Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Tolerability, and Pharmacokinetics of a Single Oral Dose of SKI-O-703 in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02717988
Recruitment Status : Completed
First Posted : March 24, 2016
Last Update Posted : February 28, 2018
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
Oscotec Inc.

Brief Summary:
This double-blind, placebo-controlled, single ascending dose study is designed to demonstrate safety, tolerability and pharmacokinetics of SKI-O-703 in healthy volunteers. The results of this study will guide selection of dose levels for future multiple dose studies in healthy volunteers and adult patients with moderately to severely active rheumatoid arthritis.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: SKI-O-703 capsule Drug: Placebo capsule Phase 1

Detailed Description:
This is a double-blind, placebo-controlled study in healthy adult volunteers that will be conducted to evaluate the safety, tolerability, and pharmacokinetics of ascending single doses of SKI-O-703. A total of 48 subjects are planned to participate in 6 cohorts (8 subjects each). In each cohort, 6 subjects will be randomly assigned to receive SKI-O-703 and 2 subjects will be randomly assigned to matching placebo. Dosing will be initiated in the 50 mg dose cohort and sequentially escalated to the 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg cohorts.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: A Phase 1, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of a Single Oral Dose of SKI-O-703 in Healthy Volunteers
Actual Study Start Date : September 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SKI-O-703 50 mg
SKI-O-703 capsule (2x25 mg)
Drug: SKI-O-703 capsule
SKI-O-703 25 mg capsule or 200 mg capsule without excipient

Experimental: SKI-O-703 100 mg
SKI-O-703 capsule (4x25 mg)
Drug: SKI-O-703 capsule
SKI-O-703 25 mg capsule or 200 mg capsule without excipient

Experimental: SKI-O-703 200 mg
SKI-O-703 capsule (1x200 mg)
Drug: SKI-O-703 capsule
SKI-O-703 25 mg capsule or 200 mg capsule without excipient

Experimental: SKI-O-703 400 mg
SKI-O-703 capsule (2x200 mg)
Drug: SKI-O-703 capsule
SKI-O-703 25 mg capsule or 200 mg capsule without excipient

Experimental: SKI-O-703 600 mg
SKI-O-703 capsule (3x200 mg)
Drug: SKI-O-703 capsule
SKI-O-703 25 mg capsule or 200 mg capsule without excipient

Experimental: SKI-O-703 800 mg
SKI-O-703 capsule (4x200 mg)
Drug: SKI-O-703 capsule
SKI-O-703 25 mg capsule or 200 mg capsule without excipient

Placebo Comparator: Placebo
Placebo capsule
Drug: Placebo capsule
Placebo 180 mg capsule filled with microcrystalline cellulose




Primary Outcome Measures :
  1. Number of participants (Healthy Volunteers) with reported adverse events receiving single dose of SKI-O-703 as assessment of safety and tolerability. [ Time Frame: 28 days ]
    Safety and tolerability of SKI-O-703 as measured by subject incidence of treatment-related Adverse Events.


Secondary Outcome Measures :
  1. Area under the concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-t) for estimating the pharmacokinetic parameters of SKI-O-592 (the free base of SKI-O-703) and its metabolites. [ Time Frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    AUC0-t will be reported

  2. Area under the concentration versus time curve from time 0 extrapolated to infinity (AUC0-inf) [ Time Frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    AUC0-inf will be reported

  3. Maximum observed plasma concentration (Cmax) [ Time Frame: Days 0 (pre-dose), 1 (dosing), and post-dose at days 2, 3 and 4 ]
    Cmax will be reported

  4. Time to reach the maximum observed plasma concentration (Tmax) [ Time Frame: Day 0 (pre-dose), Day1 (dosing), and post-dose at days 2, 3 and 4 ]
    Tmax will be reported

  5. Apparent terminal elimination half-life (T1/2) [ Time Frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    T1/2 will be reported

  6. Apparent volume of distribution (Vd/F) (SKI-O-592, free base of SKI-O-703) [ Time Frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    Vd/F will be reported

  7. Apparent oral clearance (CL/F) (SKI-O-592 only) [ Time Frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    CL/F will be reported.

  8. Terminal elimination rate constant (Kel) [ Time Frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    Kel will be reported.

  9. Mean residence time (MRT) [ Time Frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    MRT will be reported.

  10. Metabolite ratio (Rmet), calculated as AUC0-t (metabolite) / AUC0-t (parent) (metabolites M1, M2 and M4 only). [ Time Frame: Day 0 (pre-dose), Day 1 (dosing) and post-dose at Days 2, 3 and 4 ]
    Rmet will be reported.

  11. Renal clearance (SKI-O-592, free base of SKI-O-703 only) [ Time Frame: Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    Renal clearance will be reported.

