm
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo
Intervention Type
Drug
Intervention Name(s)
SP-8203
Other Intervention Name(s)
SP8203HCL
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be intravenously administered
Primary Outcome Measure Information:
Title
The incidence rate of adverse events, and adverse drug reaction in single ascending doses (SAD)
Description
The safety of SP-8203 will be evaluated by monitoring treatment-emergent adverse events (AE), changes in 12 lead electrocardiograms (ECG), clinical laboratory tests, vital signs, and physical examinations, as well as clinically important changes in heart rate.
Time Frame
Follow-up to 7 days after administration
Title
The incidence rate of adverse events, and adverse drug reaction in multiple ascending doses (MAD)
Description
The safety of SP-8203 will be evaluated by monitoring treatment-emergent adverse events (AE), changes in 12 lead electrocardiograms (ECG), clinical laboratory tests, vital signs, and physical examinations, as well as clinically important changes in heart rate.
Time Frame
Follow-up to 13 days after first administration
Title
Pharmacokinetics in single ascending doses (SAD)
Description
Plasma concentrations of SP-8203 will be measured by a validated liquid chromatography-tandem mass spectrometry assay procedure and PK parameters will be determined. Urine will be collected predose and at specified intervals postdose for the determination of SP-8203 renal clearance.
Time Frame
within 3 days of administration
Title
Pharmacokinetics in multiple ascending doses (MAD)
Description
Plasma concentrations of SP-8203 will be measured by a validated liquid chromatography-tandem mass spectrometry assay procedure and PK parameters will be determined. Urine will be collected predose and at specified intervals postdose for the determination of SP-8203 renal clearance.
Time Frame
within 9 days of first administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female ages of 20 and 45 years, inclusive. Females must be non-pregnant, non-lactating, and practicing an acceptable method of birth control, or be surgically sterile or post-menopausal. Males must be agree to practice an medically acceptable method of birth control and will not donate sperm during the study. Subject's body mass index (BMI) is ≥ 18 and ≤ 32, inclusive. Subject does not smoke and has not smoked or used nicotine-containing products for at least 6 continuous months prior to the first dose. Subject has adequate venous access for repeated venipuncture. Subject has hemoglobin >/= 11.5 g/dL. Subject agrees to abstain from taking any dietary supplements or non-prescription drugs (except for multivitamins or as otherwise authorized by the Investigator and Medical Monitor) for 14 days prior to CRU admission through discharge. Subject agrees to abstain from consuming alcohol-containing beverages for 3 days prior to CRU admission through discharge. Subject agrees to abstain from consuming caffeine- or chocolate-containing products from CRU admission through discharge. Subject is in general good health based on medical history and clinically acceptable results on the following assessments: physical examination, vital signs, 12 lead ECG, clinical chemistry, hematology/coagulation, and urinalysis. Seated systolic blood pressure must be >90 mmHg and >140 mmHg and seated diastolic blood pressure must be >50 mmHg and >90 mmHg at Screening and Baseline. Subject voluntarily provides written informed consent. Exclusion Criteria: Subject has a history or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease. History of anaphylaxis, a documented hypersensitivity reaction, or a clinically important idiosyncratic reaction to any drug. Predisposing condition that could interfere with the distribution, metabolism, or excretion of drugs or any condition that may confound the PK analyses. Positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C virus. Have chronic Qt prolongation syndrome (i.e. Qt > 450 ms for males and >470 ms for females) in repeated EKG measurements. Drugs or substances known to inhibit or induce cytochrome 2D6 (CYP) enzymes within 28 days prior to the first dose and throughout the study. Recent (2-year) history or evidence of alcoholism or drug abuse. Positive for alcohol or drugs of abuse at the Screening Visit or upon admission to the CRU. Special diet during the 28 days prior to the first dose (eg, Atkins, South Beach, or any other high protein / high fat diets). Subject reports difficulty fasting or consuming standardized meals. Subject has donated blood or plasma (eg. Plasmapheresis) within 28 days prior to the first dose of study medication. Participated in another clinical trial within 90 days prior to dosing. History of malignancy within the past 5 years, with the exception of successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix. Investigator's decision to exclude for other reason.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyun-Seop Bae, MD, Ph.D.
Organizational Affiliation
ASAN Medical Center Songpa-gu, Seoul, Korea, Republic of
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of

12. IPD Sharing Statement

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Safety, Tolerability and Pharmacokinetics of SP-8203

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