Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SKI-O-703 in Healthy Volunteers

NCT03315494 | Completed Phase 1

• 1 other identifier: OSCO-P1202
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This double-blind, placebo-controlled, multiple ascending dose study is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of SKI-O-703 in healthy volunteers.

Conditions

Arthritis, Rheumatoid

Keywords

rheumatoid arthritis; healthy volunteers; moderate to severe

Outcome Measures

Primary Outcomes (1)

• Number of participants (Healthy Volunteers) with reported adverse events receiving multiple 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.

  21 days

Secondary Outcomes (11)

• Area under the concentration versus time curve within a dosing interval (AUC0-tau), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.

  Days 1-7 (dosing), post-dose (days 8-10).

• Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC0-t), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.

  Days 1-7 (dosing), post-dose (days 8-10).

• Area under the concentration versus time curve within a dosing interval (AUC0-inf), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.

  Day 7 only

• Maximum observed concentration (Cmax), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.

  Days 1-7 (dosing), post-dose (days 8-10).

• Apparent oral clearance (CL/F), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.

  Days 1-7 (dosing), post-dose (days 8-10).

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.

  Days 1-7 (dosing), post-dose (day 8).

Study Arms (4)

SKI-O-703 200 mg (once daily)

EXPERIMENTAL

SKI-O-703 capsule (1 x 200 mg)

Drug: SKI-O-703 capsule

SKI-O-703 400 mg (once daily)

EXPERIMENTAL

SKI-O-703 capsule (2 x 200 mg, once daily)

Drug: SKI-O-703 capsule

SKI-O-703 200 mg (twice daily)

EXPERIMENTAL

SKI-O-703 capsule (1 x 200 mg twice daily)

Drug: SKI-O-703 capsule

Placebo

PLACEBO COMPARATOR

Placebo capsule

Drug: Placebo capsule

Interventions

SKI-O-703 capsule DRUG

SKI-O-703 200 mg capsule with no inactive excipients.

SKI-O-703 200 mg (once daily); SKI-O-703 200 mg (twice daily); SKI-O-703 400 mg (once daily)

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 investigator to be in good health, as judged by absence of clinically significant diseases and clinically significant abnormal values as determined by detailed medical history review, complete physical examination, and clinical laboratory evaluations.
• Male subjects and female subjects of non-childbearing potential 18-55 years old, inclusive, at time of screening.
• Females of non-childbearing potential are those who have been surgically sterile for at least 6 months or who have been postmenopausal for at least 2 years and have follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status.
• Male subjects agree to use a condom with spermicide or to 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 pregnancy tests at screening and on Day -1.
• Body mass index between 18.0 and 30.0 kg/m2, inclusive, and body weight of ≥ 50 kg.
• Able to understand the study and any risks of 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 due to study participation, impact 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 of drugs.
• Any surgical or medical condition that could possibly affect drug absorption, distribution, metabolism, and excretion (e.g. bariatric procedure).
• Any medical/surgical procedure or trauma within 4 weeks prior to Day -1 as determined by the investigator.
• Any clinically significant infection within 3 months prior to Day -1 as determined by the investigator.
• Any of the following abnormal laboratory values upon repeat testing at Screening or Check-in (Day -1):
• Hemoglobin \< lower limit of normal (LLN),
• Platelet count \<LLN,
• Absolute neutrophil count \<LLN or \>upper limit of normal (ULN),
• Alanine aminotransferase or aspartate aminotransferase \>ULN,
• Creatinine or blood urea nitrogen \>ULN, or
• Any other clinically significant, in the opinion of the investigator, abnormal laboratory result.
• Use of concomitant medications from 30 days or 5 half-lives prior to Day -1 (whichever is longer) through completion of the End of Study (EOS) visit, including prescription medications, nutritional supplements, herbal remedies, and over-the-counter medications (note: use of vitamin supplements should be stopped at least 7 days prior to Screening through completion of the EOS visit).
• 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 through the EOS 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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 20, 2017
• Study Start: September 22, 2016
• Primary Completion: December 21, 2016
• Study Completion: December 21, 2016
• Last Updated: October 20, 2017

Record last verified: 2017-10

Locations

US (1)