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

NCT02717988 | Completed Phase 1

• 1 other identifier: OSCO-P1201
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; healthy volunteers; moderately to severely active

Outcome Measures

Primary Outcomes (1)

• Number of participants (Healthy Volunteers) with reported adverse events receiving single dose of SKI-O-703 as assessment of safety and tolerability.

  Safety and tolerability of SKI-O-703 as measured by subject incidence of treatment-related Adverse Events.

  28 days

Secondary Outcomes (12)

• 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.

  Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4

• Area under the concentration versus time curve from time 0 extrapolated to infinity (AUC0-inf)

  Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4

• Maximum observed plasma concentration (Cmax)

  Days 0 (pre-dose), 1 (dosing), and post-dose at days 2, 3 and 4

• Time to reach the maximum observed plasma concentration (Tmax)

  Day 0 (pre-dose), Day1 (dosing), and post-dose at days 2, 3 and 4

• Apparent terminal elimination half-life (T1/2)

  Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4

Other Outcomes (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.

  Pre-dose, Day 1(dosing) and post-dose at Day 2

Study Arms (7)

SKI-O-703 50 mg

EXPERIMENTAL

SKI-O-703 capsule (2x25 mg)

Drug: SKI-O-703 capsule

SKI-O-703 100 mg

EXPERIMENTAL

SKI-O-703 capsule (4x25 mg)

Drug: SKI-O-703 capsule

SKI-O-703 200 mg

EXPERIMENTAL

SKI-O-703 capsule (1x200 mg)

Drug: SKI-O-703 capsule

SKI-O-703 400 mg

EXPERIMENTAL

SKI-O-703 capsule (2x200 mg)

Drug: SKI-O-703 capsule

SKI-O-703 600 mg

EXPERIMENTAL

SKI-O-703 capsule (3x200 mg)

Drug: SKI-O-703 capsule

SKI-O-703 800 mg

EXPERIMENTAL

SKI-O-703 capsule (4x200 mg)

Drug: SKI-O-703 capsule

Placebo

PLACEBO COMPARATOR

Placebo capsule

Drug: Placebo capsule

Interventions

SKI-O-703 capsule DRUG

SKI-O-703 25 mg capsule or 200 mg capsule without excipient

SKI-O-703 100 mg; SKI-O-703 200 mg; SKI-O-703 400 mg; SKI-O-703 50 mg; SKI-O-703 600 mg; SKI-O-703 800 mg

Placebo capsule DRUG

Placebo 180 mg capsule filled with microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oscotec Inc.: lead
• PPD Development, LP: collaborator

Study Sites (1)

PPD Development, LP

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

cevidoplenib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2016
• First Posted: March 24, 2016
• Study Start: September 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: February 28, 2018

Record last verified: 2017-10

Locations

US (1)