A Phase 1, Randomized, Placebo-controlled, Double-blind, Multiple Ascending Dose Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral Doses of TCK-276 in Patients With Rheumatoid Arthritis
Overview
- Phase
- Phase 1
- Intervention
- TCK-276
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Teijin America, Inc.
- Enrollment
- 32
- Locations
- 8
- Primary Endpoint
- Number ot Participants With Treatment Emergent Adverse Events
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The study is to evaluate the safety, tolerability, and pharmacokinetic (PK) of multiple orally administered TCK-276 in both males and females with Rheumatoid Arthritis (RA).
Detailed Description
This is a Phase 1, multi-center, double-blind, randomized, placebo-controlled, multiple ascending dose (MAD) study. The study will consist of a Screening Visit (Days -1 to Day 10), Treatment duration (up to 11 days) and a Follow-up/end of treatment (EOT) visit. This MAD study will consist of 4 cohorts of 8 patients (6 active treatment and 2 matching placebo, or a 3:1 ratio), each receiving an oral dose of TCK-276 or matching placebo for 7 days (once daily (QD) under fed condition). The first cohort will be divided into 2 subgroups to implement the sentinel dosing approach. The study duration is approximately 42 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of RA and meeting the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA.
- •Patients between the ages of 18 and 64 years, inclusive, at the Screening Visit.
- •Female patient must be not pregnant, not breast feeding and one of the following conditions need to apply:
- •Of non-childbearing potential based on documented surgical treatment or post-menopausal, meaning patient had spontaneous amenorrhea for at least 12 months without alternate medical cause prior to Screening Visit and follicle stimulating hormone (FSH) \> 40 U/mL at the Screening Visit.
- •Of childbearing potential and using a highly effective method of contraception and agrees to remain on a highly effective method from the time of signing the informed consent form (ICF) until 21 days after the last dose.
- •Male patient must agree to stay abstinent or must use together with his female partner(s) a form of highly effective contraceptive (failure rate of \< 1% per year) from the time of signing the ICF until up to 3 months after the last dose of the study drug.
- •Nonsmokers (or other nicotine use) as determined by history and by negative urine cotinine concentration at the Screening Visit and at Admission.
- •Body mass index (BMI) between 18.5 and 32.0 kg/m2, inclusive, at the Screening Visit.
- •Patient is required to have completed a COVID-19 vaccine regimen within no more than 5 months prior to screening to be eligible for the study.
- •Permitted concomitant medications for any reason, must be on a stable dose.
Exclusion Criteria
- •Female patients who are breastfeeding or have a positive urine pregnancy test.
- •Patients who are unable to eat the prescribed meals during the stay at the site; vegetarian or vegan.
- •Patient has a history of significant drug allergy.
- •Patient has used a study drug, any prohibited medication(s), over-the-counter (OTC) medications, vitamins, dietary and herbal supplements.
- •Patient has a history of active suicidal ideation, or any psychiatric disorders that will affect the patient's ability to participate in the study.
- •Patient has a current or recent history of uncontrolled, clinically significant infectious, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
- •Patient with any of the laboratory abnormalities as per reference.
- •Patient has a history of alcohol and/or drug abuse within 24 weeks.
- •Patient has positive results for drug testing and breath alcohol test.
- •Regular consumption of alcohol within 6 months prior to the Screening Visit.
Arms & Interventions
Cohort 1
The patient will receive Dose A of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276
Cohort 1
The patient will receive Dose A of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276 Placebo
Cohort 2
The patient will receive Dose B of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276
Cohort 2
The patient will receive Dose B of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276 Placebo
Cohort 3
The patient will receive Dose C of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276
Cohort 3
The patient will receive Dose C of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276 Placebo
Cohort 4
The patient will receive Dose D of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276
Cohort 4
The patient will receive Dose D of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
Intervention: TCK-276 Placebo
Outcomes
Primary Outcomes
Number ot Participants With Treatment Emergent Adverse Events
Time Frame: 42 days (duration of study)
To evaluate the safety and tolerability of multiple oral doses of TCK-276 or placebo in patients with rheumatoid arthritis (RA)
Secondary Outcomes
- Metabolic Ratio (MR) for Cmax(Day 1 and Day 7)
- Fe 0-72: Percentage of Study Drug Excreted Unchanged in the Urine(Day 7 0-72 hours)
- Cmax: Plasma Concentrations of TCK-276 and TEI-W00595 (Metabolite)(Day 1 and Day 7)
- Tmax: Time of Maximum Plasma Concentration Determined Directly From the Concentration-time Profile(Day 1 and Day 7)
- t½: Terminal Elimination Half-life(Day 1 and Day 7)
- AUCtau: Area Under the Plasma Concentration-time Curve Over a Dosing Interval, Tau = 24 Hours(Day 1 and Day 7)
- AUC0-inf: Area Under the Plasma Concentration Time Curve From Pre-dose (Time 0) Extrapolated to Infinite Time(Day 1 and Day 7)
- Clearance (CL)/F: Apparent Total Body Clearance (Parent Only)(Day 1 and Day 7)
- Vz/F: Apparent Volume of Distribution Based on Terminal Phase (Parent Only)(Day 1 and Day 7)
- MRT0-inf: Mean Residence Time Extrapolated to Infinity(Day 1 and Day 7)
- Racc (Cmax): Accumulation Ratio Based on Cmax(Day 1 and Day 7)
- Racc (AUCtau): Accumulation Ratio Based on AUCtau(Day 1 and Day 7)
- MR for Area Under the Plasma Concentration-time Curve (AUC)Tau(Day 1 and Day 7)
- MR for Area Under the Plasma Concentration-time Curve (AUC)0-inf(Day 1 and Day 7)
- Ae 0-24: Amount of Study Drug Excreted Unchanged in the Urine (Days 1 and 7)(Day 1 and Day 7)
- Fe 0-24: Percentage of Study Drug Excreted Unchanged in the Urine (Days 1 and 7)(Day 1 and Day 7)
- Clearance Renal (CLr): Renal Clearance (Days 1 and 7)(Day 1 and Day 7)
- Ae 0-72: Amount of Study Drug Excreted Unchanged in the Urine (Day 7)(Day 7 0-72 hours)