  12. Amount of drug excreted in urine over the collection intervals of 0 to 4 hours (Ae0-4), 4 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 48 hours, and 48 to 72 hours post dose. [ Time Frame: Day 1 (dosing), and post-dose at days 2, 3 and 4 ]
    Ae will be reported


Other Outcome Measures:
  1. The pharmacodynamics variable will be the change in the percentage of activated gp53/CD63+ basophils and will be evaluated from serial blood samples collected from subjects who have received SKI-O-703 or placebo. [ Time Frame: Pre-dose, Day 1(dosing) and post-dose at Day 2 ]
    changes in the percentage of activated gp53/CD63+ basophils will be reported



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Willing and able to provide written informed consent for participation prior to completing any study procedures
  • Considered by the investigator to be in good health as determined by the absence of clinically significant diseases or clinically significant abnormal values as determined by a detailed medical history review, complete physical examination, and clinical laboratory assessments. Clinical significance for any out-of-range laboratory test results will be determined by the principal investigator
  • Male subjects and female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive
  • Female subjects of non-childbearing potential are those who are surgically sterile at least 6 months or postmenopausal at least 2 years and have follicle-stimulating hormone serum levels consistent with postmenopausal status.
  • Male subjects must agree to use a condom with spermicide or abstain from sexual intercourse for 90 days after dosing
  • Male subjects must agree not to donate sperm for 90 days after dosing
  • Female subjects must have negative serum pregnancy test results at Screening and Day -1
  • Subject must have a body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, and weight ≥50 kg
  • Subject must be able to understand the study and any risks to participation and able to communicate with the investigator

Exclusion Criteria:

  • History of any clinically significant disease or disorder that may put the subject at risk if he/she participates in the study, might affect the subject's ability to participate in the study, or influence the study results
  • History or presence of any gastrointestinal, hepatic or renal disease, or any other condition known to interfere with the absorption, distribution, metabolism, or excretion (ADME) of drugs
  • Any surgical or medical conditions possibly affecting drug ADME (eg, bariatric procedure)
  • Any medical/surgical procedure or trauma within 4 weeks of Day -1 as determined by the investigator
  • Any clinically significant infection within 3 months of Day -1 as determined by the investigator
  • Any of the following abnormal laboratory values upon repeat testing at Screening or check-in:

    • Hemoglobin <the lower limit of normal (LLN)
    • Platelet count <LLN
    • Absolute neutrophil count <LLN or >the upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >ULN
    • Creatinine or blood urea nitrogen >ULN
    • Other clinically significant abnormal laboratory results in the opinion of the investigator
  • Use of concomitant medications from 30 days or 5 half-lives prior to Day -1 (whichever is longer), including prescription medications, nutritional supplements, herbal remedies, and over-the-counter medications
  • Receipt of any investigational medication within 30 days or 5 half-lives prior to Day -1, whichever is longer
  • Use of tobacco or nicotine-containing products within 30 days prior to Day -1 and through the End-of-Study visit
  • Use of cytochrome P450 3A isozyme (CYP3A) inducers and inhibitors (including St. John's wort) within 30 days of dosing
  • Food or beverage containing alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, mustard), and charbroiled meats within 1 week prior to dosing
  • History of substance abuse, drug addiction, or alcoholism
  • Positive urine drug or urine alcohol test result at screening or Day -1 or unable to abstain from alcohol from 72 hours prior to study entry to the End-of-Study visit
  • Unable to abstain from caffeine and xanthine-containing products from 72 hours prior to dosing through discharge from the study site
  • Female subjects who are pregnant or lactating or have a positive serum pregnancy test result at Screening
  • Positive test results at Screening for human immunodeficiency virus, hepatitis B surface antigen (HBsAg), hepatitis C virus antibody, or hepatitis B core antibody and negative for HBsAg
  • Recent (past 5 years) history of malignancy except successfully treated basal cell carcinoma
  • High blood pressure, defined as >140 millimeters of mercury (mm Hg) systolic blood pressure or >90 mm Hg diastolic blood pressure upon repeat confirmation
  • Cardiac arrhythmias or clinically significant ECG findings upon repeat confirmation by the investigator
  • Corrected QT interval (QTc) >450 milliseconds or deemed clinically significant by the investigator
  • Family history of long QT syndrome
  • Blood loss or blood donation >450 mL within 4 weeks of study drug dosing
  • History of sensitivity to drugs with chemical similarity to the study drug, its components, or excipients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02717988


Locations
Layout table for location information
United States, Texas
PPD Development, LP
Austin, Texas, United States, 78744
Sponsors and Collaborators
Oscotec Inc.
PPD
Layout table for additonal information
Responsible Party: Oscotec Inc.
ClinicalTrials.gov Identifier: NCT02717988    
Other Study ID Numbers: OSCO-P1201
First Posted: March 24, 2016    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: October 2017
Keywords provided by Oscotec Inc.:
rheumatoid arthritis
healthy volunteers
moderately to severely active
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases