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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02717988
• Date of registration: 04/03/2016
• Prospective Registration: No
• Primary sponsor: Oscotec Inc.
• Public title: Safety, Tolerability, and Pharmacokinetics of a Single Oral Dose of SKI-O-703 in Healthy Volunteers
• Scientific 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
• Date of first enrolment: September 2015
• Target sample size: 48
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02717988
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United States

Key inclusion & exclusion 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
- Platelet count
- Absolute neutrophil count 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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Placebo capsule

Drug: SKI-O-703 capsule

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

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]

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]

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]

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]

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

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]

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]

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]

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

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

Secondary ID(s)

OSCO-P1201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

PPD